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BACKGROUND: Environmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays. METHODOLOGY: We collected drinking and surface water samples from urban, peri-urban and rural areas in 4 regions of Nepal. We performed a double agar overlay with S. Typhi to assess the presence of bacteriophages. We isolated and tested phages against multiple strains to assess their host range. We performed whole genome sequencing of isolated phages, and generated phylogenies using conserved genes. FINDINGS: S. Typhi-specific bacteriophages were detected in 54.9% (198/361) of river and 6.3% (1/16) drinking water samples from the Kathmandu Valley and Kavrepalanchok. Water samples collected within or downstream of population-dense areas were more likely to be positive (72.6%, 193/266) than those collected upstream from population centers (5.3%, 5/95) (p=0.005). In urban Biratnagar and rural Dolakha, where typhoid incidence is low, only 6.7% (1/15, Biratnagar) and 0% (0/16, Dolakha) river water samples contained phages. All S. Typhi phages were unable to infect other Salmonella and non-Salmonella strains, nor a Vi-knockout S. Typhi strain. Representative strains from S. Typhi lineages were variably susceptible to the isolated phages. Phylogenetic analysis showed that S. Typhi phages belonged to the class Caudoviricetes and clustered in three distinct groups. CONCLUSIONS: S. Typhi bacteriophages were highly abundant in surface waters of typhoid-endemic communities but rarely detected in low typhoid burden communities. Bacteriophages recovered were specific for S. Typhi and required Vi polysaccharide for infection. Screening small volumes of water with simple, low-cost (~$2) plaque assays enables detection of S. Typhi phages and should be further evaluated as a scalable tool for typhoid environmental surveillance.

Background: The emergence and persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) infections is a significant global health problem. The carrier state of typhoid makes it prudent to conduct routine surveillance for both acute cases and carriers especially those caused by MDR S. Typhi. We report on the prevalence of MDR S. Typhi, resistance phenotypes and antimicrobial resistance genes detected in symptomatic and asymptomatic children living in informal settlements in Nairobi, Kenya. Methods: 215 archived presumed S. Typhi isolates from stool samples provided by children ≤ 16 years collected from 2013 to 2018 were revived in May, 2022 and confirmed using culture and antisera serotyping. The Kirby Bauer disc diffusion technique was used to test the S. Typhi against 14 antibiotics. The MDR S. Typhi (resistant to ampicillin, chloramphenicol and sulfamethoxazole trimethoprim) which in addition were also resistant to either a cephalosporin or a fluoroquinolone were analyzed for Beta lactams and quinolone resistance genes using polymerase chain reaction. Results: A total of 215 isolates were confirmed to be positively S. Typhi; of these, 105 (49%) and 110 (51%) were from symptomatic and asymptomatic children respectively. On average, S. Typhi resistance from asymptomatic and symptomatic children against 1st line drugs was observed at; 77% &70%, ampicillin; 60% & 64%, sulfamethoxazole-trimethoprim, and 45% & 54%, chloramphenicol respectively. Multi drug resistance was observed in 90 (42%) of the isolates, of these, 44 (49%) were isolated from symptomatic and 46 (51%) from asymptomatic children. Fifteen resistance phenotypes (p) were observed with, ampicillin/chloramphenicol/sulfamethoxazole-trimethoprim/nalidixic acid (amp/chl/sxt/na) as the most common among the symptomatic 43/90 (48%) and asymptomatic 55/90 (61%) children. The blaTEM−D, AMR genes were detected in 37/44 (84%) S. Typhi isolates, out of this 18 (49%) were from symptomatic while 19 (51%) were from asymptomatic children respectively. Conclusion: The carriage of MDR S. Typhi among the asymptomatic children is concerning as they can act as potential transmitters of the typhoid disease to unsuspecting children. These study findings highlight the need for continued surveillance of antimicrobial resistance and mass immunization of children living in these urban informal areas. [ABSTRACT FROM AUTHOR]

Salmonella Typhi (S. Typhi) is an important pathogen causing typhoid fever worldwide. The emergence of antibiotic resistance, including that of blaTEM genes encoding to TEM -lactamases has been observed. This study aimed to investigate the dynamics of blaTEM genes in S. Typhi by analyzing the phylogeny and flanking region patterns and phylogenetic associating them with metadata (year, country) and genomic data (genotypes, antibiotic resistance genes (ARGs), plasmids). Genomic sequences of publicly available S. Typhi harboring blaTEM (n = 6079), spanning from 1983 to 2023, were downloaded and analyzed using CSIPhylogeny for phylogeny, Flankophile for identifying genetic contexts around blaTEM genes and GenoTyphi for determining genotypes, ARGs and plasmid replicons. We found that blaTEM-positive isolates occurred most commonly in specific location, especially in Asia and Africa and clustered among a limited number of genotypes. Flankophile identified 740 isolates (12.2%) with distinct flanking region patterns, which were categorized into 13 patterns. Notably, 7 patterns showed a predominantly phylogenetic association with genotypes. Additionally, these 7 patterns exhibited relation to the country, ARGs and plasmid replicons. Further examination of the flanking region patterns provided association with mobile genetic elements (MGEs). Taken together, this study suggests that blaTEM has been acquired by S. Typhi isolates a limited number of times and subsequently spread clonally with specific genotypes. [ABSTRACT FROM AUTHOR]

The antibacterial activity of ZnO nanorods (NRs) has been tested for its ability to inhibit the cells of pathogenic bacteria such as Staphylococcus aureus and Salmonella sp. This study aims to increase the antibacterial activity through modification of Mg2+ doped ZnO morphology under sol-gel-hydrothermal synthesis conditions at pH 10. The mechanism of biosynthetic reactions was using enzymatic grooves of the cell phyllosphere isolate of gambir (Uncaria) leaves as a reducing compound and capping agent. The X-ray diffraction (XRD) analysis showed that ZnO and Mg doped ZnO products were wurtzite structures based on intensities 2θ = 31.78°, 34.43°, 36.27° correlated to hkl (100), (002), (101), respectively (ICSD standard −157724). Mg doped ZnO has the same intensity as the control and no impurity intensity was obtained. Scanning electron microscope (SEM) analysis showed nanospheric morphological patterns, while nanorods have a more dominant size distribution in the range of 125–175 nm. Infrared (FT-IR) analysis at wave numbers 401–584 cm−1 showed a Zn-O stretch. Furthermore, powder ultraviolet (UV-DRS) analysis indicated optical properties based on the uptake on blue-shift regions with λmax ≤ 400 nm and had a change in the bandgap (Eg) of 3.37 eV after conversion using Tauc-plot. The results also showed that the greater the concentration of Mg+2 ions, the smaller the bandgap will be, i.e., of 3.13, eV, 3.10, eV, 3.11 eV, and 3.12 eV for 0, 1, 2, and 3%, respectively. On the antibacterial activity against bacteria Gram (+) Staphylococcus aureus and Gram (–) Salmonella typhi., the largest inhibitory zone was found on Gram (–) bacteria at 24 mm. [ABSTRACT FROM AUTHOR]

Background: Rising antimicrobial resistance (AMR) in Salmonella Typhi restricts typhoid treatment options, heightening concerns for pan-oral drug-resistant outbreaks. However, lack of long-term temporal surveillance data on AMR in countries with high burden like Bangladesh is scarce. Our study explores the AMR trends of Salmonella Typhi isolates from Bangladesh, drawing comparisons with antibiotic consumption to optimize antibiotic stewardship strategies for the country. Methodology/Principal findings: The typhoid fever surveillance from 1999 to 2022 included two pediatric hospitals and three private clinics in Dhaka, Bangladesh. Blood cultures were performed at treating physicians' discretion; cases were confirmed by microbiological serological, and biochemical tests. Antibiotic susceptibility was determined following CLSI guidelines. National antibiotic consumption data for cotrimoxazole, ciprofloxacin, and azithromycin was obtained from IQVIA-MIDAS database for comparison. Over the 24 years of surveillance, we recorded 12,435 culture-confirmed typhoid cases and observed declining resistance to first-line drugs (amoxicillin, chloramphenicol, and cotrimoxazole); multidrug resistance (MDR) decreased from 38% in 1999 to 17% in 2022. Cotrimoxazole consumption dropped from 0.8 to 0.1 Daily defined doses (DDD)/1000/day (1999–2020). Ciprofloxacin non-susceptibility persisted at >90% with unchanged consumption (1.1–1.3 DDD/1000/day, 2002–2020). Low ceftriaxone resistance (<1%) was observed, with slightly rising MIC (0.03 to 0.12 mg/L, 1999–2019). Azithromycin consumption increased (0.1 to 3.8 DDD/1000/day, 1999–2020), but resistance remained ≤4%. Conclusion: Our study highlights declining MDR amongst Salmonella Typhi in Bangladesh; first-line antimicrobials could be reintroduced as empirical treatment options for typhoid fever if MDR rates further drops below 5%. The analysis also provides baseline data for monitoring the impact of future interventions like typhoid conjugate vaccines on typhoid burden and associated AMR. Author summary: Our study addresses the pressing issue of antimicrobial resistance (AMR) in Salmonella Typhi, which severely limits treatment options for typhoid fever. Globally, it also raises concerns for a potential pan-oral drug-resistant outbreak. We conducted typhoid fever surveillance, spanning 24 years (1999–2022) across two pediatric hospitals and three private clinics in Dhaka, the capital city of Bangladesh. Our aim was to understand how the AMR landscape of Salmonella Typhi has changed over the years and its correlation with antibiotic consumption. Our findings reveal a notable decline in resistance to first-line drugs including cotrimoxazole, whose decreasing consumption showed a statistically significant correlation with reduced resistance. Ciprofloxacin non-susceptibility persisted at >90%. Ceftriaxone resistance remained low, but there was an upward trend in its minimum inhibitory concentration (MIC). Azithromycin resistance is emerging and currently at <4% but is expected to increase due to the observed 38-fold rise in azithromycin consumption. Taken together, our results establish a baseline to assess the impact of interventions like typhoid conjugate vaccines on typhoid and associated AMR in Bangladesh. Our work also suggests that decreasing resistance to the first line of drugs in Salmonella Typhi may allow for the re-introduction of first line of antimicrobials as empirical treatment options for typhoid fever. [ABSTRACT FROM AUTHOR]

Typhoid fever, caused by Salmonella enterica serovar Typhi, results in over 1.2 million cases and 29 thousand deaths annually from sub-Saharan Africa. Combating this disease requires various intervention approaches, such as typhoid conjugate vaccines and improving water, sanitation, and hygiene. Enhancing the effectiveness of these strategies necessitates a deeper understanding of the variation of the typhoid fever across the target region. Although the magnitude and variation of typhoid fever at the country level have been studied globally, sub-national variation remains underexplored. To address this gap, we collected data from 229 published reports on typhoid fever occurrences in sub-Saharan Africa between January 2000 and December 2020. The dataset includes information on the year and geographical location of observation, diagnostic tests used, and the type of studies in which typhoid fever was reported. By analyzing this dataset, we can gain insights into the sub-national heterogeneity of typhoid fever's burden in the region. This knowledge will be instrumental in designing more effective intervention strategies to combat the disease. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhi is a rod-shaped, Gram-negative, anaerobic bacterium. Every year, millions of people die due to typhoid fever, while the rest suffer from chronic disease. The cause of chronic disease is the formation of biofilms by typhoid bacteria. Biofilms provide resistance to various environmental stressors and anti-microbial agents. These biofilms are difficult to remove by commonly available antimicrobial agents because of their high tolerance to conventional methods of eradication and increasing antibiotic resistance. Therefore, alternative agents, such as medicinal plants, that can inhibit or eradicate biofilm attachment, maturation and dispersion need to be evaluated effectively as potential anti-biofilm agents. This review evaluates the role of plant oil extracts in inhibiting biofilm formation by Salmonella Typhi. This review demonstrates that plant essential oils have a great future in developing antimicrobial therapeutic drugs against microbial and biofilm-forming infections. [ABSTRACT FROM AUTHOR]

Foodborne pathogens may cause foodborne illness, which is among the major health problems worldwide. Since the therapeutic options for the treatment of the disease are becoming limited as a result of antibacterial resistance, there is an increasing interest to search for new alternatives of antibacterial. Bioactive essential oils from Curcuma sp become potential sources of novel antibacterial substances. The antibacterial activity of Curcuma heyneana essential oil (CHEO) was evaluated against Escherichia coli, Salmonella typhi, Shigella sonnei, and Bacillus cereus. The principal constituents of CHEO are ar-turmerone, β-turmerone, α-zingiberene, α-terpinolene, 1,8-cineole, and camphor. CHEO exhibited the strongest antibacterial activity against E. coli with a MIC of 3.9 µg/mL, which is comparable to that of tetracycline. The combination of CHEO (0.97 µg/mL) and tetracycline (0.48 µg/mL) produced a synergistic effect with a FICI of 0.37. Time-kill assay confirmed that CHEO enhanced the activity of tetracycline. The mixture disrupted membrane permeability of E. coli and induced cell death. CHEO at MIC of 3.9 and 6.8 µg/mL significantly reduced the formation of biofilm in E. coli. The findings suggest that CHEO has the potential to be an alternative source of antibacterial agents against foodborne pathogens, particularly E. coli. [ABSTRACT FROM AUTHOR]

Research Based Learning (RBL) is a learning method that uses contextual learning, authentic learning, problem solving, cooperative learning, hands on and minds on learning and inquiry learning. The STEM approach in learning is expected to provide meaning to students through the systematic integration of research-based knowledge, concepts and skills. STEM design begin with the identification of social problems. The social issue of typhoid fever cases caused by Salmonella enterica Typhi bacteria with a high mortality rate in the world is a public health problem. The existence of Pheretima javanica which is abundant in the environment can be utilized by conducting antibacterial activity testing and analysis of bioactive compounds by students on the form of the extract. This research is a development research carried out with the aim of developing a product and also a qualitative descriptive research which serves to provide an overview of the object. The steps in carrying out these tests were identified as part of learning that hone creative thinking skills. The results of the class experimental research showed that the N-Gain score was 0.8, which is in the high category. These results show that the application of developing problem-based learning tools with a STEM approach is effective. Learning outcomes contribute to the effort to find alternative drugs that are effective and do not cause resistance. In addition, students also produce scientific articles as learning products. This paper has implications for STEM integrated research-based learning. [ABSTRACT FROM AUTHOR]

Environmental surveillance for Salmonella Typhi may provide information on the community-level dynamics of typhoid fever in resource poor regions experiencing high disease burden. Many knowledge gaps concerning the feasibility of ES remain, especially in areas lacking formal sewage systems. We implemented protocols for S. Typhi ES, including site selection and catchment population estimation, sample concentration and testing using qPCR for S. Typhi specific gene targets. Between May 2021 and May 2022, we collected grab samples and Moore swabs from 43 sites in Blantyre, Malawi. Catchment characteristics, water quality, and human faecal contamination (qPCR for Bacteroides HF183) were also recorded. Their association with S. Typhi detection was investigated using a logistic mixed-effects regression analysis. Prevalence of S. Typhi in ES samples was 2.1% (1.1–4.0%) and 3.9% (1.9–7.9%) for grab and Moore swab samples, respectively. HF183 was associated S. Typhi positivity, with a unit increase in log genome copies/microlitre increasing the odds of detection of S. Typhi by 1.56 (95% CI: 1.29–1.89) and 1.33 (1.10–1.61) in Moore swabs and grab samples, respectively. The location and timing of S. Typhi detection through ES was not associated with the incidence of typhoid fever reported in associated catchment populations. During this period of relatively low typhoid fever incidence, wastewater surveillance continued to detect S. Typhi in human sewage and wastewater suggesting that ES using natural river systems can be a sensitive indicator of transmission. Author summary: Typhoid fever is a major public health concern throughout many low- and middle-income countries, resulting in significant morbidity and mortality. In recent years, two typhoid-conjugate vaccines have been pre-qualified, with the World Health Organization recommending their targeted use in high incidence, endemic regions. However, quality assured information on the spatio-temporal distribution of typhoid fever is lacking, and scale-up of typhoid vaccination is progressing slowly. Environmental surveillance for Salmonella Typhi in sewage and wastewater may be a cost-effective and scalable approach to identify high-burden regions, thereby motivating vaccine introduction. However, many knowledge gaps regarding the use of environmental surveillance for Salmonella Typhi remain, particularly where human wastewater is unmanaged and its disposal reliant on informal drainage channels and natural river systems. Therefore, we conducted a study in Malawi, Blantyre to ascertain the feasibility of environmental surveillance throughout an urban, natural freshwater river system. We measured S. Typhi prevalence in wastewater contaminated rivers and ditches serving a mixed land use environment with diverse population densities. Whilst detection rates of S. Typhi were relatively low, and no obvious spatial pattern of distribution was observed, this study demonstrates that the presence of S. Typhi throughout the year. It suggests that wastewater testing for S. Typhi may offer a sensitive surveillance tool that complements clinical case reporting and may help identify areas to be prioritized for vaccination rollout. [ABSTRACT FROM AUTHOR]

Despite decades of intense research, our understanding of the correlates of protection against Salmonella Typhi (S. Typhi) infection and disease remains incomplete. T follicular helper cells (TFH), an important link between cellular and humoral immunity, play an important role in the development and production of high affinity antibodies. While traditional TFH cells reside in germinal centers, circulating TFH (cTFH) (a memory subset of TFH) are present in blood. We used specimens from a typhoid controlled human infection model whereby participants were immunized with Ty21a live attenuated S. Typhi vaccine and then challenged with virulent S. Typhi. Some participants developed typhoid disease (TD) and some did not (NoTD), which allowed us to assess the association of cTFH subsets in the development and prevention of typhoid disease. Of note, the frequencies of cTFH were higher in NoTD than in TD participants, particularly 7 days after challenge. Furthermore, the frequencies of cTFH2 and cTFH17, but not cTFH1 subsets were higher in NoTD than TD participants. However, we observed that ex-vivo expression of activation and homing markers were higher in TD than in NoTD participants, particularly after challenge. Moreover, cTFH subsets produced higher levels of S. Typhi-specific responses (cytokines/chemokines) in both the immunization and challenge phases. Interestingly, unsupervised analysis revealed unique clusters with distinct signatures for each cTFH subset that may play a role in either the development or prevention of typhoid disease. Importantly, we observed associations between frequencies of defined cTFH subsets and anti-S. Typhi antibodies. Taken together, our results suggest that circulating TFH2 and TFH17 subsets might play an important role in the development or prevention of typhoid disease. The contribution of these clusters was found to be distinct in the immunization and/or challenge phases. These results have important implications for vaccines aimed at inducing longlived protective T cell and antibody responses. [ABSTRACT FROM AUTHOR]

As the effectiveness of current treatments against the development of antimicrobial resistance is declining, new strategies are required. A great source of novel secondary metabolites with therapeutics effects are the endophytic bacteria present in medicinal plants. In this study, Klebsiella aerogenes (an endophytic bacteria belonging to the Enterobacteriaceae family) was isolated from Kalanchoe blossfeldiana (a medicinal plant". The bacterial secondary metabolites were identified using GC-MS techniques. Furthermore, the antibacterial potentials were investigated against multi-drug resistance (MDR) Salmonella typhi and Staphylococcus aureus. The GC-MS chromatogram of K. aerogenes secondary metabolites extract displayed total of 36 compounds. Ethyl acetate extracts of K. aerogenes, showed mean zone of growth inhibition of 15.00 ± 1.00 against S. typhi and 7.00 ± 1.00mm against S. aureus, respectively. The extract demonstrated significant antibacterial effectiveness against S. typhi and moderate antibacterial efficacy against S. aureus, with minimum inhibitory concentration (MIC) values ranging from 0.089 to 0.39 mg/mL. The time-kill kinetics profile of the ethyl acetate extract against S. typhi revealed a decrease in the number of viable cells during the initial 5, 6, and 24 hours. Conversely, there was a sudden increase in viable cells up to 6 hours for S. aureus. The identified secondary metabolite with high percentage than others, benzeneethanamine exhibited favorable interactions (−7.2 kcal/mol) with the penicillin-binding protein (PBP2a) of S. aureus and (−7.5 kcal/mol) osmoporin (OmpC) of S. typhi, indicating its potential as a candidate for drug development against these MDR bacteria. This study reported for the first time, bacterial endophytes associated with K. blossfeldiana with antibacterial activities. [ABSTRACT FROM AUTHOR]

A series of novel quinoline-isoxazole hybrids 6a–o has been synthesized via multistep synthetic approach involving hetero Diels-alder reaction strategy. The target compounds were obtained in good yield, using low-cost readily available starting materials using simple reaction conditions. The newly synthesized compounds were confirmed using 1H NMR,13C NMR, and Mass spectroscopic analysis techniques. Further, compounds 6a–o were subjected to in vitro antimicrobial screening against various bacterial and fungal strains, such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhi, Aspergillus niger, and Candida albicans. Among these, compounds 6i, 6j, and 6 l were found most active having equally potent compared to standard drug Ampicillin and Gentamycin. Moreover, in silico studies of 6a–o with E. coli DNA gyrase through molecular docking and MD simulations showed excellent binding properties of these derivatives with protein site. [ABSTRACT FROM AUTHOR]

Controlled human infection model (CHIM) studies, which involve deliberate exposure of healthy human volunteers to an infectious agent, are recognised as important tools to advance vaccine development. These studies not only facilitate estimates of vaccine efficacy, but also offer an experimental approach to study disease pathogenesis and profile vaccine immunogenicity in a controlled environment, allowing correlation with clinical outcomes. Consequently, the data from CHIMs can be used to identify immunological correlates of protection (CoP), which can help accelerate vaccine development. In the case of invasive Salmonella infections, vaccination offers a potential instrument to prevent disease. Invasive Salmonella disease, caused by the enteric fever pathogens Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi A, B and C, and nontyphoidal Salmonella (iNTS), remains a significant cause of mortality and morbidity in low- and middle-income countries, resulting in over 200,000 deaths and the loss of 15 million DALYs annually. CHIM studies have contributed to the understanding of S. Typhi infection and provided invaluable insight into the development of vaccines and CoP following vaccination against S. Typhi. However, CoP are less well understood for S. Paratyphi A and iNTS. This brief review focuses on the contribution of vaccine-CHIM trials to our understanding of the immune mechanisms associated with protection following vaccines against invasive Salmonella pathogens, particularly in relation to CoP. [ABSTRACT FROM AUTHOR]

In various Southeast Asian countries, people have long incorporated the young green seeds of Parkia speciosa, commonly known as stink beans, into their culinary traditions. These seeds can be prepared using various cooking methods, including boiling, microwaving, stir-frying, or even consuming them raw. While several studies have explored the pharmaceutical properties of raw stink beans, this study seeks to expand our knowledge of how different extraction methods can influence the release of bioactive compounds from these young stink bean seeds. Three distinct extraction methods, namely (1) microwave-assisted water extraction, (2) boiling water extraction and (3) 50 % ethanol extraction were employed in this research. The study focused on total phenolic content and antioxidant activities, with the 50 % ethanol extraction method yielding the most promising results. Moreover, only the extract obtained from the 50 % ethanol method exhibited antimicrobial activity against 4 gram-positive bacteria, including Methicillin-Resistant Staphylococcus aureus, Staphylococcus aureus, Bacillus cereus, Micrococcus luteus and 1 gram-negative bacterium, Salmonella typhi. Notably, extracts obtained from the 3 extraction methods of young stink bean seeds exhibit varying degrees of inhibition of cancer cell growth with low cell toxicity. Taken together, our findings suggest that distinct extraction methods play a key role in obtaining different sets of bioactive compounds from the young seeds of stink beans. Therefore, various cooking methods, including stir-frying, microwaving and pickling in alcohol, may offer diverse sources of bioactive compounds for promoting consumer health. [ABSTRACT FROM AUTHOR]

The emergence of extensively drug-resistant Salmonella Typhi (XDR-S. Typhi) poses a grave public health threat due to its resistance to fluoroquinolones and third-generation cephalosporins. This resistance significantly complicates treatment options, underscoring the urgent need for new therapeutic strategies. In this study, we synthesized pyrazine carboxamides (3, 5a–5d) in good yields through the Suzuki reaction. Afterward, we evaluate their antibacterial activities against XDR-S. Typhi via the agar well diffusion method; 5d has the strongest antibacterial activity with MIC 6.25 (mg/mL). Moreover, in vitro Alkaline Phosphatase inhibitor activity was also determined; 5d is the most potent compound, with an IC50 of 1.469 ± 0.02 µM. Further, in silico studies were performed to find the type of interactions between synthesized compounds and target proteins. [ABSTRACT FROM AUTHOR]

A series of 2-[(2,6-diarylpiperidin-4-yl)hydrazono]-2,3-dihydrothiazoles (25–40) were synthesized by the reaction of respective thiosemicarbazones (9–24) with phenacyl bromide in the presence of sodium acetate-acetic acid buffer and refluxing in ethanol for 12–16 h. The newly synthesized target compounds were characterized by elemental analysis, mass, FT-IR, 1H and 13C NMR spectroscopic methods. A Structure activity relationship study was carried out for the title compounds against a panel of bacterial strains viz Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Bacillus subtilis and Klebsiella pneumonia and the fungal strains Cryptococcus neoformans, Candida albicans, Rhizopus sp, Aspergillus niger and Aspergillus flavus, respectively, using ciprofloxacin and amphotericin-B as standard drugs. These studies proved that compounds 26 and 34 against Staphylococcus aureus, 35 against P. aeruginosa,38 against B. subtilis, and 27 against K. pneumonia showed maximum inhibitory potency at the lowest concentration (6.25 µg/mL), whereas 26, 34 and 35 against C. neoformans and 26 and 27 against Candida albicans showed beneficial antifungal activity at a minimum concentration (MIC) of 6.25 µg/mL. [ABSTRACT FROM AUTHOR]

A series of 1-(2-amino-2,4,5,6,7,7a-hexahydrobenzo[b]-3-yl)-3-substitued-phenylpropane-1,3-dionederivatives were synthesized using the Gewald synthesis in first step which is followed by Baker−Venkataraman rearrangement to yield title compounds. The FTIR, MS and 1H NMR results of the produced derivatives were validated. The biological potential such as antimicrobial, antioxidant and antimycobacterial activity against a particularly virulent strain of MTB (MTB H37Ra) of the synthesized compounds were examined. Antimicrobial screening outcomes showed that compound S17 turned to be the most effective antibacterial agent against Gram positive bacteria such as Staphylococcus aureus (MIC = 16.87 µM) and Bacillus subtilis (MIC = 9.45 µM) and Gram negative bacteria such as Escherichia coli (MIC = 16.87 µM) and compound S7 against Salmonella typhi (MIC = 9.74 µM) and compound S16 displayed remarkable antifungal activity toward each Candida albicans and Aspergillus niger (MIC = 15.23 µM). The standard drugs, cefadroxil (antibacterial), have MIC value against S. aureus, B. subtilis, E. coli and S. Typhi are 16.40 µM, 32.80 µM, 16.40 µM and 16.40 µM, respectively, and fluconazole (antifungal) has MIC value 20.40 µM against both the C. albicans and A.niger strain. In comparison with ascorbic acid, a standard drug (IC50 44.91 µg/mL), compound S10 demonstrated good antioxidant activity, with an IC50 value of 45.29 µg/mL, according to the results of the antioxidant screening. The results of the in vitro antituberculosis screening showed that compound S23 was found to be effective with an MIC value of 78.125 µg/mL. Molecular docking study of an enzymatic active site of "DprE1-decaprenylphosphoryl-β-D-ribose-2′-epimerase" shows a comparable binding mode to the native ligand with better docking score which contributes in understanding and development of models for ligand–protein interactions. Compound S23 showed better docking score of − 8.516 as compared to the Isoniazid with the docking score of − 6.315 which in future will create the fundamental structural framework for MTB inhibition. [ABSTRACT FROM AUTHOR]

For millennia, people have successfully treated a wide range of illnesses, including bacterial infections, with different plant parts or extracts. "MDR strain" typically refers to a "multi-drug resistant strain" of a bacteria. In the context of infectious diseases, a multi-drug resistant strain refers to a strain of the pathogen that has acquired resistance to multiple drugs that are commonly used to treat infections caused by that specific pathogen. MDR strains can present significant challenges in healthcare settings as they limit the effectiveness of standard treatments and may require more aggressive or specialized approaches to manage the infection. The discdiffusion method was used in this investigation to test the antimicrobial properties of Petroleum ether, acetone, ethanol, methanol, and aqueous extracts of Ficus auriculata leaves against four bacterial strains namely Salmonella enteric serovar typhi, Salmonella enteric ser Paratyphi (MDR strain) Pseudomonas aeruginosa and Escherichia coli. The findings showed that all of the investigated organisms (zone of inhibition of 0.5 ± 0.15 & 18 ± 1.7 mm) were significantly inhibited by the petroleum ether, ethanol, and methanol extracts, with the exception of Salmonella typhi (an 18 mm inhibitory zone). The restricted area (=5) indicated moderate activity in the aqueous extracts. It's crucial to remember that antimicrobial activity analysis of plant extracts is just one step in the process of identifying potential natural antimicrobial agents. Further studies, including the identification and isolation of specific bioactive compounds, toxicology assessments, and clinical trials, are required before any plant extract can be considered for use as a drug development. [ABSTRACT FROM AUTHOR]

Bacteriocins are antimicrobial peptides produced by bacteria to prevent the growth of pathogens. Combining bacteriocins with metal nanoparticles, like silver nanoparticles (AgNPs), has developed into a viable strategy to get over bacteriocin limitations. In this study, bacteriocin BacZY05 was extracted from Bacillus subtilis ZY05 and purified using various techniques. The resulting purified bacteriocin was then combined with silver nanoparticles to form bacteriocin silver nanoconjugates (BacZY05-AgNPs). The physicochemical properties of the BacZY05-AgNPs were characterized using various analytical techniques. The mean diameter of the synthesized AgNPs was approximately 20–60 nm with an oval or spherical shape. The antimicrobial activity of the BacZY05-AgNPs was evaluated against several indicator strains by their zone of inhibition (ZOI), using the agar well diffusion method. Compared to bacteriocin (ZOI- 13 to 20 mm) and AgNPs (ZOI- 10–22 mm) alone, the antibacterial activity data demonstrated a 1.3-1.5-fold increase in the activity of bacteriocin-nanoconjugates (ZOI- 22 to 26 mm). For Staphylococcus aureus MTCC3103 and Klebsiella pneumoniae MTCC109, BacZY05-capped AgNPs exhibited the lowest minimum inhibitory concentration (MIC), measuring 10.93 µg/mL. For Salmonella typhi NCIM2501, the MIC was 28.75 µg/mL. The highest MIC value was 57.5 µg/mL for Escherichia coli DH5α and Vibrio cholerae MTCC3909. With BacZY05-capped AgNPs, the lowest minimum bactericidal concentration (MBC) of 28.75 µg/mL was observed for Staphylococcus aureus MTCC31003. In the cases of Salmonella typhi NCIM2501 and Klebsiella pneumoniae MTCC109 concentration was 57.5 µg/mL. Vibrio cholerae MTCC3909 and Escherichia coli DH5α had the highest MBC values at 115 µg/mL. [ABSTRACT FROM AUTHOR]

Objective: The leaves of Alstonia boonei and aerial parts of Ipomoea cairica are used for treatment of microbial infections among other ailments in African traditional medicine. The aim of this study was to investigate the antimicrobial phytochemicals in A. boonei leaves and Ipomoea cairica aerial parts to validate their traditional use in Ugandan herbal medicine. Methods: The plant materials were separately extracted using a dichloromethane/methanol (1:1) solvent system and subjected to repeated chromatographic separation to isolate pure compounds. The chemical structures of the isolated compounds were determined through 1H NMR, 13C NMR and 2D NMR (COSY, HSQC and HMBC). The antibacterial activity of the extracts and pure compounds were assessed using the agar well diffusion method. Results: Chromatographic fractionation of the extracts yielded trans -fagaramide and a pentacyclic lupane-type triterpenoid, lupeol, from A. boonei, and friedelin from I. cairica. Trans-fagaramide was identified for the first time in the Alstonia genus while friedelin was identified for the first time in I. cairica. The isolated compounds demonstrated antibacterial activity, with trans -fagaramide showing a minimum inhibitory concentration (MIC) of 125 μg/mL against Pseudomonas aeruginosa and 250 μg/mL against Staphylococcus aureus, Salmonella typhi and Escherichia coli. Friedelin exhibited a MIC of 125 μg/mL against Escherichia coli and 250 μg/mL against Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhi. Conclusion: The antibacterial activities observed in this study support the traditional use of A. boonei and I. cairica by indigenous communities in Uganda for treating microbial infections. [ABSTRACT FROM AUTHOR]

Background and Objectives: In the undertaken study, proteomics alterations of blood-borne XDR S. Typhi isolated from Pakistan were investigated using mass spectrometry. Materials and Methods: MDR and XDR S. Typhi total protein lysates were fractionated, digested, and processed for nanoflow LC-LTQ-Orbitrap MS analysis. Results: Among the 1267 identified proteins, 37 were differentially regulated, of which 28 were up-regulated, and 9 were down-regulated in XDR S. Typhi as compared to MDR S. Typhi. Based on the functional annotation, proteins found up-regulated are involved mainly in metabolic pathways (ManA, FadB, DacC, GpmA, AphA, PfkB, TalA, FbaB, OtsA, 16504242), the biosynthesis of secondary metabolites (ManA, FadB, GlpB, GpmA, PfkB, TalA, FbaB, OtsA), microbial metabolism in diverse environments (FadB, GpmA, PfkB, NfnB, TalA, FbaB), and ABC transporters (PstS, YbeJ, MglB, RbsB, ArtJ). Proteins found down-regulated are involved mainly in carbon metabolism (FadB, GpmA, PfkB, FalA, FbaB) and the biosynthesis of amino acids (GpmA, PfkB, TalA, FbaB). Most of the identified differential proteins were predicted to be antigenic, and matched with resistome data. Conclusions: A total of 28 proteins were up-regulated, and 9 were down-regulated in XDR S. Typhi. Further characterization of the identified proteins will help in understanding the molecular signaling involved in the emergence of XDR S. Typhi. [ABSTRACT FROM AUTHOR]

Abstract Background The emergence and persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) infections is a significant global health problem. The carrier state of typhoid makes it prudent to conduct routine surveillance for both acute cases and carriers especially those caused by MDR S. Typhi. We report on the prevalence of MDR S. Typhi, resistance phenotypes and antimicrobial resistance genes detected in symptomatic and asymptomatic children living in informal settlements in Nairobi, Kenya. Methods 215 archived presumed S. Typhi isolates from stool samples provided by children ≤ 16 years collected from 2013 to 2018 were revived in May, 2022 and confirmed using culture and antisera serotyping. The Kirby Bauer disc diffusion technique was used to test the S. Typhi against 14 antibiotics. The MDR S. Typhi (resistant to ampicillin, chloramphenicol and sulfamethoxazole trimethoprim) which in addition were also resistant to either a cephalosporin or a fluoroquinolone were analyzed for Beta lactams and quinolone resistance genes using polymerase chain reaction. Results A total of 215 isolates were confirmed to be positively S. Typhi; of these, 105 (49%) and 110 (51%) were from symptomatic and asymptomatic children respectively. On average, S. Typhi resistance from asymptomatic and symptomatic children against 1st line drugs was observed at; 77% &70%, ampicillin; 60% & 64%, sulfamethoxazole-trimethoprim, and 45% & 54%, chloramphenicol respectively. Multi drug resistance was observed in 90 (42%) of the isolates, of these, 44 (49%) were isolated from symptomatic and 46 (51%) from asymptomatic children. Fifteen resistance phenotypes (p) were observed with, ampicillin/chloramphenicol/sulfamethoxazole-trimethoprim/nalidixic acid (amp/chl/sxt/na) as the most common among the symptomatic 43/90 (48%) and asymptomatic 55/90 (61%) children. The bla TEM−D, AMR genes were detected in 37/44 (84%) S. Typhi isolates, out of this 18 (49%) were from symptomatic while 19 (51%) were from asymptomatic children respectively. Conclusion The carriage of MDR S. Typhi among the asymptomatic children is concerning as they can act as potential transmitters of the typhoid disease to unsuspecting children. These study findings highlight the need for continued surveillance of antimicrobial resistance and mass immunization of children living in these urban informal areas.

Abstract Salmonella Typhi (S. Typhi) is an important pathogen causing typhoid fever worldwide. The emergence of antibiotic resistance, including that of bla TEM genes encoding to TEM $$\:\beta\:$$ -lactamases has been observed. This study aimed to investigate the dynamics of bla TEM genes in S. Typhi by analyzing the phylogeny and flanking region patterns and phylogenetic associating them with metadata (year, country) and genomic data (genotypes, antibiotic resistance genes (ARGs), plasmids). Genomic sequences of publicly available S. Typhi harboring bla TEM (n = 6079), spanning from 1983 to 2023, were downloaded and analyzed using CSIPhylogeny for phylogeny, Flankophile for identifying genetic contexts around bla TEM genes and GenoTyphi for determining genotypes, ARGs and plasmid replicons. We found that bla TEM-positive isolates occurred most commonly in specific location, especially in Asia and Africa and clustered among a limited number of genotypes. Flankophile identified 740 isolates (12.2%) with distinct flanking region patterns, which were categorized into 13 patterns. Notably, 7 patterns showed a predominantly phylogenetic association with genotypes. Additionally, these 7 patterns exhibited relation to the country, ARGs and plasmid replicons. Further examination of the flanking region patterns provided association with mobile genetic elements (MGEs). Taken together, this study suggests that bla TEM has been acquired by S. Typhi isolates a limited number of times and subsequently spread clonally with specific genotypes.

INTRODUCTION: Salmonella Typhi and Salmonella Paratyphi, fecal-oral transmitted bacterium, have temporally and geographically heterogeneous pathways of transmission. Previous work in Kathmandu, Nepal implicated stone waterspouts as a dominant transmission pathway after 77% of samples tested positive for Salmonella Typhi and 70% for Salmonella Paratyphi. Due to a falling water table, these spouts no longer provide drinking water, but typhoid fever persists, and the question of the diseases dominant pathway of transmission remains unanswered. METHODS: We used environmental surveillance to detect Salmonella Typhi and Salmonella Paratyphi A DNA from potential sources of transmission. We collected 370, 1L drinking water samples from a population-based random sample of households in the Kathmandu and Kavre Districts of Nepal between February and October 2019. Between November 2019 and July 2021, we collected 380, 50mL river water samples from 19 sentinel sites on a monthly interval along the rivers leading through the Kathmandu and Kavre Districts. We processed drinking water samples using a single qPCR and processed river water samples using differential centrifugation and qPCR at 0 and after 16 hours of liquid culture enrichment. A 3-cycle threshold (Ct) decrease of Salmonella Typhi or Salmonella Paratyphi, pre- and post-enrichment, was used as evidence of growth. We also performed structured observations of human-environment interactions to understand pathways of potential exposure. RESULTS: Among 370 drinking water samples, Salmonella Typhi was detected in 7 samples (1.8%) and Salmonella Paratyphi A was detected in 4 (1.0%) samples. Among 380 river water samples, Salmonella Typhi was detected in 171 (45%) and Salmonella Paratyphi A was detected in 152 (42%) samples. Samples located upstream of the Kathmandu city center were positive for Salmonella Typhi 12% of the time while samples from locations in and downstream were positive 58% and 67% of the time respectively. Individuals were observed bathing, washing clothes, and washing vegetables in the rivers. IMPLICATIONS: These results suggest that drinking water was not the dominant pathway of transmission of Salmonella Typhi and Salmonella Paratyphi A in the Kathmandu Valley in 2019. The high degree of river water contamination and its use for washing vegetables raises the possibility that river systems represent an important source of typhoid exposure in Kathmandu.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal sentinel surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortiums aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Abstract Background Understanding the source of typhoid infections and the genetic relatedness of Salmonella Typhi (S. Typhi) by cluster identification in endemic settings is critical for establishing coordinated public health responses for typhoid fever management. This study investigated the genotypic diversity, antibiotic resistance mechanisms, and clustering of 35 S.Typhi strains isolated from cases and carriers in the Mukuru Informal Settlement. Methods We studied 35 S.Typhi isolates, including 32 from cases and 3 from carriers, from study participants in the informal settlement of Mukuru, Nairobi, Kenya. Genomic DNA was extracted, and whole-genome sequencing (WGS) was performed to determine the phylogenetic relatedness of strains and detect antimicrobial resistance determinants (AMR). WGS data were analyzed using bioinformatics tools available at the Center for Genomic Epidemiology and Pathogenwatch platforms. Results Genotype 4.3.1.2 EA3 was found to be dominant at 46% (16/35), followed by 4.3.1.2 EA2 at 28% (10/35), and 4.3.1.1 EA1 at 27% (9/35). A comparison of the isolates with global strains from Pathogenwatch identified close clustering with strains from Uganda, Tanzania, Rwanda, and India. Three isolates (9%) distributed in each cluster were isolated from carriers. All genotype 4.3.1.2 EA3 isolates were genotypically multidrug-resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Single mutations in the quinolone resistance-determining region were identified in the gyrA (S83Y) and gyrB (S464F) genes. All isolates associated with multidrug resistance showed the presence of the IncQ1 plasmid with the following genes: blaTEM-1B, catA1, sul1, sul2, and dfrA7. Conclusion The close phylogenetic relatedness between antimicrobial-resistant case isolates and carriage isolates indicates that typhoid carriage is a possible source of infection in the community. Comparative analysis with global isolates revealed that the Kenyan isolates share common lineages with strains from neighboring East African countries and India, suggesting regional dissemination of specific MDR clones. AMR was a major feature of the isolates. Surveillance and testing for antimicrobial susceptibility should inform options for the management of cases.

The study presents the data on organization of laboratory testing of clinical and environmental samples within the framework of establishing the etiology of the acute intestinal infections outbreak, performed by the specialists of the joint SAET of the Rospotrebnadzor in Dolisie (Republic of the Congo) in the period of 07–24 July, 2023.Materials and methods. In order to identify the causative agents of cholera and other acute intestinal infections of bacterial and viral nature, 177 clinical and environmental samples were tested, as well as cultures on solid nutrient media and bacterial suspensions. A total of 1023 tests were carried out by polymerase chain reaction (PCR) and 305 – using bacteriological method.Results and discussion. The causative agent of cholera has not been detected in any of the samples tested. Using the PCR method, markers of acute intestinal diseases agents (Salmonella spp., Shigella spp., Campylobacter spp., Rotavirus A) have been identified in 23 clinical samples and 1 sample of bacterial suspension. No DNA/RNA of pathogens has been detected in environmental samples. During culture studies, Salmonella enterica serovar Typhi have been isolated from 8 clinical samples, and their antibiotic sensitivity has been determined. Applying whole-genome nanopore sequencing, using the MinIon platform (Oxford Nanopore Technologies, UK), nucleotide sequences of 4 S. Typhi isolates have been investigated and deposited in the international database NCBI GenBank (No. CP141260, CP141193, CP141194, CP141195). Additionally, the analysis of initially sterile samples (blood, peritoneal fluid, intraoperational samples) from the patients of General and Reference hospitals of Dolisie has resulted in the identification of 5 cultures of non-fermenting bacteria, and their antibiotic sensitivity has been determined.

The speciation of Salmonella occurred by acquisition of genomic islands from other bacterial species and continued to diverge into subspecies and serovars with diferent range of host. S. enterica serovar Typhimurium (STM) is a generalist pathogen infecting hosts that include birds, mice, and humans, whilst S. enterica serovar Typhi (STY) is a restricted-host pathogen, infecting only humans. Despite their ranges of hosts, STM and STY possess 97-98% identity. Gain of genes by horizontal transference and loss of genes by mutations, are believed essential for differentiation of Salmonella. Salmonella pathogenicity island 3 (SPI-3) is an example combining these two processes. SPI-3 encodes misL and marT, among other genes. In STM, misL is required for gut colonization. Furthermore, protein MarT, positively regulates expression of misL by binding to misL-promoter. On the other hand, in SPI-3 of STY, marT and misL are pseudogenes. Interestingly, the gene t3766 (gene involved in resistance to H2O2) is present only in STY and is negatively regulated when marTSTM is heterologously expressed in STY. Based on the view that MarT might regulate genes implicated in virulence, this work searched for new genes regulated by MarT. In silico searches for possible MarT target genes were performed, and 4 genes were selected for further analysis as they contained at least 2 copies of the consensus MarT-binding sequence in their promoters. Mutating marT in STM or heterologously expressing marTSTM in STY confirmed that MarT negatively regulates ORF STY1408 or STM14_2003, its homologue in STM. STY1408 encodes for a putative protein with homology to methyl accepting chemotaxis proteins, which participate in chemotaxis and motility. Therefore, STY1408 was named mrmI (MarT-regulated motility gene I). Motility assays confirmed that the product of mrmI modulates motility. In addition, in vitro infection of cells with STM and STY mutants in mrmI reduces association with cells at 1, 3 and 24 h post-infection. Oral infection of mice showed that a mrmI null mutant was defective in producing systemic disease. Therefore, we conclude that MarT regulated mrmI, is involved in virulence of Salmonella. While pseudogenization of marT might modulate the fitness of narrow host range STY. [ABSTRACT FROM AUTHOR]

TiO2 nanoparticles (TiO2NPs) were prepared using the Carchorus hirsutus plant leaf extract and investigated for biomedical applications. The synthesized TiO2NPs were characterized by UV-visible, FTIR, XRD, SEM, EDS, and TEM methods and tested for haemolytic activity. The anticancer activity was investigated using MCF7 and HeLa cell lines. The antimicrobial activity was tested against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella typhi and Candida albicans. [ABSTRACT FROM AUTHOR]

Background In Santiago, Chile, where typhoid had been hyperendemic (1977–1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring during 2017–2019. Methods Culture-confirmed cases were classified as autochthonous (domestically acquired) versus travel/immigration related. Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers. Whole genome sequences of acute cases and their epidemiologically linked chronic carrier isolates were compared. Results Five of 16 autochthonous typhoid cases (31.3%) were linked to 4 chronic carriers in case households; 2 cases (onsets 23 months apart) were linked to the same carrier. Carriers were women aged 69–79 years with gallbladder dysfunction and Typhi fecal excretion; 3 had highly elevated serum anti-Vi titers. Genomic analyses revealed close identity (≤11 core genome single-nucleotide polymorphism [SNP] differences) between case and epidemiologically linked carrier isolates; all were genotypes prevalent in 1980s Santiago. A cluster of 4 additional autochthonous cases unlinked to a carrier was identified based on genomic identity (0-1 SNPs). Travel/immigration isolate genotypes were typical for the countries of travel/immigration. Conclusions Although autochthonous typhoid cases in Santiago are currently rare, 5 of 16 such cases (31.3%) were linked to elderly chronic carriers identified among household contacts of cases. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to assess the antimicrobial activities of various polar and nonpolar solvent extracts derived from the leaves of Viola odorata. The disc diffusion method was employed to test the antimicrobial susceptibility against a diverse range of pathogenic microorganisms, including Escherichia coli, Erwinia carotovora, Klebsiella pneumoniae, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and the fungus Candida albicans. The results indicated that isobutanol and ethyl acetate fractions exhibited significantly higher antimicrobial activity compared to petroleum ether, crude, chloroform and aqueous fractions. Among the tested bacteria, E. carotovora was the most susceptible bacterium to all the extracts of V. odorata, whereas S. typhi demonstrated the highest resistance. The isobutanol extract inhibited the proliferation of E. carotovora by 62 % at a concentration of 2 mg disc-1, while the ethyl acetate extract achieved 53% inhibition under the same conditions. Additionally, our findings revealed that the overall antimicrobial activity of V. odorata leaves was consistently effective against both Gram-positive and Gram-negative bacterial strains. [ABSTRACT FROM AUTHOR]

Litsea mekongensis Lecomte is a native species that originated in Vietnam and Laos. To date, the volatile components and antibacterial activity of the essential oils derived from L. mekongensis leaves have not yet been reported. This study aims to investigate the chemical composition and antibacterial activity of L. mekongensis leaf essential oil. The chemical constituents were analyzed by gas chromatography-mass spectroscopy (GC-MS), and the antibacterial activity was evaluated using the agar well diffusion method. The GC-MS analysis showed that fifty-four volatile components were detected, of which sesquiterpene hydrocarbons accounted for almost 65% of the total, while the proportion of monoterpene hydrocarbons was 19.84%. Germacrene D (16.17%), γ-elemene (7.82%), β-phellandrene (6.76%), α-pinene (6.62%), and δ-cadinene (5.68%) were identified as major components. The essential oil exhibited strong antibacterial activity against Salmonella typhi, Staphylococcus aureus, and Escherichia coli. S. aureus was the most sensitive species, but no inhibitory activity against Pseudomonas aeruginosa was recorded. These findings revealed information on the chemical constituents of the essential oil prepared from L. mekongensis and its potential antibacterial activity against several pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Food‐related stresses such as heating and freezing may influence the biofilm formation ability of bacteria. This study aimed to investigate the main and interactive effects of food‐related stresses on the biofilm formation potential of Salmonella strains isolated from meat. Salmonella enteritidis, Salmonella typhi, and Salmonella typhimurium were subjected to osmotic, acid, heat, cold, and freezing stresses. The colorimetric microtiter plate method was used to measure the biofilm formation ability as a response to the stresses. Among the main effects, freezing time had the most significant effect on the biofilm formation responses of three Salmonella serovars. Freezing reduced the biofilm formation ability of Salmonella typhimurium and Salmonella enteritidis but increased that of Salmonella typhi (p < 0.05). Among the interaction effects, the most significant effect on the biofilm formation response of Salmonella typhi was the interaction between pH and heat, which had a negative effect on the biofilm formation response. In contrast, the interaction between osmotic pressure and cold stresses was the most significant interactive effect on the biofilm formation responses of Salmonella enteritidis and Salmonella typhimurium, which had an increasing effect. This study concluded that the food‐related stresses could change the biofilm formation capacity of Salmonella serotypes, and each serotype might show different biofilm formation abilities in response to different stresses. [ABSTRACT FROM AUTHOR]

Bacterial contamination in fruits and vegetables cultivated in urban and peri-urban areas constitutes a serious public health risk. This paper investigates bacterial contamination in irrigation water of the Nairobi-Machakos counties interface, Kenya. Sixty-six irrigation water samples were tested for total coliforms, Escherichia coli, Shigella spp. Pseudomonas aeruginosa, Enterococcus faecalis, Vibrio cholerae, Salmonella typhi, BOD, COD, and pH. Results show a high load of bacterial pathogens in all samples except for Salmonella typhi, which tested negative. Based on Kenya's standards and WHO guidelines, the irrigation water samples are unfit for fruit and vegetable irrigation. Urgent and effective measures are required, including regular monitoring, sensitisation, and enforcement of phytosanitary and regulatory measures. [ABSTRACT FROM AUTHOR]

In a one-pot reaction involving 3-(2-aminothiazol-5-yl)-2H-chromen-2-one/5-(naphthalen-1-yl)thiazol-2-amines 5-6 with various substituted aldehydes and mercaptoacetic acid, we obtained the corresponding 2-(4-substituted-phenyl)-3-[5-(2-oxo-2H-chromen-3-yl)thiazol-2-yl] thiazolidin-4-ones 8(a-h) and 2-(4-substituted-phenyl)-3-[5-(naphthalen-1-yl)thiazol-2-yl] thiazolidin-4-ones 9(a-h). The antimicrobial activity of all compounds was evaluated against Pseudomonas aeruginosa (MTCC-424), Salmonella typhi (MTCC-531), Staphylococcus aureus (MTCC-737), and Candida albican (MTCC-227). Molecular docking further supported the findings, which showed that the compounds 8d and 9d had excellent antibacterial action against all tested pathogens. [ABSTRACT FROM AUTHOR]

Background: Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar's hospital population. Methodology: A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. S. typhi infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods. Drug sensitivity testing on cultures was conducted as per the CLSI guidelines. Chi-square tests were used to analyze the clinical and epidemiologic characteristics of 5735 samples stratified by S. typhi infection status, and risk factors were assessed by applying logistic regression models to estimate odds ratios (ORs). Results: The number of confirmed typhoid fever cases in this hospital-based study population was 691 (/5735, 12.0%), more prevalent in males (447/3235 13.8%) and children (0–11 years) (429/2747, 15.6%). Compared to children, the risk of S. typhi infection was lower in adolescence (adjusted OR = 0.52; 95% CI: 0.42–0.66), adulthood (19–59 years; aOR = 0.30; 95% CI: 0.25–0.38), and older adulthood (aOR = 0.08; 95% CI: 0.04–0.18) (p < 0.001). Compared to males, the risk of S. typhi infection was lower in females (aOR = 0.67; 95% CI = 0.56–0.80; p = 0.002). Living in a rural residence (compared to urban) was associated with a higher risk of infection (aOR = 1.38; 95% CI: 1.16–1.63; p = 0.001), while access to a groundwater source (compared to municipal water supply) led to a lower risk (aOR = 0.56; 95% CI: 0.43–0.73; p = 0.002). Vaccination demonstrated a robust protective effect (aOR = 0.069; 95% CI = 0.04–0.11, p = 0.002). For those with typhoid infections, clinical biomarker analysis revealed the presence of leucopenia (65/691, 9.4%), thrombocytopenia (130/691, 18.8%), and elevated alanine aminotransferase (ALT) (402/691, 58.2%) and C-reactive protein (CRP) (690/691, 99.9%) levels. Worryingly, among the positive S. typhi isolates, there was a high prevalence of drug resistance (653/691), including multidrug-resistant (MDR 82/691, 11.9%) and extensively drug-resistant types (XDR, 571/691, 82.6%). Conclusions: This study highlights the importance of age, sex, locality, water source, and vaccination status in shaping the epidemiological landscape of S. typhi in the Peshawar district. It implies that expanding vaccination coverage to the broader population of Khyber Pakhtunkhwa province, particularly in the district of Peshawar, would be beneficial. [ABSTRACT FROM AUTHOR]

Salmonella Typhi is a human-restricted pathogen that is transmitted by the faecal–oral route and causative organism of typhoid fever. Using health facility data from 2016 to 2020, this study focuses on modelling the spatial variation in typhoid risk in Ndirande township in Blantyre. To pursue this objective, we developed a marked inhomogeneous Poisson process model that allows us to incorporate both individual-level and environmental risk factors. The results from our analysis indicate that typhoid cases are spatially clustered, with the incidence decreasing by 54% for a unit increase in the water, sanitation, and hygiene (WASH) score. Typhoid intensity was also higher in children aged below 18 years than in adults. However, our results did not show evidence of a strong temporal variation in typhoid incidence. We also discuss the inferential benefits of using point pattern models to characterise the spatial variation in typhoid risk and outline possible extensions of the proposed modelling framework. [ABSTRACT FROM AUTHOR]

Invasive non-typhoidal Salmonella (iNTS) disease is an under-recognized high-burden disease causing major health and socioeconomic issues in sub-Saharan Africa (sSA), predominantly among immune-naïve infants and young children, including those with recognized comorbidities such as HIV infection. iNTS disease is primarily caused by Salmonella enterica serovar Typhimurium sequence type (ST) 313 and 'African-restricted clades' of Salmonella Enteritidis ST11 that have emerged across the African continent as a series of epidemics associated with acquisition of new antimicrobial resistance. Due to genotypes with a high prevalence of antimicrobial resistance and scarcity of therapeutic options, these NTS serovars are designated by the World Health Organization as a priority pathogen for research and development of interventions, including vaccines, to address and reduce NTS associated bacteremia and meningitis in sSA. Novel and traditional vaccine technologies are being applied to develop vaccines against iNTS disease, and the results of the first clinical trials in the infant target population should become available in the near future. The "Vaccine Value Profile" (VVP) addresses information related predominantly to invasive disease caused by Salmonella Enteritidis and Salmonella Typhimurium prevalent in sSA. Information is included on stand-alone iNTS disease candidate vaccines and candidate vaccines targeting iNTS disease combined with another invasive serotype, Salmonella Typhi, that is also common across sSA. Out of scope for the first version of this VVP is a wider discussion on either diarrheagenic NTS disease (dNTS) also associated with Salmonella Enteritidis and Salmonella Typhimurium or the development of a multivalent Salmonella vaccines targeting key serovars for use globally. This VVP for vaccines to prevent iNTS disease is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic, and societal value of pipeline vaccines and vaccine-like products. Future versions of this VVP will be updated to reflect ongoing activities such as vaccine development strategies and a "Full Vaccine Value Assessment" that will inform the value proposition of an iNTS disease vaccine. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the World Health Organization African Region. All contributors have extensive expertise on various elements of the iNTS disease VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information. [ABSTRACT FROM AUTHOR]

Background: Understanding the source of typhoid infections and the genetic relatedness of Salmonella Typhi (S. Typhi) by cluster identification in endemic settings is critical for establishing coordinated public health responses for typhoid fever management. This study investigated the genotypic diversity, antibiotic resistance mechanisms, and clustering of 35 S.Typhi strains isolated from cases and carriers in the Mukuru Informal Settlement. Methods: We studied 35 S.Typhi isolates, including 32 from cases and 3 from carriers, from study participants in the informal settlement of Mukuru, Nairobi, Kenya. Genomic DNA was extracted, and whole-genome sequencing (WGS) was performed to determine the phylogenetic relatedness of strains and detect antimicrobial resistance determinants (AMR). WGS data were analyzed using bioinformatics tools available at the Center for Genomic Epidemiology and Pathogenwatch platforms. Results: Genotype 4.3.1.2 EA3 was found to be dominant at 46% (16/35), followed by 4.3.1.2 EA2 at 28% (10/35), and 4.3.1.1 EA1 at 27% (9/35). A comparison of the isolates with global strains from Pathogenwatch identified close clustering with strains from Uganda, Tanzania, Rwanda, and India. Three isolates (9%) distributed in each cluster were isolated from carriers. All genotype 4.3.1.2 EA3 isolates were genotypically multidrug-resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Single mutations in the quinolone resistance-determining region were identified in the gyrA (S83Y) and gyrB (S464F) genes. All isolates associated with multidrug resistance showed the presence of the IncQ1 plasmid with the following genes: blaTEM-1B, catA1, sul1, sul2, and dfrA7. Conclusion: The close phylogenetic relatedness between antimicrobial-resistant case isolates and carriage isolates indicates that typhoid carriage is a possible source of infection in the community. Comparative analysis with global isolates revealed that the Kenyan isolates share common lineages with strains from neighboring East African countries and India, suggesting regional dissemination of specific MDR clones. AMR was a major feature of the isolates. Surveillance and testing for antimicrobial susceptibility should inform options for the management of cases. [ABSTRACT FROM AUTHOR]

Patients with cancer have weakened immune systems, making them more vulnerable to infections. This study was carried out to determine the bacterial origins of enteric disorders in cancer patients and noncancer patients at the Oncology Department of Laquintinie Hospital in Douala. A cross‐sectional study was conducted from October 2021 to March 2023. Stool samples from 307 cancer patients with enteric disorders and 200 noncancer patients with enteric disorders were examined to diagnose the presence of bacteria using various techniques. Among all participants in this study, 62.13% were female and 37.87% were male. The average age of the participants was 46.38 ± 15.81 years, with a minimum age of 10 years and a maximum age of 84 years. The average age of participants was significantly higher (p < 0.000) in cancer patients (49.54 ± 14.65 years) compared to noncancer patients (41.53 ± 16.33 years). Proteus mirabilis, Proteus vulgaris, Salmonella typhi, Enterobacter cloacae, Klebsiella pneumoniae, Yersinia intemedia, and Klebsiella oxytoca were more frequently isolated in cancer patients than in noncancer patients, with the respective percentages of 56.25% versus 43.75%, 50.00% versus 50.00%, 61.66% versus 38.34%, 66.66% versus 33.34%, 72.22% versus 27.78%, 80.00 versus 20.00%, and 100% versus 0.00%. Most isolates were sensitive to imipenem (IMP), gentamicin (GEN), and amikacin (AMK). Proteus vulgaris, the most prevalent isolate, showed significantly high resistance (with p < 0.05) in cancer patients compared to noncancer patients at amoxicillin/clavuranic acid (AMC) (89.13% versus 41.30%), ceftriaxone (CTR) (63.04% versus 39.13%), ciprofloxacin (CIP) (65.22% versus 34.18%), and tetracycline (TET) (93.48% versus 63.04%). Multidrug resistance was observed in cancer patients compared to noncancer patients for Klebsiella pneumoniae (85.00% versus 60.00%), Salmonella typhi (84.62% versus 60.00%), and Klebsiella oxytoca (86.49% versus 43.48%). The increase in the number of Gram‐negative infections among cancer patients, as shown in the present study, highlights the need for broad‐spectrum therapy and effective planning of control programs to reduce bacterial diseases among cancer patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the chemical composition and antimicrobial activity of laurel leaf extracts obtained using different methods and solvents. Extraction was performed using the Soxhlet, ultrasound-assisted, and orbital shaker methods with water, ethanol, methanol, ethyl acetate, acetone, hexane and chloroform. The chemical compositions of the extracts were analyzed with a gas chromatograph coupled to a mass spectrometer and a flame ionization detector (GC-MS-FID). The GC-MS-FID results were compared to data of the Wiley and National Institute of Standards and Technology (NIST) libraries to identify the chemical composition of the analytes. The antimicrobial activities of the extracts against Staphylococcus aureus NCTC10788, Bacillus cereus NCTC7464, Salmonella typhi NCTC11994, Listeria monocytogenes ATCC11994 and Escherichia coli NCTC2001 were determined with in-house disc diffusion testing. The highest efficiency was achieved using the Soxhlet method and methanol (49.11%). Among the solvents tested, hexane, and among the methods used, ultrasound-assisted extraction exhibited the lowest efficiency (P<0.05). The extracts showed a stronger inhibitory effect on Grampositive bacteria (P<0.05). The highest level of antimicrobial activity was achieved against S. aureus with the use of the stock solution concentrations of the extracts obtained with the combined use of the ultrasound-assisted method and the solvents ethanol, ethyl acetate, acetone and hexane. The bacteria most resistant to almost all concentrations of the laurel leaf extracts were S. typhi, E. coli and L. monocytogenes. The method and solvent for extraction should be chosen carefully, depending on the targeted molecules and desired activity. [ABSTRACT FROM AUTHOR]

Objective: Pakistan bears most of the burden of drug-resistant typhoid, challenging its healthcare systems with substantial cost. This study’s purpose is to investigate resistance in community-acquired salmonella typhi to guide its evidence-based empiric treatment. Material & Methods: This study used retrospective data from the microbiology laboratory, Khyber Teaching Hospital, Peshawar (September 2022-March 2023). Data of routine diagnostic samples for typhoid was retrieved from the database. Kirby– Bauer disk diffusion method was employed to determine the sensitivity of S. Typhi against a panel of 21 selected antibiotic discs (not exclusively for each isolate). Results: Among 1742 suspected patients, 239 (13.92%) were positive for S. Typhi with 212/238 (89.1%), 227/233 (97.4%), and 196/239 (82.0%) isolates resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, respectively. High resistance (88.0% to ciprofloxacin) was detected against fluoroquinolones. Third-generation cephalosporins also showed poor activity with 144/158 (91.1%) and 120/136 (88.2%) resistance towards ceftriaxone and cefixime, respectively, except for cefoperazone/sulbactam (2/123, 1.6%). Among 157 tested isolates, 3 (1.9%), 9 (5.7%), and 123 (78.3%) were labeled as non-resistant, MDR, and XDR strains, respectively. XDRs were less resistant to azithromycin (1/114), piperacillin/tazobactam (1/123), carbapenems (0/123), and tigecycline (0/123). Conclusion: XDR S. Typhi was observed as the dominant strain in Peshawar regions for which azithromycin is still the drug of choice. With emerging resistance, azithromycin safety should be ensured through antibiotic stewardship principles. An interesting finding was the enhanced activity of cefoperazone/sulbactam, suggesting future studies. Alternative options are expensive antibiotics which can be used as a last resort. [ABSTRACT FROM AUTHOR]

Objectives 1. To determine the etiological profile of suspected cases of bacteremia 2. To establish the antibiotic susceptibility pattern of bacterial isolates Materials and Methods: The retrospective study was carried out from January 2022 to December 2022 at Islamabad International Hospital. A total of 639 blood culture isolates were processed manually onto blood agar, chocolate agar, MacConkey’s agar, and bile-esculin agar and were identified on their morphological appearance using gram staining. Isolates were further identified at the species level using the Analytic Profile Index (API). Antibiotic susceptibility testing was performed using the Disk Diffusion method as per Clinical and Laboratory Standards Institute guidelines (M-100 Version 2021) Results: Amongst 639 blood culture isolates, only 66 (10.32%) were culture-positive. Prevalent gram-negative bacilli included Salmonella typhi (n= 19) and Escherichia coli (n= 8) whilst Enterococcus (n=4), and Staphylococcus aureus (n=4) were the predominant gram-positive cocci. Salmonella typhi and S. aureus showed 100% resistance to ciprofloxacin whilst enterococcus displayed 75% resistance. Overall, all strains (n=6) of K. pneumoniae and 63% of E. coli showed resistance to over 4 antibiotics. Conclusion: Gram-negative bacteria were the main cause of BSIs, where the predominant microorganism was S. typhi. Remarkably all S. typhi isolates were completely resistant to ciprofloxacin. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the epidemiology, clinical features, and complications of extensively drugresistant Salmonella typhi (XDR S. typhi) infection in adults. Method: This cross-sectional study enrolled adults with culture-proven XDR S. typhi admitted to Hayatabad Medical Complex, Peshawar from 1st March to 10th September 2022. Their demographic characteristics, clinical features, treatment, and complications were recorded. Results: Out of 84 patients, 68 (80.9%) were male. The mean age of enrolled patients was 25.2 ± 11.3 years. The mean duration of fever at the time of admission was 13.6 ± 8.2 days, respectively. The most common symptom was loose stools (n=25, 29.8%). Most of the patients (n=69, 82.1%) had received empirical treatment before hospitalization. The majority of the patients (n=42, 50%) received meropenem and a combination of meropenem and azithromycin (n=35, 41.7%) during the study. The time to defervescence for both regimens was similar. Five patients (6%) developed complications of enteric fever. There was no mortality among the participants. Conclusions: Diarrhea was the most common associated clinical feature in XDR typhoid fever. Most of the patients received meropenem alone or in combination with azithromycin with a comparable time to defervescence. The majority of the patients recovered uneventfully and there was no mortality among the study participants. [ABSTRACT FROM AUTHOR]

Objectives: To determine the antimicrobial activity of silver nano-particles(AgNPs) with tetracycline and ampicillin against multi-drug resistance (MDR) and extensively-drug resistance (XDR) Salmonella typhi. Methods: Cross sectional non-probability purposive study was conducted from September, 2021 to May, 2022 at Microbiology department PNS Shifa, Hospital Karachi. Blood cultures of patients suspicious of typhoid fever were collected and incubated in automated Bact/Alert system. Positive cultures were identified on blood and MacConkey and processed by API-10S, confirmed by serotyping (O9 antisera) (SSI Diagnostica's Salmonella). Antibiotic resistance was done by Kirby-Bauer disk diffusion (Sigma and Rich). MDR and XDR isolates were preserved in Brain Heart Infusion in a volume of 2ml in screw capped bottles at -70°C. Antimicrobial powders (ampicillin and tetracycline (Alfa Aesar) weighed by an electrical weighing balance (OHAUS) to take 1mg of antimicrobial drug. Absorbance spectra of serial concentrations of antibiotics (UV-Vis spectrophotometer (Mole-Qule-) AgNPs (10nm) (nanocomposix) + Antibiotic in (1:1 volume ratio). Conjugation of silver nanoparticles with tetracycline and ampicillin was done by FTIR (thermos scientificThermos ScientificNicolet 50). Results: Out of 77 isolates, 54 were resistant to ceftriaxone (XDR) and 23 sensitive to ceftriaxone (MDR). All isolates were susceptible to azithromycin and meropenem. Comparison of zone of inhibitions of ampicillin and Amp-AgNPsas and tetracycline with Tet-AgNPs was done. Minimal inhibitory concentration was also done to determine antimicrobial activity. Conclusion: Significant synergistic inhibitory effects against Salmonella Typhi isolates were obtained by combination of tetracycline with silver nano-particles even at low concentration. [ABSTRACT FROM AUTHOR]

This investigation was applied to isolate and identify bacteria in three different restaurants order to predict their effects on people. Power plate method for isolation of bacteria the samples were inoculated into nutrient agar media by streak plate technique to obtain well isolated colonies. The results show the identity and the total colony forming units (CFU) for bacteria. The most frequently isolated bacteria were the bacterial species: Bacillus cereus, Clostridium botulinum, Escherichia coli, Salmonella typhi, Shigella dysenteriae, Staphylococcus aureus and Lactobacillus subtilus (11.12, 8.24, 20.11,17.32, 17.01, 10.31 and 8.27) % respectively. According to the bacteria the higher numbers of bacteria were isolated on menu and containers. [ABSTRACT FROM AUTHOR]

Marine organisms are vast sources of bioactive components, with holothorians, or sea cucumbers being one of these sources. Therefore, sea cucumber specimens were examined as a promising source of natural substances that can be used as antibacterial, antifungal, anti-inflammatory, antioxidant, antiviral, and antitumor agents. Holothuria papillifera was collected from Zaafarana, Ras Ghareb, and Altur stations and employed as a biological weapon against some pathogens. H. papillifera extracts showed high activity as antibacterial extracts against Staph. aureus and Enterococcus faecalis (Gram+ve), Escherichia coli, Salmonella typhi, and Klebsiella pneumoniae (Gram-ve). It also exhibited positive antifungal efficacy against Candida albicans and revealed moderate activity against liver cancer cells and a weak activity against breast cancer cells. Alternatively, H. papillifera crude extract has weak antiviral activity against CoxB4 and very weak antiviral efficacy against HAV (hepatitis A virus). Moreover, our results proved that H. papillifera extract had anti-inflammatory effects and exhibited antioxidant power. In conclusion, H. papillifera has broad antimicrobial activity against many pathogens, as well as antioxidant, antitumor, anti-inflammatory, among others. It is recommended to explain and characterize the composition of the bioactive compounds of H. papillifera to be included in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate antidiarrheal potential of prickly pear cladode and its hepatoprotective role in different groups of diarrhea‐induced mice. Mice received cefixime (4 mg/kg of bw) and different concentrations of aqueous cladode extract (250 mg/kg of bw, 500 mg/kg of bw and 1000 mg/kg of bw). Feces Salmonella typhi ATCC 19430 was used to assess antidiarrheal potential and hematological, biochemical parameters, and histopathological analyses were carried out for 17 days. The results showed that administration of Salmonella typhi ATCC 19430 in mice produced liver injuries with histological damage, whereas 1000 mg/kg of bw cladode extract reduced the Salmonella typhi ATCC 19430 load of feces earlier as compared to the other groups during 17 days. Hematological parameters, like red blood cells (RBCs) (6.19 ± 1.85 × 106/mm3) and hemoglobin (Hb) (10.06 ± 2.03 g/dL), of negative control group decreased, while white blood cells (WBCs) (13.46 × 106/mm3) increased from reference values. In lipid profile, low‐density lipoprotein (LDL) (9.0 ± 2.41 mg/dL), high‐density lipoprotein (HDL) (6.07 ± 2.45 mg/dL) and total cholesterol (TC) (35.22 ± 8.29 mg/dL) of negative control group decreased, while triglycerides (TG) (168.35 ± 71.75 mg/dL) increased from reference values. Alanine transferase (ALT) (60.30 ± 20.33 IU/L), alkaline phosphatase (ALP) (359.9 ± 100.05 IU/L) and aspartate transferase (AST) (168.77 ± 66.61 IU/L) of negative control group increased from reference values. Urea (27.36 ± 10.54 mmol/L) and creatinine (35.29 ± 12.15 mmol/L) of the negative control group increased. Cefixime also ameliorated injuries due to the administration of Salmonella typhi ATCC 19430. Conclusively, these findings indicated that pure aqueous extract of cladode showed more promising results regarding antidiarrheal potential. Hence, cladode might be used in food and supplement formulations as a functional ingredient. [ABSTRACT FROM AUTHOR]

Salmonella Typhi infection is showing as a negative alarm for human health due to the occurrence of life-threatening typhoid fever and the emergence of antibiotic resistance. The infection becomes chronic due to the biofilm formation of S. Typhi, which plays a significant role in antibiotic resistance. The S. Typhi can survive under various stress conditions such as antibiotic stress, host immune stress, environmental stress, and nutritional stress in the biofilm stage. Biofilm provides a protective cover to the S. Typhi and prevents the entry of antibiotics inside the bacterial cells. Thus, biofilm is the root cause of the problem. Therefore, this study explores the easy detection of S. Typhi biofilms using safranin dye with specific concentrations. We performed the biofilm growth kinetics, qualitative assessment of the biofilm formations, and safranin interactions to finalize the specific concentrations of safranin (0.5 mg/mL) to detect the S. Typhi biofilm condition. The study was validated at 0.5 mg/mL safranin concentrations with the help of RSM analysis and kinetics study of the typhoidal biofilm. The study is important because the obtained results indicated the precise detection of S. Typhi biofilm, which is useful for all phases of biofilm detection. The study provided new directions for typhoidal biofilm staining that could be an emerging methodology in the area of health sciences. [ABSTRACT FROM AUTHOR]