Publications by authors named "Varnica Khetrapal"

Although is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with transposon and RNA sequencing approaches, we identified the purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by during acute replication and changing carbohydrate availability during the course of wound infection.

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Despite dramatic advances in genomics, connecting genotypes to phenotypes is still challenging. Sexual genetics combined with linkage analysis is a powerful solution to this problem but generally unavailable in bacteria. We build upon a strong negative selection system to invent mass allelic exchange (MAE), which enables hybridization of arbitrary (including pathogenic) strains of .

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Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host, raising the possibility that changes in individual commensal bacteria themselves over time may affect their propensity to elicit inflammatory disease.

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The impacts of individual commensal microbes on immunity and disease can differ dramatically depending on the surrounding microbial context; however, the specific bacterial combinations that dictate divergent immunological outcomes remain largely undefined. Here, we characterize an immunostimulatory Allobaculum species from an inflammatory bowel disease patient that exacerbates colitis in gnotobiotic mice. Allobaculum inversely associates with the taxonomically divergent immunostimulatory species Akkermansia muciniphila in human-microbiota-associated mice and human cohorts.

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is the most well-studied bacterium and a common colonizer of the lower mammalian gastrointestinal tract. We report here the complete genome sequence of the original isolate, strain NCTC86, which was described by Theodor Escherich, for whom the genus is named.

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Studies of Uropathogenic Escherichia coli (UPEC) pathogenesis have relied heavily on genetic manipulation to understand virulence factors. We applied a recently reported positive-negative selection system to create a series of unmarked, scarless FimH mutants that show identical phenotypes to previously reported marked FimH mutants; these are now improved versions useful for definitive assignment of phenotypes to FimH mutations. We also increased the efficiency of this system by designing new primer sites, which should further improve the efficiency and convenience of using negative selection in UTI89, other UPEC, and other Enterobacteriaceae.

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Creation of defined genetic mutations is a powerful method for dissecting mechanisms of bacterial disease; however, many genetic tools are only developed for laboratory strains. We have designed a modular and general negative selection strategy based on inducible toxins that provides high selection stringency in clinical Escherichia coli and Salmonella isolates. No strain- or species-specific optimization is needed, yet this system achieves better selection stringency than all previously reported negative selection systems usable in unmodified E.

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