Biology subjects

Elsherbini, J.

Publications and source records attributed to Elsherbini, J..

4 recordsLinked to original sources

bioRxiv2025

Synergistic therapeutic effects of endolysin BNT331 and a Lactobacillus crispatus consortium in a human vagina chip model of bacterial vaginosis

Bacterial vaginosis (BV) is a vaginal infection caused by an imbalance in the vaginal microbiome characterized by a decrease in healthy bacteria dominated by Lactobacillus crispatus along with a concomitant increase in dysbiotic bacteria, such as Gardnerella. Current treatments commonly fail to fully eradicate BV, and the lack of more effective therapies is due in part to the absence of relevant human models. Here, we used a human vagina-on-a-chip (Vagina Chip) microfluidic culture device that has been previously shown to faithfully recapitulate the human vaginal microenvironment as well as the inflammatory and injurious effects of G. vaginalis to test the therapeutic efficacy of a consortium of L. crispatus alone or in combination with endolysin BNT331, which specifically targets and lyses Gardnerella. These studies revealed that when L. crispatus was added alone, it suppressed inflammation even though it failed to engraft or displace the G. vaginalis bacteria. In contrast, BNT331 effectively killed Gardnerella in dysbiotic Vagina Chip. Importantly, the combined administration of both treatments resulted in restoration of a healthier vaginal microenvironment, as indicated by higher engraftment of L. crispatus on-chip, inhibition of G. vaginalis, and a reduction in inflammation. Similar effects of this combined treatment were observed when administered to Vagina Chips infected with vaginal swab samples from BV patients. These data suggest that combination of a live biotherapeutic product composed of a L. crispatus consortium with a potent antimicrobial agent that targets G. vaginalis, such as BNT331, may offer an effective therapeutic strategy for patients with BV. One Sentence SummaryEndolysin BNT331 combined with Lactobacillus crispatus reduces bacterial load and suppresses inflammation in a human vagina chip model of bacterial vaginosis.

pathology↗

bioRxiv2025

kSanity: A k-mer based application forprecision bacterial strain detection andquantification

MotivationAccurate detection and quantification of bacterial strains in clinical samples is necessary to measure their colonization and persistence. Past methods to achieve this relied either on strain-specific qPCR assays, or shotgun metagenomic read mapping approaches. The resident microbial community is a major source of interference in both assays because it can contain conspecific strains bearing similarity to the focal strain(s). ResultsWe present kSanity, a k-mer based application for the detection and quantification of targeted bacterial strains in shotgun metagenomic data. Because kSanity uses exact string matches between the reads and reference, it is less sensitive to interference by conspecific strains. We test the performance of kSanity using a combination of in silico spike-in experiments, and in vivo observational data. Our results demonstrate that kSanity provides precise and accurate quantification of targeted bacterial strains, even when they are present at low sequence coverage in the metagenome. Availability and implementationkSanity is available at: https://github.com/ravel-lab/kSanity

bioinformatics↗

bioRxiv2025

StrainFacts accurately quantifies both endogenous and live biotherapeutic product strain abundances in simulated and clinical vaginal microbiota samples

Live biotherapeutic products (LBPs) deliver microbial strains to modulate the host microbiota in order to promote health or treat and prevent disease. Since endogenous strains are already present, accurately evaluating LBP efficacy and mechanism of action requires distinguishing administered from endogenous strains. Although computational tools exist for inferring strains from short-read metagenomic data, few have been rigorously tested in the context of LBP treatment. Here, we assess the ability of StrainFacts, a computational tool for inferring strains from short-read metagenomic data, to estimate strain abundances and genotypes of endogenous and administered strains. We performed a simulation study of a single-strain LBP trial, modeling serial samples across a range of administered strain abundance, co-occurring endogenous strains, and sequencing depths. We found that StrainFacts accurately estimated both LBP and endogenous strain abundances and genotypes within simulated samples. We further validated methods using human vaginal microbiota samples spiked with CTV-05, the Lactobacillus crispatus strain contained in the LBP LACTIN-V, which has been shown to reduce recurrent bacterial vaginosis. Our findings demonstrate that StrainFacts can robustly assess LBP and endogenous strain colonization, abundance, and dynamics in simulated and experimental microbiota samples, supporting its utility as an analysis tool for vaginal LBP therapeutic trial data.

bioinformatics↗

bioRxiv2021

Rapid evolutionary turnover of mobile genetic elements drives microbial resistance to viruses

Although it is generally accepted that viruses (phages) drive bacterial evolution, how these dynamics play out in the wild remains poorly understood. Here we show that the arms race between phages and their hosts is mediated by large and highly diverse mobile genetic elements. These phage-defense elements display exceedingly fast evolutionary turnover, resulting in differential phage susceptibility among clonal bacterial strains while phage receptors remain invariant. Protection afforded by multiple elements is cumulative, and a single bacterial genome can harbor as many as 18 putative phage-defense elements. Overall, elements account for 90% of the flexible genome amongst closely related strains. The rapid turnover of these elements demonstrates that phage resistance is unlinked from other genomic features and that resistance to phage therapy might be as easily acquired as antibiotic resistance.

microbiology↗