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Worldwide Candida albicans infections cause a huge burden in healthcare and the efficacy of traditional antifungals is diminished because of the rapid development of antifungal resistance. It is necessary to develop new antifungals or new strategies to make multidrug-resistant (MDR) C. albicans to resensitize to existing antifungal drugs. In this work, a series of 4-arm polypeptoids (FAPs) were synthesized through grafting linear ε-l-lysine or δ-ornithine-based oligopeptides to a trimeric lysine core. The most potent 4R-O7 exhibited excellent activities toward three sensitive and two MDR C. albicans strains with MIC values as low as 24-48 μg/mL (vs 375 μg/mL for ε-polylysine, ε-PL). The mechanism studies revealed that 4R-O7 penetrated the cell membrane and generated ROS to kill cells. 4R-O7 exhibited a synergistic effect (FICI < 0.5) with voriconazole (VOR) and also assisted VOR to restore its efficacy to MDR C. albicans . In addition, the combined use of 4R-O7 and VOR significantly improved the elimination efficacy of mature C. albicans biofilms and enhanced the potency in a mouse subcutaneous C. albicans infection model.

Background: Resistance to antifungal drugs for treating Candida infections remains a major concern globally despite the range of medications available. Most of these drugs target key proteins essential to the life cycle of the organism. An enzyme essential for fungal cell membrane integrity, lanosterol 14–α demethylase (CYP51), is encoded by the ERG11 gene in Candida species. This enzyme is the target of azole–based drugs. The organism has, however, devised molecular adaptations to evade the activity of these drugs. Materials and Methods: Classical methods were employed to characterize clinical isolates sampled from women and dogs of reproductive age. For fluconazole efficacy studies, CLSI guidelines on drug susceptibility testing were used. To understand the susceptibility pattern, various molecular and structural analytic approaches, including sequencing, in silico site-directed mutagenesis, and protein-ligand profiling, were applied to the ERG11 gene and CYP51 protein sequences. Several platforms, comprising Clustal Omega, Pymol plugin manager, Pymol molecular visualizer, Chimera–curated Dynameomics rotamer library, protein–ligand interaction profiler, Charmm36 force field, GROMACS, Geneious, and Mega7, were employed for this analysis. Results: The following Candida species distribution was obtained: 37.84% C. albicans, 8.12% C. glabrata, 10.81% C. krusei, 5.41% C. tropicalis, and 37.84% of other unidentified Candida species. Two codons in the nucleotide sequence of the wild-type (CTC and CCA) coding for LEU– 370 and PRO– 375, respectively, were mutated to L370S and P375H in the resistant strain. The mutation stabilized the protein at the expense of the heme moiety. We found that the susceptible isolate from dogs (Can–iso– 029/dog) is closely related to the most resistant isolate from humans. Conclusion: Taken together, our results showed new mutations in the heme-binding pocket of caCYP51 that explain the resistance to fluconazole exhibited by the Candida isolates. So far, the L370S and P375H resistance-linked mutations have not been previously reported. [ABSTRACT FROM AUTHOR]

A vaginal yeast infection called vaginal candidiasis is the most commonly seen type of Candida infections with a rate of 37%. Vaginal candidiasis affects three fourth (75%) of women in their lifetimes, and this is the most common cause of women seeking gynecological care. Vaginal candidiasis can result in serious symptoms such as discharge, itching, burning sensation, pain, rash and irritation in the vagina and vulva. Candida albicans, in particular, is the most common cause of vaginal candidiasis. Therefore, the treatment and control process of Candida species is very important in terms of health. In this study, as a first step, Microbial Chondroitin Sulfate was produced from Escherichia coli C2987 strain by using a specific microbial system and reliable biotechnological methods. After that, the efficacy of Microbial CS as an antifungal agent on C. albicans strains was tested by using the agar dilution method. As a result, it was determined that the Microbial CS was particularly effective against the yeasts C. albicans, and the minimum inhibitory concentration of Microbial CS was 0.32 g/mL. Our findings showed that Microbial CS can be used in the content of various biomedical products that can be used as an antifungal agent for Candida sp. Microbial CS can also be used to treat the disease alone or to support the treatment that increases the efficacy of antibiotics. [Med-Science 2020; 9(2.000): 433-6]

Background: It is well documented in the literature that fungal infections are common in diabetic foot ulcers (DFUs). This has led to an overuse of antifungal agents, namely fluconazole, with a consequent risk of emergence of resistance to this drug. Previous studies have shown a 3.9% prevalence of fluconazole resistance in DFU, but limited data exist regarding the change in resistance pattern over the last decade. Objectives: Our aim was to study the prevalence of resistance to fluconazole in patients with DFU and culture-proven fungal infections. Materials and Methods: We retrospectively studied 1438 patients with type 2 diabetes and nonhealing foot ulcers who had fungal cultures performed during the course of their treatment. The data were collected for all patients who presented to our foot clinic over a period of 18 months. Results: The prevalence of positive fungal culture was 17.38% (250/1438). 151/200 positive cultures belonged to Candida species. Resistance to fluconazole was observed in 9.3% (17/200). The most common organism with resistance to fluconazole was Candida auris (10/17). Conclusions: High prevalence of fluconazole resistance is a potential cause of concern, and the rational use of this drug is important in the community. The above results could have an impact on public health, as fluconazole is one of the safest and effective oral antifungal agents available. The spread of resistance could have implications for its use in other situations including systemic fungal infections.

The objective of this study was to evaluate the effect of breast feeding duration on the presence of Candida in relation to nonnutritive sucking habits. This study was conducted by multistage sampling method. In the first stage calculation of the sample size was done, while in the second stage questionnaires were distributed to obtain the children personal information including: the date of birthday, gender, type of feeding, breast feeding duration, presence the nonnutritive sucking habits (dummy sucking, thumb sucking) with the duration of the habit. In the third stage, a sample of 100 children attending private and public kindergarten in Baquba city/Iraq were identified (50 children with nonnutritive sucking habits and the other 50 were without any sucking habits). Samples had been obtained from the oral cavity of the selected children and cultured on sabauraud dextrose agar media, identification of Candida albicans was done by germ tube under the light microscope. A highly significant relation was found between the duration of breast-feeding and the presence of Candida, by which the mean rank of the presence of Candida was higher among children with breast feeding duration less than 6 months than children who got breast-feeding for more than 6 months. Although the mean rank of the candida among the study group was higher than that among the control group, the difference was statistically not significant. The mean rank of Candida was higher among children with mixed feeding than the children with breast-feeding and the difference was statistically highly significant. Type of feeding has an impact on the presence of Candida among children. Concerning the presence of Candida, children who fed with their mother's milk for 6 months or more had the lowered median. [ABSTRACT FROM AUTHOR]

Background and Purpose: Candida species are emerging as a potentially pathogenic fungus in pulmonary diseases. The synergistic growth promoting association of candida and mycobacterium tuberculosis has increased concern for studying the various candida spp. and its significance in pulmonary tuberculosis patients. This study was undertaken with the objective of discovering the study of virulence factors of Candida species isolated from pulmonary tuberculosis with diabetes mellitus. Materials and Method: A total of 110 patients with pulmonary tuberculosis diagnosed by sputum Ziehl-Neelsen staining were included in the study. Candida co-infection was confirmed using the Kahanpaa et al. criteria. Candida species were identified using gram stain morphology, germ tube formation, morphology on cornmeal agar with Tween-80, sugar fermentation tests and HiChrom Candida Agar. Results: Candida co-infection was observed in 53 (48%) of patients with pulmonary tuberculosis. Candida albicans was the most common isolate observed in 62% of the patients with co-infection, followed by C. parapsilosis (11.3%) and 5 were C. krusei (9.4%). Candida co-infection was found in 52.8% of female patients, while it was observed in only 47.1% of the male patients. Conclusion: Candida spp. isolated from pulmonary tuberculosis patients has significantly higher production of virulence factors. Candida co-infection should be routinely practiced along with extracellular hydrolytic enzymatic activity and biofilm production of NAC Spp. The identification of the gene responsible for the colonization may provide novel targets for antifungal prophylaxis. [ABSTRACT FROM AUTHOR]

Fungal infections in humans have historically received comparatively less attention than those caused by bacteria and viruses. This may, in part, stem from the relative differences in infection prevalence. However, the more widespread use of immunosuppressive therapy, invasive surgery and medical devices in modern medicine has resulted in a more frequent occurrence of human fungal infection. There are a number of fungi that can cause human disease. However, it is arguably a species of the genus Candida that are most often encountered. There are over 150 Candida species that are widely encountered in the environment and in animal hosts, however, only a small number are opportunistic pathogens of humans. Candida albicans is a polymorphic yeast-like fungus and undoubtedly the species most often recovered from human infection. As such, the virulence of C. albicans and its susceptibility to antifungal agents are often investigated. More recently, the prevalence of infections caused by non-C. albicansCandida species have increased and, amongst these, infections caused by Candida glabrata have received attention given its often-higher tolerance to frequently used antifungals exhibited by this species. The papers presented in this Special Issue have focused on aspects relating to host responses to Candida infection, the efficacy of novel therapeutic agents and also treatment regimes. The papers highlight novel findings in their respective areas, whilst also highlighting the need for further research in these key and largely under-researched areas of candidoses.

Candida species are opportunistic pathogens responsible for a variety of diseases, ranging from skin and mucosal lesions to severe systemic, life-threatening infections. Candida albicans accounts for more than 70% of all Candida infections, however, the clinical relevance of other species such as Candida parapsilosis and Candida krusei are being increasingly recognized. Biofilm-producing yeasts cells acquire an increased resistance to antifungal agents, often leading to therapeutic failure and chronic infection. Conventional methods such as crystal violet (CV) and tetrazolium (XTT) reduction assay, developed to evaluate biofilm formation in Candida species are usually time-consuming, present a high intra- and inter-assay variability of the results and are therefore hardly applicable to routine diagnostics. This study describes an in-vitro assay developed for the measurement of biofilm formation in Candida species based on the clinical Biofilm Ring Test® (cBRT). We found a significant concordance between the cBRT and both CV (k = 0.74) and XTT (k = 0.62), respectively. Nevertheless, the cBRT resulted more reliable and reproducible than CV and XTT, requiring a minimal sample manipulation and allowing a high throughput assessment, directly on viable cells. The results indicate that the cBRT may provide a suitable, cost-effective technique for routine biofilm testing in clinical microbiology. [ABSTRACT FROM AUTHOR]

Not long after birth, yeast, predominantly Candida albicans, colonizes the epithelium of oral cavity and the whole gastrointestinal tract. C. albicans lives in yeast, a non-harming form, as a commensal member of the microbial flora, but may turn into pathogen infective form under certain conditions that encourage its overgrowth. In this phase, it may damage the intestinal wall and enter the bloodstream, causing invasive candidiasis with high mortality rate. It is essential to recognize candidaemia and start the lifesaving therapy on time. Recognizing the risk factors which allow candida to overgrow is the most important step in preventing candida's overgrowth and chronic candidiasis, the previous status of invasive candidiasis. If this recognition is missed, and the overgrowth advances, a question remains how to discover and treat it and in which phase it should be done. A stool culture requires time and proves the presence of live yeast cells only. If the live yeast cells are not present in the stool, the result of the culture will be negative. In this paper, the author presents her experience of stool analysis under dark-field microscope, as a rapid, easy to carry out method for detecting the presence of live or dead yeast cells and yeast overgrowth. [ABSTRACT FROM AUTHOR]

Background: It is well documented in the literature that fungal infections are common in diabetic foot ulcers (DFUs). This has led to an overuse of antifungal agents, namely fluconazole, with a consequent risk of emergence of resistance to this drug. Previous studies have shown a 3.9% prevalence of fluconazole resistance in DFU, but limited data exist regarding the change in resistance pattern over the last decade. Objectives: Our aim was to study the prevalence of resistance to fluconazole in patients with DFU and culture-proven fungal infections. Materials and Methods: We retrospectively studied 1438 patients with type 2 diabetes and nonhealing foot ulcers who had fungal cultures performed during the course of their treatment. The data were collected for all patients who presented to our foot clinic over a period of 18 months. Results: The prevalence of positive fungal culture was 17.38% (250/1438). 151/200 positive cultures belonged to Candida species. Resistance to fluconazole was observed in 9.3% (17/200). The most common organism with resistance to fluconazole was Candida auris (10/17). Conclusions: High prevalence of fluconazole resistance is a potential cause of concern, and the rational use of this drug is important in the community. The above results could have an impact on public health, as fluconazole is one of the safest and effective oral antifungal agents available. The spread of resistance could have implications for its use in other situations including systemic fungal infections. [ABSTRACT FROM AUTHOR]

Fungal infections in humans have historically received comparatively less attention than those caused by bacteria and viruses. This may, in part, stem from the relative differences in infection prevalence. However, the more widespread use of immunosuppressive therapy, invasive surgery and medical devices in modern medicine has resulted in a more frequent occurrence of human fungal infection. There are a number of fungi that can cause human disease. However, it is arguably a species of the genus Candida that are most often encountered. There are over 150 Candida species that are widely encountered in the environment and in animal hosts, however, only a small number are opportunistic pathogens of humans. Candida albicans is a polymorphic yeast-like fungus and undoubtedly the species most often recovered from human infection. As such, the virulence of C. albicans and its susceptibility to antifungal agents are often investigated. More recently, the prevalence of infections caused by non-C. albicansCandida species have increased and, amongst these, infections caused by Candida glabrata have received attention given its often-higher tolerance to frequently used antifungals exhibited by this species. The papers presented in this Special Issue have focused on aspects relating to host responses to Candida infection, the efficacy of novel therapeutic agents and also treatment regimes. The papers highlight novel findings in their respective areas, whilst also highlighting the need for further research in these key and largely under-researched areas of candidoses. [ABSTRACT FROM AUTHOR]