256 results on '"Shivaprakash M. Rudramurthy"'
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2. Comparative fitness trade-offs associated with azole resistance in Candida auris clinical isolates
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Sourav Das, Shreya Singh, Yamini Tawde, Tushar K. Dutta, Shivaprakash M. Rudramurthy, Harsimran Kaur, Tushar Shaw, and Anup Ghosh
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Candida auris ,Fitness cost ,Multidrug resistance ,Oxidative stress ,Stress response ,Antifungal tolerance ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Multidrug-resistant yeast Candida auris is a serious threat to public health with documented survival in various hospital niches. The dynamics of this survival benefit and its trade off with drug resistance are still unknown for this pathogen. In this study we investigate the oxidative stress response (OSR) in fluconazole-resistant C. auris and compare its relative fitness with fluconazole-susceptible strains. A total of 351 C. auris clinical isolates (61 fluconazole-susceptible and 290 fluconazole-resistant) were screened for stress tolerance by spot assay and 95.08 % fluconazole-susceptible isolates were hyper-resistant to oxidative stress while majority (94.5 %) fluconazole-resistant isolates had lower oxidative tolerance. Expression of Hog1 and Cta1 gene transcript levels and cellular catalase levels were significantly higher in fluconazole-susceptible isolates and a corresponding higher intracellular reactive oxygen species level (iROS) was accumulated in the fluconazole-resistant isolates. Biofilm formation and cell viability under oxidative stress revealed higher biofilm formation and better viability in fluconazole-susceptible isolates. Fluconazole-resistant isolates had higher basal cell wall chitin. On comparison of virulence, the % cytotoxicity in A549 cell line was higher in fluconazole-susceptible isolates and the median survival of the infected larvae in G. mellonella infection model was higher in fluconazole-resistant (5; IQR:4.5–5 days) vs. fluconazole-susceptible C. auris (2; IQR:1.5–2.5 days). All organisms evolve with changes in their environmental conditions, to ensure an optimal balance between proliferation and survival. Development of tolerance to a certain kind of stress example antifungal exposure in yeast can leads to a compensatory decrease in tolerance for other stresses. This study provides useful insights into the comparative fitness and antifungal susceptibility trade off in C. auris. We report a negative association between H2O2 tolerance and fluconazole susceptibility. Using in-vitro cell cytotoxicity and in-vivo survival assays we also demonstrate the higher virulence potential of fluconazole-susceptible C. auris isolates corroborating the negative correlation between susceptibility and pathogen survival or virulence. These findings could also be translated to clinical practice by investigating the possibility of using molecules targeting stress response and fitness regulating pathways for management of this serious infection.
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- 2024
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3. Two promising Bacillus-derived antifungal lipopeptide leads AF4 and AF5 and their combined effect with fluconazole on the in vitro Candida glabrata biofilms
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Madduri Madhuri, Shivaprakash M. Rudramurthy, and Utpal Roy
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Antifungal lipopeptide ,Bacillus sp. ,biofilm inhibition ,Candida glabrata ,CV assay ,confocal microscopy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Introduction:Candida species are endowed with the ability to produce biofilms, which is one of the causes of pathogenicity, as biofilms protect yeasts from antifungal drugs. Candida glabrata (Nakaseomyces glabrata) is one of the most prevalent pathogenic yeasts in humans and a biofilm producer.Methods: The study was aimed at evaluating the combined effects of two highly promising antifungal biomolecules (AF4 and AF5) lipopeptide in nature, chromatographically purified to homogeneity from Bacillus subtilis (B. subtilis) and the standard antifungal fluconazole (at different concentrations) to demonstrate C. glabrata biofilm formation inhibition. Biofilm production and inhibition were evaluated by quantification of the biofilm biomass and metabolic activity using crystal violet (CV) staining and XTT reduction assays, respectively. Microscopic techniques such as confocal scanning laser microscopy (CSLM) and scanning electron microscopy (SEM) were employed to visualize biofilm formation and inhibition.Results and Discussion: Compared to untreated and fluconazole-treated biofilms, an enhanced in vitro anti-biofilm effect of the antifungal lipopeptides AF4/AF5 alone and their combinations with fluconazole was established. The lipopeptides AF4/AF5 alone at 8 and 16 μg/mL exhibited significant biomass and metabolic activity reductions. SEM and CSLM images provided evidence that the lipopeptide exposure results in architectural alterations and a significant reduction of C. glabrata biofilms, whereas (2′, 7′-dichlorofluorescin diacetate (DCFDA) and propidium iodide (PI) analyses showed reactive oxygen species (ROS) generation along with membrane permeabilization. The estimation of exopolysaccharides (EPS) in AF4/AF5-treated biofilms indicated EPS reduction. The combinations of fluconazole (64/128 μg/mL) and AF4/AF5 lipopeptide (16 μg/mL) were found to significantly disrupt the mature (24 h) biofilms as revealed by CSLM and SEM studies. The CSLM images of biofilms were validated using COMSTAT. The FTIR-analyses indicate the antibiofilm effects of both lipopeptides on 24 h biofilms to support CSLM and SEM observations. The combinations of fluconazole (64/128 μg/mL) and AF4/AF5 lipopeptide were found to disrupt the mature biofilms; the study also showed that the lipopeptides alone have the potentials to combat C. glabrata biofilms. Taken together, it may be suggested that these lipopeptide leads can be optimized to potentially apply on various surfaces to either reduce or nearly eradicate yeast biofilms.
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- 2024
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4. Scedosporium Infection in Recipients of Kidney Transplants from Deceased Near-Drowning Donor
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Devprakash Choudhary, Harsimran Kaur, Vanji Nathan Subramani, Smita Pattanaik, Shivakumar S. Patil, Jasmine Sethi, Manharpreet Kaur, Priya Sreenivasan, Sheetal Thakur, Parul Gupta, Arvind Sekar, Sarbpreet Singh, Muralidharan Jayashree, Deepesh Kenwar, Shivaprakash M. Rudramurthy, and Ashish Sharma
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fungi ,donor-derived fungal infection ,respiratory infections ,Scedosporium aurianticum ,pneumonia ,near-drowning organ donor ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.
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- 2023
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5. Isolated tracheal mucormycosis in diabetes mellitus and bronchoscopic management
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Vikram Damaraju, Ritesh Agarwal, Nidhi Prabhakar, Amanjit Bal, Shivaprakash M. Rudramurthy, and Valliappan Muthu
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Diseases of the respiratory system ,RC705-779 - Published
- 2024
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6. Clinical and Mycologic Characteristics of Emerging Mucormycosis Agent Rhizopus homothallicus
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Shivaprakash M. Rudramurthy, Shreya Singh, Rimjhim Kanaujia, Hansraj Chaudhary, Valliappan Muthu, Naresh Panda, Abhishek Pandey, Sheetal Thakur, Harsimran Kaur, Anup Ghosh, Ritesh Agarwal, and Arunaloke Chakrabarti
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Rhizopus homothallicus ,Rhizopus arrhizus ,mucormycosis ,fungi ,fungal infections ,COVID-19 associated mucormycosis ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02–0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03–16], itraconazole [0.03–16], posaconazole [0.03–8], and isavuconazole [0.03–16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.
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- 2023
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7. Two promising natural lipopeptides from Bacillus subtilis effectively induced membrane permeabilization in Candida glabrata
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Madhuri Madduri, Shivaprakash M. Rudramurthy, and Utpal Roy
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antifungal ,bioactive ,Bacillus subtilis ,Candida glabrata ,lipopeptides ,membrane permeabilization ,Biochemistry ,QD415-436 ,Organic chemistry ,QD241-441 ,Chemistry ,QD1-999 ,Science - Abstract
Candida glabrata is an important opportunistic human pathogen well known to develop resistance to antifungal drugs. Due to their numerous desirable qualities, antimicrobial lipopeptides have gained significant attention as promising candidates for antifungal drugs. In the present study, two bioactive lipopeptides (AF4 and AF5 m/z 1071.5 and 1085.5, respectively), coproduced and purified from Bacillus subtilis RLID12.1, consist of seven amino acid residues with lipid moieties. In our previous studies, the reversed phased-HPLC purified lipopeptides demonstrated broad-spectrum of antifungal activities against over 110 Candida albicans, Candida non-albicans and mycelial fungi. Two lipopeptides triggered membrane permeabilization of C. glabrata cells, as confirmed by propidium iodide-based flow cytometry, with PI uptake up to 99% demonstrating fungicidal effects. Metabolic inactivation in treated cells was confirmed by FUN-1-based confocal microscopy. Together, the results indicate that these lipopeptides have potentials to be developed into a new set of antifungals for combating fungal infections.
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- 2024
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8. Nucleic-Acid-Based Molecular Fungal Diagnostics: A Way to a Better Future
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Rajendra Gudisa, Ritika Harchand, and Shivaprakash M. Rudramurthy
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molecular diagnosis ,fungal infection ,point of care ,Medicine (General) ,R5-920 - Abstract
The world has seen a tremendous increase in the number of fungal infections during the past two decades. Recently, the World Health Organisation released the pathogen priority list for fungal infections, signifying the importance of these infections in the fields of research and public health. Microbiology laboratories demand an upgrade in the diagnostic system to keep up with the increased burden of these infections. Diagnosis of fungal infections using conventional techniques has always faced limitations in terms of specificity, sensitivity, and turnaround time. Although these methods are the core pillars of the diagnosis, there is an increased need for molecular approaches. Molecular techniques have revolutionised the field of fungal diagnostics. The diverse array of molecular techniques, including techniques like Polymerase Chain Reaction (PCR), have emerged as a cornerstone in fungal diagnostics. Molecular techniques have transformed fungal diagnostics, providing powerful tools for the rapid and accurate identification of pathogens. As these technologies continue to evolve, their integration into routine clinical practice holds the promise of improving patient outcomes through timely and targeted antifungal interventions. This review will cover the molecular approaches involved in fungal diagnostics, moving from the basic techniques to the advanced-level nucleic-acid-based molecular approaches providing a high throughput and decreased turnaround time for the diagnosis of serious fungal infections.
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- 2024
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9. A case control investigation of COVID-19 associated mucormycosis in India
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Tanu Anand, Aparna Mukherjee, Aanchal Satija, Poonam Sharma Velamuri, Kh. Jitenkumar Singh, Madhuchhanda Das, Kripa Josten, Pragya D. Yadav, Rima R. Sahay, Archana Y. Keche, Nitin M. Nagarkar, Prashant Gupta, D. Himanshu, Sejal N. Mistry, Jimy D. Patel, Prajwal Rao, Shalesh Rohatgi, Soumitra Ghosh, Avijit Hazra, Anupma Jyoti Kindo, Radha Annamalai, Shivaprakash M. Rudramurthy, Mini P. Singh, Mohammad Shameem, Nazish Fatima, Janakkumar R. Khambholja, Sangita Parikh, Manisha Madkaikar, Vandana D. Pradhan, Sushila Kataria, Pooja Sharma, Samiran Panda, and ICMR-Mucormycosis group
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Mucormycosis ,Satellite ,Epidemic ,Corticosteroids ,Diabetes ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case–control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. Methods Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. Results CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. Conclusions Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.
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- 2022
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10. Role of serum procalcitonin in the diagnosis and monitoring of treatment response in treatment-naïve subjects with chronic pulmonary aspergillosis
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Inderpaul Singh Sehgal, Sahajal Dhooria, Naresh Sachdeva, Shivaprakash M. Rudramurthy, Kuruswamy Thurai Prasad, Valliappan Muthu, Ashutosh Nath Aggarwal, Mandeep Garg, Arunaloke Chakrabarti, and Ritesh Agarwal
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Pulmonary tuberculosis ,Aspergilloma ,CCPA ,CFPA ,Pneumonia ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Background: Interferon-gamma (IFN-γ) down-regulates plasma procalcitonin (PCT), marker of inflammation. Chronic pulmonary aspergillosis (CPA) is associated with low IFN-γ levels. Thus, plasma PCT may be elevated in CPA and could have a role in diagnosing and monitoring treatment response in CPA. Herein, we investigate the diagnostic performance of plasma PCT in CPA. Methods: We extracted the demographic, clinical, radiological, treatment outcomes, and plasma PCT levels of CPA subjects and controls (previously treated pulmonary tuberculosis with radiological abnormalities on CT chest [diseased controls] and treatment naïve active pulmonary tuberculosis [PTB]). We treated CPA subjects with six months of oral itraconazole. We took 0.25 ng/mL as a cut-off value for PCT. The study’s primary objective was to ascertain the diagnostic performance of PCT in diagnosing CPA. The key secondary outcome was to study the change in the plasma PCT levels after itraconazole therapy. Results: We included 190 CPA cases and 40 controls (diseased controls [n = 20] and active PTB [n = 20]). PCT was elevated (≥0.25 ng/mL) in only 7 (3.7%) subjects with CPA. The sensitivity and specificity of PCT (≥0.25 ng/mL) were 3.7% (1.5–7.4%) and 100 (91.2–100%), respectively. The area under the curve for plasma PCT was 0.48 (95% confidence interval, 0.39–0.58). The plasma PCT values were available in 93 subjects at six months. There was a significant decline in the median plasma levels of PCT after treatment; however, the PCT levels either increased or remained the same in 45% of the subjects. Conclusion: Plasma procalcitonin has poor performance in diagnosing and following subjects with CPA.
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- 2023
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11. Directed Evolution Detects Supernumerary Centric Chromosomes Conferring Resistance to Azoles in Candida auris
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Aswathy Narayanan, Praveen Kumar, Anshu Chauhan, Mohit Kumar, Kusum Yadav, Atanu Banerjee, Ravi Datta Sharma, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, Kaustuv Sanyal, and Rajendra Prasad
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drug resistance ,experimental evolution ,extra chromosomes ,karyotype ,Microbiology ,QR1-502 - Abstract
ABSTRACT Candida auris exhibits resistance to multiple antifungal drug classes and sterilization agents, posing threats to the immunocompromised worldwide. Among the four major geographical clades, the East Asian clade 2 isolates of C. auris are mostly drug susceptible. In this study, we experimentally evolved one such drug-susceptible isolate for multiple generations in the presence of the antifungal compound fluconazole and analyzed changes in the karyotype, DNA sequence, and gene expression profiles in three evolved drug-resistant isolates. Next-generation sequencing and electrophoretic karyotyping confirm the presence of segmental aneuploidy as supernumerary chromosomes originating from centromere-inclusive chromosomal duplication events in two such cases. A 638-kb region and a 675-kb region, both of which originated from chromosome 5 and contained its centromere region, are instances of supernumerary chromosome formation identified in two evolved fluconazole-resistant isolates. Loss of the supernumerary chromosomes from the drug-resistant isolates results in a complete reversal of fluconazole susceptibility. Transcriptome analysis of the third isolate identified overexpression of drug efflux pumps as a possible non-aneuploidy-driven mechanism of drug resistance. Together, this study reveals how both aneuploidy-driven and aneuploidy-independent mechanisms may operate in parallel in an evolving population of C. auris in the presence of an antifungal drug, in spite of starting from the same strain grown under similar conditions, to attain various levels of fluconazole resistance. IMPORTANCE Fungal pathogens develop drug resistance through multiple pathways by acquiring gene mutations, increasing the copy number of genes, or altering gene expression. In this study, we attempt to understand the mechanisms of drug resistance in the recently emerged superbug, C. auris. One approach to studying this aspect is identifying various mechanisms operating in drug-resistant clinical isolates. An alternative approach is to evolve a drug-susceptible isolate in the presence of an antifungal compound and trace the changes that result in drug resistance. Here, we evolve a drug-susceptible isolate of C. auris in the laboratory in the presence of a widely used antifungal compound, fluconazole. In addition to the already known changes like overexpression of drug efflux pumps, this study identifies a novel mechanism of azole resistance by the emergence of additional chromosomes through segmental duplication of chromosomal regions, including centromeres. The centric supernumerary chromosome helps stable amplification of a set of genes with an extra copy to confer fluconazole resistance.
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- 2022
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12. Multicenter Epidemiologic Study of Coronavirus Disease–Associated Mucormycosis, India
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Atul Patel, Ritesh Agarwal, Shivaprakash M. Rudramurthy, Manoj Shevkani, Immaculata Xess, Ratna Sharma, Jayanthi Savio, Nandini Sethuraman, Surabhi Madan, Prakash Shastri, Deepak Thangaraju, Rungmei Marak, Karuna Tadepalli, Pratik Savaj, Ayesha Sunavala, Neha Gupta, Tanu Singhal, Valliappan Muthu, and Arunaloke Chakrabarti
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respiratory infections ,severe acute respiratory syndrome coronavirus 2 ,SARS-CoV-2 ,SARS ,COVID-19 ,coronavirus disease ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
During September–December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)–associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September–December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19–related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.
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- 2021
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13. Evaluation of environmental Mucorales contamination in and around the residence of COVID-19-associated mucormycosis patients
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Anup K. Ghosh, Ravinder Singh, Snigdha Reddy, Shreya Singh, Shivaprakash M. Rudramurthy, Harsimran Kaur, Hansraj Choudhary, and Arunaloke Chakrabarti
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COVID-19 associated mucormycosis (CAM) ,environmental mucorales ,air sampling ,amplified fragment length polymorphism (AFLP) ,genetic relatedness ,Microbiology ,QR1-502 - Abstract
IntroductionRecently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients’ residences.MethodsThe residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients’ residence and cultured on Dichloran Rose–Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients’ clinical isolates.ResultsThe median spore count (mean ± SD, cfu/m3) of Mucorales in the air of patients’ bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients’ residences. Rhizopus arrhizus was isolated from the environment of all patients’ residences (n = 25); other Mucorales species isolated were Cunninghamella bertholletiae (n = 14), Rhizopus microsporus (n = 6), Rhizopus delemar (n = 6), Syncephalastrum racemosum (n = 1), Lichtheimia corymbifera (n = 1), and Mucor racemosus (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients’ bedrooms and respective clinical isolates from patients.DiscussionThe study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients’ convalescence period and environmental decontamination could minimize exposure in those susceptible patients.
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- 2022
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14. Application of Novel Short Tandem Repeat Typing for Wickerhamomyces anomalus Reveals Simultaneous Outbreaks within a Single Hospital
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Bram Spruijtenburg, Shivaprakash M. Rudramurthy, Eelco F. J. Meijer, Merlijn H. I. van Haren, Harsimran Kaur, Arunaloke Chakrabarti, Jacques F. Meis, and Theun de Groot
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Wickerhamomyces anomalus ,Candida pelliculosa ,short tandem repeats ,genotyping ,whole-genome sequencing ,antifungal susceptibility testing ,Biology (General) ,QH301-705.5 - Abstract
Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.
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- 2023
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15. Comprehensive Taxonomical Analysis of Trichophyton mentagrophytes/interdigitale Complex of Human and Animal Origin from India
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Shivaprakash M. Rudramurthy, Dipika Shaw, Shamanth Adekhandi Shankarnarayan, Abhishek, and Sunil Dogra
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Trichophyton mentagrophytes ,phylogenetic analysis ,internal transcribed spacer ,translational elongation factors ,mating gene ,animal ,Biology (General) ,QH301-705.5 - Abstract
Taxonomic delineation of etiologic agents responsible for recalcitrant dermatophytosis causing an epidemic in India is still debated. The organism responsible for this epidemic is designated as T. indotineae, a clonal offshoot of T. mentagrophytes. To evaluate the real identity of the agent causing this epidemic, we performed a multigene sequence analysis of Trichophyton species isolated from human and animal origin. We included Trichophyton species isolated from 213 human and six animal hosts. Internal transcribed spacer (ITS) (n = 219), translational elongation factors (TEF 1-α) (n = 40), ß-tubulin (BT) (n = 40), large ribosomal subunit (LSU) (n = 34), calmodulin (CAL) (n = 29), high mobility group (HMG) transcription factor gene (n = 17) and α-box gene (n = 17) were sequenced. Our sequences were compared with Trichophyton mentagrophytes species complex sequences in the NCBI database. Except for one isolate (ITS genotype III) from animal origin, all the tested genes grouped our isolates and belonged to the “Indian ITS genotype”, currently labeled as T. indotineae. ITS and TEF 1-α were more congruent compared to other genes. In this study, for the first time, we isolated the T mentagrophytes ITS Type VIII from animal origin, suggesting the role of zoonotic transmission in the ongoing epidemic. Isolation of T. mentagrophytes type III only from animal indicates its niche among animals. Outdated/inaccurate naming for these dermatophytes in the public database has created confusion in using appropriate species designation.
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- 2023
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16. Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention
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Ranjot Kaur, Sarah R. Dennison, Andrea J. Burrow, Shivaprakash M. Rudramurthy, Rajan Swami, Varun Gorki, O. P. Katare, Anupama Kaushik, Bhupinder Singh, and Kamalinder K. Singh
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Pulmonary aspergillosis ,Voriconazole ,Inhalation ,Antifungal ,Hybrid nanoparticles ,Phospholipid ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract Background Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.e., dipalmitoylphosphatidylcholine and natural biodegradable polymer, i.e., chitosan, to augment its pulmonary deposition and retention, following nebulization. Results The developed nanosystem exhibited a particle size in the range of 228–255 nm and drug entrapment of 45–54.8%. Nebulized microdroplet characterization of NPs dispersion revealed a mean diameter of ≤ 5 μm, corroborating its deep lung deposition potential as determined by next-generation impactor studies. Biophysical interaction of LPH NPs with lipid-monolayers indicated their surface-active potential and ease of intercalation into the pulmonary surfactant membrane at the air-lung interface. Cellular viability and uptake studies demonstrated their cytocompatibility and time-and concentration-dependent uptake in lung-epithelial A549 and Calu-3 cells with clathrin-mediated internalization. Transepithelial electrical resistance experiments established their ability to penetrate tight airway Calu-3 monolayers. Antifungal studies on laboratory strains and clinical isolates depicted their superior efficacy against Aspergillus species. Pharmacokinetic studies revealed nearly 5-, 4- and threefolds enhancement in lung AUC, Tmax, and MRT values, construing significant drug access and retention in lungs. Conclusions Nebulized LPH NPs were observed as a promising solution to provide effective and safe therapy for the management of pulmonary aspergillosis infection with improved patient compliance and avoidance of systemic side-effects.
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- 2021
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17. Dynamics of in vitro development of azole resistance in Candida tropicalis
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Saikat Paul, Shreya Singh, Dipti Sharma, Arunaloke Chakrabarti, Shivaprakash M. Rudramurthy, and Anup K. Ghosh
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Candida tropicalis ,Experimentally induced ,Azole resistance ,Overexpression ,Mutation ,Microbiology ,QR1-502 - Abstract
Objectives: Increasing incidence of azole resistance in Candida tropicalis, especially to fluconazole, has been seen in Asian countries including India. Limited knowledge is available on the molecular mechanisms associated with the development of azole resistance in C. tropicalis. The present study examined the dynamics of in vitro azole resistance in C. tropicalis after prolonged treatment with fluconazole. Methods: Nine fluconazole-susceptible isolates of C. tropicalis were used in this study. Fluconazole resistance was induced experimentally in C. tropicalis isolates. The stability of induced resistance and cross-resistance to other azoles was examined. The molecular mechanisms of azole resistance were assessed by measuring the expression and mutation analysis of different genes. Results: Varying degrees of resistance [five with minimum inhibitory concentrations (MICs) ≤32 mg/L and four with MICs ≥128 mg/L] were noticed, and the resistance was developed in 3 months. Of the nine resistant isolates, four induced resistant isolates with MICs ≥128 mg/L presented temporal resistance stability up to 10 subcultures. These four isolates presented cross-resistance to other azoles and also an inducible overexpression of transporters (CDR1, CDR2, CDR3 and MDR1), ergosterol biosynthesis pathway genes (ERG1, ERG2, ERG3 and ERG11), transcription factors (TAC1 and UPC2) and stress-responsive genes (HSP90 and MKC1) was noticed. No mutations were seen in any of the four genes (ERG1, ERG3, ERG11 and UPC2) tested. Conclusions: Candida tropicalis isolates adapt themselves in the presence of continuous drug exposure and switch back to being susceptible in the absence of the drug. The acquisition of resistance in C. tropicalis is mediated by the overexpression of different resistance-related genes without any molecular alterations.
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- 2020
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18. The Comparative Evaluation of the Fujifilm Wako β-Glucan Assay and Fungitell Assay for Diagnosing Invasive Fungal Disease
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Shreya Singh, Rimjhim Kanaujia, Sourav Agnihotri, Harsimran Kaur, Arunaloke Chakrabarti, and Shivaprakash M. Rudramurthy
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1,3-β-d-glucan ,invasive fungal disease ,invasive aspergillosis ,invasive candidiasis ,fungal biomarker ,Fujifilm Wako assay ,Biology (General) ,QH301-705.5 - Abstract
Serum 1,3-β-d-glucan(BDG) is a broad fungal biomarker for invasive fungal disease (IFD). More data is still required to support the Fujifilm Wako assay as a valuable alternative to the widely used Fungitell assay. We included archived serum samples from 157 individuals (97 cases; 33-IA, 64-IC, and 60 controls) for the comparative performance evaluation of the Fungitell assay and the Fujifilm Wako assay for IFD diagnosis. The BDG value was significantly higher in patients with IFD vs. controls (70.79 pg/mL vs. 3.03 pg/mL, p: 0.0002). An area under the curve (AUC) for the IFD, IC, and IA diagnosis was 0.895, 0.910, and 0.866, respectively, for the Fujifilm Wako assay. Based on the highest Youden’s index (0.667), a cutoff of 5 pg/mL was selected as the optimum for the Fujifilm Wako assay with good sensitivity (79.4%), specificity (88.3%) and agreement (84.7%, Cohen’s k:0.691) with the Fungitell assay. The mean run-time of the Fujifilm Wako assay was 70.12 min, and real-time observation allowed earlier time to result in Fujifilm Wako vs. Fungitell assay (37 vs. 120 min, p: < 0.0001). Thus, our findings support the diagnostic value of the Fujifilm Wako assay for the diagnosis of IFD. However, there is still a need to validate diagnostic protocols to optimize their use in multi-centre studies with different patient groups.
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- 2022
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19. Ring-Modified Histidine-Containing Cationic Short Peptides Exhibit Anticryptococcal Activity by Cellular Disruption
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Komal Sharma, Shams Aaghaz, Indresh Kumar Maurya, Shreya Singh, Shivaprakash M. Rudramurthy, Vinod Kumar, Kulbhushan Tikoo, and Rahul Jain
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iodinated histidines ,membrane active peptides ,anticryptococcal activity ,iodopeptides ,pore formation ,cell lysis ,Organic chemistry ,QD241-441 - Abstract
Delineation of clinical complications secondary to fungal infections, such as cryptococcal meningitis, and the concurrent emergence of multidrug resistance in large population subsets necessitates the need for the development of new classes of antifungals. Herein, we report a series of ring-modified histidine-containing short cationic peptides exhibiting anticryptococcal activity via membrane lysis. The N-1 position of histidine was benzylated, followed by iodination at the C-5 position via electrophilic iodination, and the dipeptides were obtained after coupling with tryptophan. In vitro analysis revealed that peptides Trp-His[1-(3,5-di-tert-butylbenzyl)-5-iodo]-OMe (10d, IC50 = 2.20 μg/mL; MIC = 4.01 μg/mL) and Trp-His[1-(2-iodophenyl)-5-iodo)]-OMe (10o, IC50 = 2.52 μg/mL; MIC = 4.59 μg/mL) exhibit promising antifungal activities against C. neoformans. When administered in combination with standard drug amphotericin B (Amp B), a significant synergism was observed, with 4- to 16-fold increase in the potencies of both peptides and Amp B. Electron microscopy analysis with SEM and TEM showed that the dipeptides primarily act via membrane disruption, leading to pore formation and causing cell lysis. After entering the cells, the peptides interact with the intracellular components as demonstrated by confocal laser scanning microscopy (CLSM).
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- 2022
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20. Mucormycosis caused by Syncephalastrum spp.: Clinical profile, molecular characterization, antifungal susceptibility and review of literature
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Shreya Singh, Nupur Pal, Jagdish Chander, Raman Sardana, Bella Mahajan, Noyal Joseph, Arunaloke Chakrabarti, Shivaprakash M. Rudramurthy, P. Hariprasath, Saikat Paul, Harsimran Kaur, and Anup Ghosh
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Syncephalastrum racemosum ,Syncephalastrum monosporum ,MALDI -TOF MS ,Molecular ,Clinical infections ,Antifungal susceptibility ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: The clinical profile, molecular characteristics and antifungal susceptibility patterns of the Mucoraceous mould, Syncephalastrum spp are poorly characterized. The present study provides a comprehensive overview of these aspects of this rare fungus. Methods: We characterized 8 clinical isolates of Syncephalestrum spp by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), 28S rDNA sequencing, Amplified Fragment Length Polymorphism (AFLP, n = 7) and in-vitro antifungal susceptibility testing. Clinical details of these eight cases were reviewed with all cases of Syncephalestrum infections reported in the literature till August 2020. Results: S. racemosum (n = 4) and S. monosporum (n = 4) were identified by MALDI-TOF, sequencing and AFLP also clearly differentiated the two. All isolates were uniformly susceptible to amphotericin B and terbinafine. Analysis of clinical details in our eight patients with 43 more cases reported in the literature revealed that most of the reports were (78.4%) from India and cutaneous mucormycosis was the most common (37.3%) presentation followed by rhino-orbito-cerebral (23.5%) and pulmonary(17.6%) infection. Association of trauma with skin infection (p:0.042); immunosuppression/steroid use (p:0.005) and neutropenia (p:0.000) with pulmonary infection was seen. Conclusion: S. racemosum, S. monosporum give rise to human infections. The improved database of MALDI-TOF could distinguish the two species. Such rare and emerging infections merit careful consideration and clinical attention.
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- 2021
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21. Clinical Spectrum, Molecular Characterization, Antifungal Susceptibility Testing of Exophiala spp. From India and Description of a Novel Exophiala Species, E. arunalokei sp. nov
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Shreya Singh, Shivaprakash M. Rudramurthy, Arvind A. Padhye, Basavaraj M. Hemashetter, Ranganathan Iyer, Vinaykumar Hallur, Anuradha Sharma, Sourav Agnihotri, Sunita Gupta, Anup Ghosh, and Harsimran Kaur
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Exophiala ,India ,molecular ,novel species ,antifungal susceptibility ,Microbiology ,QR1-502 - Abstract
IntroductionExophiala spp. are important opportunist pathogens causing subcutaneous or even fatal disseminated infections in otherwise both immunosuppressed and healthy individuals but there are no systematic studies on the isolates of Exophiala species from India.MethodsTwenty-four isolates of Exophiala species were retrieved from the National Culture Collection of Pathogenic Fungi (NCCPF) and identified phenotypically and by molecular methods (ITS region sequencing) followed by antifungal susceptibility testing (AFST) as per CLSI-M38A3 guidelines. A review of the literature of cases from India was performed up to 1st January 2021 using the Medline and Cochrane database.ResultsE. dermatitidis (n = 8), E. jeanselmei (n = 6), E. spinifera (n = 6), E. mesophila (n = 1), E. oligosperma (n = 1), E. xenobiotica (n = 1) were identified and the sequencing of ITS, β-tubulin and β-actin revealed a novel species, E. arunalokei sp. nov. (n = 1). The ITS sequence phylogram of E. jeanselmei revealed that the majority (83%) formed a separate cluster close to type A while majority (75%) of E. dermatitidis were type B. The MIC50 (mg/L) of amphotericin, itraconazole, voriconazole, micafungin, caspofungin, anidulafungin, and posaconazole, was 1, 0.25, 0.125, 0.12, 0.125, 0.062, and 0.062, respectively. Sixteen more cases were identified on the literature review and a significant association of E. dermatitidis with history of surgical procedures (p = 0.013), invasive disease (p = 0.032) and of E. mesophila with tuberculosis (p = 0.026) was seen.ConclusionThis, to the best of our knowledge is the first study from India elucidating the molecular and clinical characteristics of Exophiala species and the first Indian report of human infection due to E. xenobiotica and E. arunalokei.
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- 2021
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22. Functional and Comparative Analysis of Centromeres Reveals Clade-Specific Genome Rearrangements in Candida auris and a Chromosome Number Change in Related Species
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Aswathy Narayanan, Rakesh Netha Vadnala, Promit Ganguly, Pavitra Selvakumar, Shivaprakash M. Rudramurthy, Rajendra Prasad, Arunaloke Chakrabarti, Rahul Siddharthan, and Kaustuv Sanyal
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Microbiology ,QR1-502 - Abstract
Candida auris
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- 2021
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23. Expression and Purification along with Evaluation of Serological Response and Diagnostic Potential of Recombinant Sap2 Protein from C. parapsilosis for Use in Systemic Candidiasis
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Manisha Shukla, Pankaj Chandley, Harsimran Kaur, Anup K. Ghosh, Shivaprakash M. Rudramurthy, and Soma Rohatgi
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Sap2 ,C. parapsilosis ,antibody ,ELISA ,systemic candidiasis ,diagnosis ,Biology (General) ,QH301-705.5 - Abstract
Systemic candidiasis is the fourth most common bloodstream infection in ICU patients worldwide. Although C. albicans is a predominant species causing systemic candidiasis, infections caused by non-albicans Candida (NAC) species are increasingly becoming more prevalent globally along with the emergence of drug resistance. The diagnosis of systemic candidiasis is difficult due to the absence of significant clinical symptoms in patients. We investigated the diagnostic potential of recombinant secreted aspartyl proteinase 2 (rSap2) from C. parapsilosis for the detection of Candida infection. The rSap2 protein was successfully cloned, expressed and purified using Ni-NTA chromatography under denaturing conditions using an E. coli-based prokaryotic expression system, and refolded using a multi-step dialysis procedure. Structural analysis by CD and FTIR spectroscopy revealed the refolded protein to be in its near native conformation. Immunogenicity analysis demonstrated the rSap2 protein to be highly immunogenic as evident from significantly high titers of Sap2-specific antibodies in antigen immunized Balb/c mice, compared to sham-immunized controls. The diagnostic potential of rSap2 protein was evaluated using immunoblotting and ELISA assays using proven candidiasis patient serum and controls. Immunoblotting results indicate that reactivity to rSap2 was specific to candidiasis patient sera with no cross reactivity observed in healthy controls. Increased levels of anti-Sap2-specific Ig, IgG and IgM antibodies were observed in candidiasis patients compared to controls and was similar in sensitivity obtained when whole Candida was used as coating antigen. In summary, the rSap2 protein from C. parapsilosis has the potential to be used in the diagnosis of systemic candidiasis, providing a rapid, convenient, accurate and cost-effective strategy.
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- 2021
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24. Molecular Typing and Antifungal Susceptibility of Candida viswanathii, India
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Shamanth A. Shankarnarayan, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, Dipika Shaw, Saikat Paul, Nandini Sethuraman, Harsimran Kaur, and Anup K. Ghosh
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Candida viswanathii ,fluconazole resistance ,invasive candidiasis ,emerging fungal infection ,molecular typing ,fungi ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report invasive candidiasis caused by Candida viswanathii over 2 time periods during 2013–2015 in a tertiary care hospital in Chandigarh, India. Molecular typing revealed multiple clusters of the isolates. We detected high MICs for fluconazole in the second time period.
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- 2018
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25. Systemic cryptococcosis in an immune-competent child
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Arushi G. Saini, Sooraj Patil, Triptee Agrawal, Aseem Basha, Rashi Garg, Shivaprakash M. Rudramurthy, Pankaj Vaidya, Akshay Saxena, and Pratibha Singhi
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Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Crytococcus neoformans is an encapsulated yeast that frequently affects immune-compromised patients, although increasingly being detected in the immune-competent host as well. We report a case of disseminated cryptococcosis in a young child in whom no immune deficiency was yet identified. A 4-year-old child presented with high-grade fever, intermittent abdominal pain and generalized skin eruptions for the past two months. He had pallor, firm lymphadenopathy, skin lesions with scarring and firm hepatosplenomegaly. Magnetic resonance imaging of brain and bone-marrow aspiration were normal. Fine-needle-aspiration-cytology of cervical lymph nodes demonstrated Cryptococcus. Serum latex-agglutination test showed a positive titer (1:256). Cryptococcus culture was sterile. The patient received intravenous liposomal amphotericin-B and oral flucytosine for 8 weeks followed by oral fluconazole. Disseminated cryptococcosis with involvement of reticuloendothelial and dermatological systems is rare. Early diagnosis and timely management of associated complications would be life saving. Keywords: Disseminated cryptococcosis, Skin infection, Lymph node, Cryptococcus
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- 2018
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26. ABC Transporter Genes Show Upregulated Expression in Drug-Resistant Clinical Isolates of Candida auris: A Genome-Wide Characterization of ATP-Binding Cassette (ABC) Transporter Genes
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Mohd Wasi, Nitesh Kumar Khandelwal, Alexander J. Moorhouse, Remya Nair, Poonam Vishwakarma, Gustavo Bravo Ruiz, Zoe K. Ross, Alexander Lorenz, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, Andrew M. Lynn, Alok K. Mondal, Neil A. R. Gow, and Rajendra Prasad
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Candida auris ,multidrug resistance ,ABC proteins ,drug efflux pumps ,fluconazole ,Microbiology ,QR1-502 - Abstract
ATP-binding cassette (ABC) superfamily members have a key role as nutrient importers and exporters in bacteria. However, their role as drug exporters in eukaryotes brought this superfamily member to even greater prominence. The capacity of ABC transporters to efflux a broad spectrum of xenobiotics represents one of the major mechanisms of clinical multidrug resistance in pathogenic fungi including Candida species. Candida auris, a newly emerged multidrug-resistant fungal pathogen of humans, has been responsible for multiple outbreaks of drug-resistant infections in hospitals around the globe. Our study has analyzed the entire complement of ABC superfamily transporters to assess whether these play a major role in drug resistance mechanisms of C. auris. Our bioinformatics analyses identified 28 putative ABC proteins encoded in the genome of the C. auris type-strain CBS 10913T; 20 of which contain transmembrane domains (TMDs). Quantitative real-time PCR confirmed the expression of all 20 TMD transporters, underlining their potential in contributing to the C. auris drug-resistant phenotype. Changes in transcript levels after short-term exposure of drugs and in drug-resistant C. auris isolates suggested their importance in the drug resistance phenotype of this pathogen. CAUR_02725 orthologous to CDR1, a major multidrug exporter in other yeasts, showed consistently higher expression in multidrug-resistant strains of C. auris. Homologs of other ABC transporter genes, such as CDR4, CDR6, and SNQ2, also displayed raised expression in a sub-set of clinical isolates. Together, our analysis supports the involvement of these transporters in multidrug resistance in C. auris.
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- 2019
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27. Parathyridaria percutanea and Subcutaneous Phaeohyphomycosis
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Shivaprakash M. Rudramurthy, Megha Sharma, Nandini Sethuraman, Pinaki Dutta, Bansidhar Tarai, Jayanthi Savio, Amanjit Bal, Usha Kalawat, and Arunaloke Chakrabarti
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nonsporulating fungi ,dematiaceous fungi ,Pleosporales ,Parathyridaria percutanea ,phaeohyphomycosis ,fungi ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Parathyridaria percutanea is an emerging fungus causing subcutaneous phaeohyphomycoses in renal transplant recipients in India. We identified P. percutanea from a patient with subcutaneous phaeohyphomycosis. From our culture collection, we identified the same fungus from 4 similar patients. We found 5 cases previously described in literature.
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- 2019
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28. Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management
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Shivaprakash M. Rudramurthy, Raees A. Paul, Arunaloke Chakrabarti, Johan W. Mouton, and Jacques F. Meis
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invasive aspergillosis ,Aspergillus flavus ,epidemiology ,molecular typing ,azole resistance ,amphotericin B resistance ,treatment ,epidemiological cut-off value ,Biology (General) ,QH301-705.5 - Abstract
Aspergillus flavus is the second most common etiological agent of invasive aspergillosis (IA) after A. fumigatus. However, most literature describes IA in relation to A. fumigatus or together with other Aspergillus species. Certain differences exist in IA caused by A. flavus and A. fumigatus and studies on A. flavus infections are increasing. Hence, we performed a comprehensive updated review on IA due to A. flavus. A. flavus is the cause of a broad spectrum of human diseases predominantly in Asia, the Middle East, and Africa possibly due to its ability to survive better in hot and arid climatic conditions compared to other Aspergillus spp. Worldwide, ~10% of cases of bronchopulmonary aspergillosis are caused by A. flavus. Outbreaks have usually been associated with construction activities as invasive pulmonary aspergillosis in immunocompromised patients and cutaneous, subcutaneous, and mucosal forms in immunocompetent individuals. Multilocus microsatellite typing is well standardized to differentiate A. flavus isolates into different clades. A. flavus is intrinsically resistant to polyenes. In contrast to A. fumigatus, triazole resistance infrequently occurs in A. flavus and is associated with mutations in the cyp51C gene. Overexpression of efflux pumps in non-wildtype strains lacking mutations in the cyp51 gene can also lead to high voriconazole minimum inhibitory concentrations. Voriconazole remains the drug of choice for treatment, and amphotericin B should be avoided. Primary therapy with echinocandins is not the first choice but the combination with voriconazole or as monotherapy may be used when the azoles and amphotericin B are contraindicated.
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- 2019
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29. Trend of pediatric cryptococcosis in a tertiary care centre and review of literature
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Harsimran Kaur, Parakriti Gupta, Rakesh Pilania, Deepti Suri, Surjit Singh, Anup Ghosh, and Shivaprakash M. Rudramurthy
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Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,Immunology and Microbiology (miscellaneous) ,Immunology ,Immunology and Allergy ,Microbiology - Abstract
Cryptococcosis is one of the most significant systemic fungal infections worldwide. Epidemiological data for pediatric cryptococcosis is very limited. Therefore, we planned this study to determine the burden of cryptococcosis in the pediatric population at our tertiary care center and performed review of literature.In this retrospective study, all the patients less than 18 years of age were diagnosed with cryptococcosis, from January 2015-June 2021 were included. Demographic, clinical, and laboratory details of all the patients were noted. Furthermore, PubMed and MedLine databases were comprehensively searched for cases of pediatric cryptococcosis till June 2021.Of the total 5420 samples from suspected cryptococcosis cases processed at mycology laboratory, a total of 21 episodes of cryptococcosis (0.39%) were identified in 15 pediatric patients. The majority of the patients were apparently immunocompetent (10/15). Central nervous system (CNS) cryptococcosis was the most common presentation, followed by disseminated disease. All the isolates were identified as Cryptococcus neoformans (formerly referred to as C. neoformans var grubii), except one that was identified as Papiliotrema laurentii (formerly referred to as Cryptococcus laurentii). A standard treatment regimen inclusive of induction and maintenance therapy was provided in only five patients. The literature review revealed a total of 125 studies describing 1134 cases, of which 76.4% are reported from outside Asia, the majority (65.7%) restricted to CNS with C. neoformans as the commonest species. The management profile divulged a significantly higher use of standard drug regimen in Asia as compared to the rest of the world. Mortality of 13.32% was noted worldwide.To the best of our knowledge, this is the first clinico-epidemiological study of pediatric cryptococcosis from India and the largest retrospective study worldwide. The rising incidence among immunocompetent individuals, especially in Asia, is a matter of concern. Clinical suspicion and early diagnosis are the cornerstones for the management of cases.
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- 2023
30. Clinical utility of time to positivity of blood cultures in cases of fungaemia: A prospective study
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Harsimran Kaur, Rimjhim Kanaujia, Shreya Singh, Kamal Kajal, Muralidharan Jayashree, Nitin James Peter, Shristi Verma, Mantavya Gupta, Pallab Ray, Anup Ghosh, Ram Samujh, and Shivaprakash M. Rudramurthy
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Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,Immunology and Microbiology (miscellaneous) ,Immunology ,Immunology and Allergy ,Microbiology - Abstract
Fungaemia due to yeast is a major cause of morbidity and mortality in critically ill patients. Although, automated blood cultures have improved the time to diagnosis, very few studies have systematically evaluated the utility of blood culture time to positivity (TTP) of fungaemia in the clinical scenario. In this study, we evaluated the TTP for different yeast species to determine its clinical utility.A prospective study including 244 consecutive patients admitted to the adult (n = 76) and paediatric (n = 168) intensive care units (ICUs) was conducted between December 2017 through March 2019. The clinical and demographic characteristics, BACTEC blood culture results and TTP for yeast positive blood cultures were recorded for analysis.A total of 244 patients with 357 episodes of candidaemia were enrolled during the study period. The TTP (mean ± SD) for all yeast species was 26.8 ± 23.6 h while it was significantly longer in paediatric than adult patients (30.5 ± 24.7 vs. 25.2 ± 22.9 h; p = 0.0001). Wickerhamomyces anomalus and Cyberlindnera jadinii (previously C. utilis) were exclusively isolated from paediatric population where W. anomalus demonstrated significantly longer TTP than C. jadinii. Among adult cases, C. albicans exhibited significantly longer TTP than C. tropicalis. In paediatric cases,80% of C. tropicalis and C. utilis flagged positive in blood culture before 24 h while majority (65.9%) of W. anomalus isolates flagged positive later than 24 h. Similarly in adult samples, 63% of C. tropicalis isolates beeped positive before 24 h.TTP for yeast may provide insight regarding the responsible yeast species before final identification among critical patients with candidaemia. Larger studies are warranted for evaluating clinical utility of TTP considering other complex factors like yeast burden, generation time, virulence and host factors, which may affect TTP.
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- 2023
31. Synthetic amino acids‐based short amphipathic peptides exhibit antifungal activity by targeting cell membrane disruption
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Shams Aaghaz, Komal Sharma, Indresh K. Maurya, Shivaprakash M. Rudramurthy, Shreya Singh, Vinod Kumar, Kulbhushan Tikoo, and Rahul Jain
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Drug Discovery - Published
- 2023
32. First case report of recurrent cervical lymphadenopathy due to Chordomyces antarcticum
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Vinaykumar Hallur, Rumita Dey, Mukund Sable, Shivaprakash M Rudramurthy, and Anupam Dey
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Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,Immunology and Microbiology (miscellaneous) ,Immunology ,Immunology and Allergy ,Microbiology - Published
- 2023
33. Correlation of plasma levels of itraconazole with treatment response at 4 weeks in chronic dermatophytosis: Results of a randomised controlled trial
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Hitesh Bhalavi, Dipika Shaw, Hitaishi Mehta, Tarun Narang, Naresh Sachdeva, Nusrat Shafiq, Shivaprakash M. Rudramurthy, and Sunil Dogra
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Infectious Diseases ,Dermatology ,General Medicine - Abstract
Itraconazole in varying doses and duration is being frequently used for the management of dermatophytosis. There is a scarcity of studies on the bioavailability of various itraconazole brands available in the market.The aim of this study was to determine the plasma concentration of itraconazole of various brands and its correlation with clinical efficacy in chronic dermatophytosis.One hundred patients with chronic dermatophytosis with age18 years were studied at the outpatient clinic of our tertiary care hospital. Plasma itraconazole level was estimated on Week 2 and Week 4 after randomly dividing the patients into Groups A, B and C who received cap itraconazole 100 mg twice a day of innovator, multinational and local generic brands, respectively, for 4 weeks. Both efficacy (cure, partial cure or no cure), safety and recurrence were compared between the three groups.At 4 weeks, number of patients classified as 'cured' were 10/26 (38.4%) in Group A, 5/22 in Group B (22.7%) and 3/21 (14.2%) in Group C (p = .002). Mycological cure rates at Week 4 in Groups A, B and C were 21 (80.8%), 17 (81.0%) and 5 (26.3%), respectively (p = .006). Plasma levels of itraconazole were comparable between the three groups at Week 2 and Week 4. No statistically significant correlation was found between itraconazole levels and treatment response in any of the groups at 4 weeks. Incidence of adverse effects and recurrence rates was also similar among the three groups.Cure rates for chronic dermatophytosis were poor with all three itraconazole brands at 4 weeks of treatment. Higher cure rates were obtained with innovator drug as compared to multinational and local generic brands at 4 weeks. Plasma levels of the three drugs were however similar, indicating that factors other than serum bioavailability are at play in determining response of chronic dermatophyte infections to oral itraconazole.
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- 2022
34. Antifungal prescription practices and consumption in a tertiary care hospital of a developing country
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Harsimran Kaur, Sivanantham Krishnamoorthi, Navneet Dhaliwal, Manisha Biswal, Shreya Singh, Valliappan Muthu, Shivaprakash M. Rudramurthy, Ritesh Agarwal, Sushmita Ghoshal, Surjit Singh, Pankaj Malhotra, Sanjay Jain, Ram Samujh, Anup Ghosh, and Arunaloke Chakrabarti
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Adult ,Tertiary Care Centers ,Antifungal Agents ,Prescriptions ,Infectious Diseases ,Amphotericin B ,Humans ,Voriconazole ,Dermatology ,General Medicine ,Child ,Developing Countries ,Fluconazole - Abstract
Antifungal stewardship is a less explored component of antimicrobial stewardship programmes, especially in developing countries.We aimed to determine antifungal prescription practices in a tertiary centre of a developing country to identify the challenges for antifungal stewardship programmes.Four single-day point prevalent surveys were performed in inpatient units and data were collected from medical records. Antifungal use was recorded in terms of consumption, therapeutic strategies and appropriateness.We found a 2.42%-point prevalence of antifungal prescriptions. Antifungal use was higher in children than adults (4.1% vs. 2.03%), medical than surgical units (3.7% vs. 1.24%) and ICUs than general wards (5.8% vs. 1.9%). The highest antifungal use was observed in the haematology-oncology units (29.3%) followed by emergency (16.2%) and gastroenterology units (11.6%). Among 215 prescriptions, amphotericin B was the most commonly prescribed (50.2%) followed by fluconazole (31.6%). The targeted antifungal therapy was practised more commonly (31.5%) than empiric (29.1%), pre-emptive (22.6%) and prophylactic (16.8%) therapy. Amphotericin B was commonly used for pre-emptive (p = .001) and targeted (p = .049) therapy, while fluconazole (p = .001) and voriconazole (p = .011) for prophylaxis. The prescriptions were inappropriate in 25.1% due to the wrong choice of antifungal (44.4%), indication (27.7%) and dosage (24%). The overall mean antifungal consumption was 2.71 DDD/1000 PD and 8.96 DOT/1000 PD.We report here the low prevalence of antifungal use at a tertiary care centre in a developing country. Though training for antifungal use would be important for antifungal stewardship, the challenge would remain with the affordability of antifungals.
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- 2022
35. Application of Novel Short Tandem Repeat Typing for Wickerhamomyces anomalus Reveals Simultaneous Outbreaks within a Single Hospital
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Groot, Bram Spruijtenburg, Shivaprakash M. Rudramurthy, Eelco F. J. Meijer, Merlijn H. I. van Haren, Harsimran Kaur, Arunaloke Chakrabarti, Jacques F. Meis, and Theun de
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Wickerhamomyces anomalus ,Candida pelliculosa ,short tandem repeats ,genotyping ,whole-genome sequencing ,antifungal susceptibility testing ,outbreak investigation - Abstract
Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.
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- 2023
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36. Aspergillosis: an Update on Clinical Spectrum, Diagnostic Schemes, and Management
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Rimjhim Kanaujia, Shreya Singh, and Shivaprakash M. Rudramurthy
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Infectious Diseases - Published
- 2023
37. Rapidly progressive lung coinfection due to Rhizopus and Scedosporium in a diabetic marijuana smoker
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Rimjhim, Kanaujia, Valliappan, Muthu, Shreya, Singh, Shivaprakash M, Rudramurthy, and Harsimran, Kaur
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Microbiology (medical) ,Infectious Diseases ,General Medicine - Published
- 2023
38. Faster and accurate identification of clinically important Trichosporon using MALDI TOF MS
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Abhila Parashar, Vijaylatha Rastogi, Shivaprakash M. Rudramurthy, Anup Kumar Ghosh, Jagdish Chander, and Anupma Jyoti Kindo
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Microbiology (medical) ,Infectious Diseases ,Mycoses ,Trichosporon ,General Immunology and Microbiology ,Immunology and Microbiology (miscellaneous) ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Immunology ,Humans ,Immunology and Allergy ,Microbiology - Abstract
Trichosporon species are emerging human pathogens, accounting for the second most common cause of non-candidal mycosis. Rapid and reliable identification of these agents allows a better understanding of their epidemiology and therapeutic management. The Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) technique has the potential to be precise, fast and cost-effective. However, the precision of identification totally depends upon the type of protein extraction method used and embedded database in the system. Our objectives were to standardize the protein extraction technique and expand the present Bruker database by creating an in-house database and validating it with diverse clinical Trichosporon species of Indian origin.Two different protein extraction protocols (on-plate and off-plate) were evaluated. The off-plate protocol was finalized for the identification. MALDI TOF MS with the existing Bruker database was evaluated for its ability to identify a total of 79 intergenic spacer 1 (IGS1) gene sequence confirmed clinical isolates of 5 different Trichosporon species.As outcome, off plate protocol yielded higher accuracy (73% on the species level and 95% on the genus level) than on-plate (25% on the genus level) in terms of log scores. The existing database for Trichosporon species was enriched with 28 sequence confirmed isolates, which improved accuracy from 73% to 100% and were identified up to species level with a log score2.3.Used with standardized protein-extraction protocol along with an expanded database, MALDI-TOF MS could be a rapid and reliable approach to identify clinical Trichosporon species routinely in the laboratory.
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- 2022
39. The minimal important difference of Saint George’s Respiratory Questionnaire in subjects with chronic pulmonary aspergillosis
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Inderpaul Singh Sehgal, Sahajal Dhooria, Valliappan Muthu, Kuruswamy Thurai Prasad, Ashutosh Nath Aggarwal, Arunaloke Chakrabarti, Shivaprakash M Rudramurthy, and Ritesh Agarwal
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Infectious Diseases ,General Medicine - Abstract
The estimates of the minimal important difference (MID) for the Saint George’s Respiratory Questionnaire (SGRQ) score in chronic pulmonary aspergillosis (CPA) remain unknown. We performed a retrospective analysis on treatment-naïve CPA subjects (n = 148) treated with 6-month oral itraconazole therapy and completed SGRQ at baseline and 6 months. The study’s objective was to estimate the MID for SGRQ. We used an anchor-based method to determine the MID and found the MID for SGRQ of 7.3.
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- 2023
40. Functional Characterization of a Bacillus -Derived Novel Broad-Spectrum Antifungal Lipopeptide Variant against Candida tropicalis and Candida auris and Unravelling Its Mode of Action
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Swetha Ramesh, Madhuri Madduri, Shivaprakash M. Rudramurthy, and Utpal Roy
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Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,Ecology ,Physiology ,Genetics ,Cell Biology - Abstract
C. tropicalis is a major concern for candidiasis in India and C. auris has emerged as a resistant yeast causing difficult-to-treat infections. Currently, amphotericin B (AMB) and 5-flucytosine (5-FC) are the main therapeutics for systemic fungal infections; however, the nephrotoxicity of AMB and resistance to 5-FC is a serious concern.
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- 2023
41. Efficacy of generic forms of itraconazole capsule in treating subjects with chronic pulmonary aspergillosis
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Inderpaul Singh Sehgal, Keshavamurthy Vinay, Sahajal Dhooria, Valliappan Muthu, Kuruswamy Thurai Prasad, Ashutosh Nath Aggarwal, Arunaloke Chakrabarti, Shivaprakash M. Rudramurthy, Hansraj Choudhary, and Ritesh Agarwal
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Infectious Diseases ,Dermatology ,General Medicine - Published
- 2023
42. LDBio Aspergillus immunochromatographic test lateral flow assay for IgG/IgM antibody detection in chronic pulmonary aspergillosis: Single-centre evaluation and meta-analysis
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Shreya Singh, Hansraj Choudhary, Sourav Agnihotri, Inderpaul Singh Sehgal, Ritesh Agarwal, Harsimran Kaur, Anup Ghosh, Arunaloke Chakrabarti, and Shivaprakash M. Rudramurthy
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Microbiology (medical) ,Aspergillus ,Immunoglobulin M ,Immunoglobulin G ,Chronic Disease ,Humans ,Persistent Infection ,Pulmonary Aspergillosis ,Sensitivity and Specificity ,Antibodies, Fungal - Abstract
Chronic pulmonary aspergillosis (CPA) is an infection of the lung usually caused by Aspergillus fumigatus in patients with pre-existing pulmonary diseases. Its diagnosis hinges on demonstrating IgG antibodies against A. fumigatus. Herein, we evaluated the performance of a newly introduced point of care test (POCT) kit, the LDBio Aspergillus IgG/IgM lateral flow assay (LFA) in India with the standard ImmunoCAP kit for diagnosing CPA.A total of 60 serum samples (30 CPA cases and 30 controls) were evaluated by the Aspergillus immunochromatographic test (ICT) IgG/IgM LFA. Fluorescent-enzyme immunoassay was used to determine specific A. fumigatus-IgG concentrations (positive27 mgA/L). Further, a systematic review and meta-analysis of studies (up to August 26, 2021) reporting the performance of LDBio ICT for the diagnosis of CPA was performed.A sensitivity of 86.7%, specificity of 90%, negative predictive value of 87.1%, positive predictive value of 89.7%, negative likelihood ratio of 0.15, positive likelihood ratio of 8.67, and was observed for the LDBio IC. There was good agreement between LDBio ICT and ImmunoCAP (88.3%) with a Cohen's Kappa score of 0.77. Our systematic review identified four studies and the pooled sensitivity of 90%, specificity of 91%, area under the curve of 0.94 and diagnostic odds ratio of 57.2, for CPA diagnosis by LDBio ICT.Aspergillus LDBio ICT assay exhibits good sensitivity and can be used to screen CPA cases.
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- 2022
43. Deciphering the Neurosensory Olfactory Pathway and Associated Neo-Immunometabolic Vulnerabilities Implicated in COVID-Associated Mucormycosis (CAM) and COVID-19 in a Diabetes Backdrop—A Novel Perspective
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Maryada Sharma, Hari Pankaj Vanam, Naresh K. Panda, Sourabha K. Patro, Rhythm Arora, Sanjay K. Bhadada, Shivaprakash M. Rudramurthy, Mini P. Singh, and Purushotham Reddy Koppula
- Abstract
Recent Mucorales-mediated outbreaks of infections and an association of fungal infection with COVID-19 cases, as observed for COVID-19-associated mucormycosis (CAM), have posed new challenges for the management of patients in critical care units. Diabetes and hyperglycemia are integrally linked to the severity of COVID-19, and uncontrolled diabetes mellitus and COVID-19 have recently been (independently or in combination) associated with the emergence of aggressive mucormycosis due to attendant defects in innate immune recognition pathways. Therefore, the identification of novel global cellular stressors upregulated during diabetes to understand the contribution of diabetes-associated metabolic vulnerabilities can help build a Metabolic-Stress-Associated Interactome (MSAI). This interactome can help reshape the metabolic inflammation (meta-inflammation) underlying the clinical manifestations of COVID-19 to facilitate the rational design of effective therapies for COVID-19 and CAM. Accordingly, an important area of research in COVID-19 therapeutics is engaged with identifying diabetes-associated pan-cellular stressors to understand their role in immune deregulation during COVID-19 and CAM, including investigating the distant trans-neuro-vascular–endocrine axis’s role in coordinating cellular-stress recognition, transmission, compensation, and decompensation during inter-organ regulation of metabolic homeostasis in diabetes. We reviewed clinico-pathological and laboratory data to propose potential diabetes-linked novel neo-vulnerabilities that can reshape the olfactory mucosal immune landscape during airway infections such as COVID-19 and CAM.
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- 2022
44. Intergenic spacer (IGS-1) region sequence-based identification, genotypic analysis, and antifungal susceptibility of clinical Trichosporon species
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Abhila Parashar, Vijaylatha Rastogi, Hariprasath Prakash, Abhishek Pandey, and Shivaprakash M. Rudramurthy
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Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,Immunology and Microbiology (miscellaneous) ,Immunology ,Immunology and Allergy ,Microbiology - Published
- 2023
45. Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis
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Valliappan Muthu, Sahajal Dhooria, Inderpaul Singh Sehgal, Kuruswamy Thurai Prasad, Shivaprakash M. Rudramurthy, Ashutosh N. Aggarwal, Arunaloke Chakrabarti, and Ritesh Agarwal
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Pulmonary and Respiratory Medicine ,Biochemistry (medical) ,Pharmacology (medical) - Published
- 2023
46. Anticryptococcal activity and mechanistic studies of short amphipathic peptides
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Shams Aaghaz, Komal Sharma, Indresh K. Maurya, Shivaprakash M. Rudramurthy, Shreya Singh, Vinod Kumar, Kulbhushan Tikoo, and Rahul Jain
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Drug Discovery ,Pharmaceutical Science - Abstract
Cryptococcus neoformans, an opportunistic fungal pathogen, causes cryptococcosis in immunocompromised persons. A series of modified L-histidines-containing peptides are synthesized that exhibit promising activity against C. neoformans. Analog 11d [L-His(2-adamantyl)-L-Trp-L-His(2-phenyl)-OMe] produced potency with an IC
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- 2023
47. Serum iron indices in COVID‐19‐associated mucormycosis: A case–control study
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Arunaloke Chakrabarti, Naresh K. Panda, Navneet Sharma, Ritesh Agarwal, Kuruswamy Thurai Prasad, Valliappan Muthu, Inderpaul Singh Sehgal, Ashok Kumar Pannu, Shivaprakash M Rudramurthy, Prashant Sharma, Reena Das, and Mohan Kumar H
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Male ,medicine.medical_specialty ,Iron ,Dermatology ,Gastroenterology ,Hypoxemia ,Internal medicine ,Diabetes mellitus ,invasive mould ,Diabetes Mellitus ,medicine ,Humans ,Mucormycosis ,aspergillosis ,transferrin ,chemistry.chemical_classification ,biology ,medicine.diagnostic_test ,Transferrin saturation ,business.industry ,ferritin ,Case-control study ,SARS‐CoV ,COVID-19 ,Original Articles ,General Medicine ,Middle Aged ,medicine.disease ,Ferritin ,Infectious Diseases ,chemistry ,Transferrin ,Case-Control Studies ,Ferritins ,Mucorales ,biology.protein ,Serum iron ,Original Article ,Female ,medicine.symptom ,business - Abstract
Background Whether dysregulated iron metabolism is associated with COVID‐19‐associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID‐19 subjects with and without mucormycosis. Methods We conducted a case–control study enrolling COVID‐19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron‐binding capacity [TIBC], unsaturated iron‐binding capacity and percentage transferrin saturation) between CAM cases and COVID‐19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. Results We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino‐orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID‐19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 μg/dl, p = .03) and TIBC (166.6 vs. 201.6 μg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95–0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21–22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non‐survivors. Conclusions The CAM is associated with lower TIBC levels than COVID‐19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.
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- 2021
48. Identification of distinct immunophenotypes in chronic pulmonary aspergillosis using cluster analysis
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Inderpaul S. Sehgal, Sahajal Dhooria, Valliappan Muthu, Shivaprakash M. Rudramurthy, Kuruswamy T. Prasad, Arunaloke Chakrabarti, Ashutosh N. Aggarwal, and Ritesh Agarwal
- Subjects
Infectious Diseases ,Dermatology ,General Medicine - Abstract
Whether chronic pulmonary aspergillosis (CPA) has different immunophenotypes remains unknown.To identify different CPA immunophenotypes using cluster analysis.We used a subject-centred multivariate clustering approach without prior assumptions to identify CPA phenotypes. We retrospectively included the data of treatment-naïve subjects with CPA and excluded subjects with asthma and allergic bronchopulmonary aspergillosis (ABPA). We performed a scalable two-step cluster analysis using the log-likelihood distance measures to identify CPA phenotypes based on the blood immunological profile (total IgE, eosinophil count and Aspergillus-specific IgE and IgG).We included 351 CPA subjects and found two clusters. Cluster 2 (n = 118) had significantly higher serum total IgE, peripheral blood eosinophil count, and serum A. fumigatus-specific IgE and IgG than cluster 1 (n = 233). Cluster 2 subjects had a lower FEV1:FVC ratio on spirometry and were more likely to have a fungal ball (88 [74.6%] vs. 145 (62.2%), p = .023) on the CT thorax than cluster 1. After treatment discontinuation, cluster 2 had a longer median (interquartile range) time to relapse than cluster 1 (11.5 [7.3-27.4] vs. 4 [1.1-8.9] months, p = .005).We identified two distinct CPA phenotypes, type-2 dominant and non-type-2, with different clinical and radiological findings and treatment outcomes. Future studies should confirm our findings and investigate different treatment strategies based on CPA phenotypes.
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- 2022
49. Comparison of three sample types for performing LDBio Aspergillus immunochromatographic technology lateral flow assay for IgG/IgM antibody detection in chronic aspergillosis
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Inderpaul Singh Sehgal, Sahajal Dhooria, Kathirvel Soundappan, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, and Ritesh Agarwal
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Microbiology (medical) ,Infectious Diseases ,General Medicine - Published
- 2023
50. Multicenter Epidemiologic Study of Coronavirus Disease–Associated Mucormycosis, India
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Manoj Shevkani, Rungmei S. K. Marak, Tanu Singhal, Arunaloke Chakrabarti, Pratik Savaj, Deepak Thangaraju, Nandini Sethuraman, Atul Patel, Surabhi Madan, Ritesh Agarwal, Jayanthi Savio, Shivaprakash M Rudramurthy, Ayesha Sunavala, Neha Gupta, Prakash Shastri, Karuna Tadepalli, Valliappan Muthu, Immaculata Xess, and Ratna Sharma
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Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Letter ,Epidemiology ,Antifungal drug ,India ,Infectious and parasitic diseases ,RC109-216 ,Disease ,law.invention ,respiratory infections ,law ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Mucormycosis ,Pandemics ,Retrospective Studies ,SARS ,SARS-CoV-2 ,business.industry ,Mortality rate ,COVID-19 ,Retrospective cohort study ,medicine.disease ,Intensive care unit ,Infectious Diseases ,coronavirus disease ,Medicine ,business ,severe acute respiratory syndrome coronavirus 2 - Abstract
During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.
- Published
- 2021
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