Collinsella aerofaciens linked with increased ethanol production and liver inflammation contribute to the pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.

Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

Gut microbiome and non-alcoholic fatty liver disease.

The human gastrointestinal tract (GIT) contains a dynamic and diverse collection of bacteria, archaea, and fungi termed the "gut microbiome." The gut microbiome has a major impact on the host during homeostasis and disease. The connection between both the host and the microbiome is complex, although its manipulation may assist prevent or treating a multitude of morbidities. These microorganisms play a critical role in the host's energy metabolism and homeostasis. According to new research, the microbes in the gastrointestinal tract play a substantial role in host health, and alterations in its composition and function might lead to the emergence of metabolic disorders like non-alcoholic fatty liver disease (NAFLD). The resilience of the GIT microbial ecology and its tolerance to perturbation are robust but not ideal. Several factors may disrupt the GIT microbiome's homeostasis leading to dysbiosis, characterized by an imbalanced equilibrium and perturbations in gut homeostasis. Irritable bowel disease (IBD), malnutrition, and metabolic disorders, such as NAFLD, have been associated with the dysbiotic gut microbiome. Recent evidence suggests that utilizing medications, prebiotics, probiotics, and fecal microbiota transplantation (FMT) to manipulate the microbiome could be a viable method for treating NAFLD.

Region-specific genomic signatures of multidrug-resistant Helicobacter pylori isolated from East and South India.

Helicobacter pylori is a ubiquitous bacterium and contributes significantly to the burden of chronic gastritis, peptic ulcers, and gastric cancer across the world. Adaptive phenotypes and virulence factors in H. pylori are heterogeneous and dynamic. However, limited information is available about the molecular nature of antimicrobial resistance phenotypes and virulence factors of H. pylori strains circulating in India. In the present study, we analyzed the whole genome sequences of 143 H. pylori strains, of which 32 are isolated from two different regions (eastern and southern) of India. Genomic repertoires of individual strains show distinct region-specific signatures. We observed lower resistance phenotypes and genotypes in the East Indian (Kolkata) H. pylori isolates against amoxicillin and furazolidone antibiotics, whereas higher resistance phenotypes to metronidazole and clarithromycin. Also, at molecular level, a greater number of AMR genes were observed in the east Indian H. pylori isolates as compared to the southern Indian isolates. From our findings, we suggest that metronidazole and clarithromycin antibiotics should be used judicially in the eastern India. However, no horizontally acquired antimicrobial resistance gene was observed in the current H. pylori strains. The comparative genome analysis shows that the number of genes involved in virulence, disease and resistance of H. pylori isolated from two different regions of India is significantly different. Single-nucleotide polymorphisms (SNPs) based phylogenetic analysis distinguished H. pylori strains into different clades according to their geographical locations. Conditionally beneficial functions including antibiotic resistance phenotypes that are linked with faster evolution rates in the Indian isolates.

Biogenic Synthesis of Silver Nanoparticles (AgNPs) Using Aqueous Leaf Extract of Buchanania lanzan Spreng and Evaluation of Their Antifungal Activity against Phytopathogenic Fungi.

Nanoparticles show the multidisciplinary versatile utility and are gaining the prime place in various fields, such as medicine, electronics, pharmaceuticals, electrical designing, cosmetics, food industries, and agriculture, due to their small size and large surface to volume ratio. Biogenic or green synthesis methods are environmentally friendly, economically feasible, rapid, free of organic solvents, and reliable over conventional methods. Plant extracts are of incredible potential in the biosynthesis of metal nanoparticles owing to their bountiful availability, stabilizing, and reducing ability. In the present study, the aqueous leaf extract of Buchanania lanzan Spreng was mixed with 0.5 mM silver nitrate and incubated at 70°C for 1 h and synthesized a good quantity of AgNPs. The synthesized AgNPs were characterized using UV-visible spectroscopy, X-ray diffractometry (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The maximum absorption of UV-visible spectra was obtained in the range of 420-430 nm. Furthermore, SEM and TEM results inferred that the size of the particles were 23-62 nm, spherical, crystalline, uniformly distributed, and negatively charged with the zeta potential of -27.6 mV. In addition, the antifungal activities of the AgNPs were evaluated against two phytopathogenic fungi Rhizoctonia solani and Fusarium oxysporum f. sp. lycopersici in vitro using poison food techniques on PDA media. The maximum rate of mycelia inhibition was found in 150 ppm concentration of AgNPs against both phytopathogenic fungi.

Genetic and mutational analysis of virulence traits and their modulation in an environmental toxigenic Vibrio cholerae non-O1/non-O139 strain, VCE232.

Vibrio cholerae O1 and O139 isolates deploy cholera toxin (CT) and toxin-coregulated pilus (TCP) to cause the diarrhoeal disease cholera. The ctxAB and tcpA genes encoding CT and TCP are part of two acquired genetic elements, the CTX phage and Vibrio pathogenicity island-1 (VPI-1), respectively. ToxR and ToxT proteins are the key regulators of virulence genes of V. cholerae O1 and O139. V. cholerae isolates belonging to serogroups other than O1/O139, called non-O1/non-O139, are usually devoid of virulence-related elements and are non-pathogenic. Here, we have analysed the available whole genome sequence of an environmental toxigenic V. cholerae non-O1/non-O139 strain, VCE232, carrying the CTX phage and VPI-1. Extensive bioinformatics and phylogenetic analyses indicated high similarity of the VCE232 genome sequence with the genome of V. cholerae O1 strains, including organization of the VPI-1 locus, ctxAB, tcpA and toxT genes, and promoters. We established that the VCE232 strain produces an optimal amount of CT at 30 °C under AKI conditions. To investigate the role of ToxT and ToxR in the regulation of virulence factors, we constructed ΔtoxT, ΔtoxR and ΔtoxTΔtoxR deletion mutants of VCE232. Extensive genetic analyses of these mutants indicated that the toxT and toxR genes of VCE232 are crucial for CT and TCP production. However, unlike O1 isolates, the presence of either toxT or toxR gene is sufficient for optimal CT production in VCE232. In addition, the VCE232 ΔtoxR mutant showed differential regulation of the major outer membrane proteins, OmpT and OmpU. This is the first attempt to explore the regulation of expression of major virulence genes and regulators in an environmental toxigenic V. cholerae non-O1/non-O139 strain.