Biology subjects

Hulyalkar, N. V.

Publications and source records attributed to Hulyalkar, N. V..

3 recordsLinked to original sources

bioRxiv2023

Functional and genetic adaptations contributing to Enterococcus faecalis persistence in the female urinary tract

Enterococcus faecalis is the leading Gram-positive bacterial species implicated in urinary tract infection (UTI). An opportunistic pathogen, E. faecalis is a commensal of the human gastrointestinal tract (GIT) and its presence in the GIT is a predisposing factor for UTI. The mechanisms by which E. faecalis colonizes and survives in the urinary tract (UT) are poorly understood, especially in uncomplicated or recurrent UTI. The UT is distinct from the GIT and is characterized by a sparse nutrient landscape and unique environmental stressors. In this study, we isolated and sequenced a collection of 37 clinical E. faecalis strains from the urine of primarily postmenopausal women. We generated 33 closed genome assemblies and four highly contiguous draft assemblies and conducted a comparative genomics to identify genetic features enriched in urinary E. faecalis with respect to E. faecalis isolated from the human GIT and blood. Phylogenetic analysis revealed high diversity among urinary strains and a closer relatedness between urine and gut isolates than blood isolates. Plasmid replicon (rep) typing further underscored possible UT-GIT interconnection identifying nine shared rep types between urine and gut E. faecalis. Both genotypic and phenotypic analysis of antimicrobial resistance among urinary E. faecalis revealed infrequent resistance to front-line UTI antibiotics nitrofurantoin and fluoroquinolones and no vancomycin resistance. Finally, we identified 19 candidate genes enriched among urinary strains that may play a role in adaptation to the UT. These genes are involved in the core processes of sugar transport, cobalamin import, glucose metabolism, and post-transcriptional regulation of gene expression. IMPORTANCEUrinary tract infection (UTI) is a global health issue that imposes substantial burden on healthcare systems. Women are disproportionately affected by UTI with >60% of women experiencing at least one UTI in their lifetime. UTIs can recur, particularly in postmenopausal women, leading to diminished quality of life and potentially life-threatening complications. Understanding how pathogens colonize and survive in the urinary tract is necessary to identify new therapeutic targets that are urgently needed due to rising rates of antimicrobial resistance. How Enterococcus faecalis, a bacterium commonly associated with UTI, adapts to the urinary tract remains understudied. Here, we generated a collection of high-quality closed genome assemblies of clinical urinary E. faecalis isolated from the urine of postmenopausal women that we used alongside detailed clinical metadata to perform a robust comparative genomic investigation of genetic factors that may mediate urinary E. faecalis adaptation to the female urinary tract.

microbiology↗

bioRxiv2023

Urinary Glycosaminoglycans are Associated with Recurrent UTI and Urobiome Ecology in Postmenopausal Women

Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides composed of repeating disaccharide units of uronic acid and amino sugars. The luminal surface of the bladder epithelium is coated with a GAG layer. These urothelial GAGs are thought to provide a protective barrier and serve as a potential interaction site with the urinary microbiome (urobiome). Previous studies have profiled urinary GAG composition in mixed cohorts, but the urinary GAG composition in postmenopausal women remains undefined. To investigate the relationship between GAGs and recurrent UTI (rUTI), we profiled urinary GAGs in a controlled cohort of postmenopausal women. We found that chondroitin sulfate (CS) is the major urinary GAG in postmenopausal women and that urinary CS was elevated in women with active rUTI. We also associated urinary GAGs with urobiome composition and identified bacterial species that significantly associated with urinary GAG concentration. Corynebacterium amycolatum, Porphyromonas somerae, and Staphylococcus pasteuri were positively associated with heparin sulfate or hyaluronic acid and bacterial species associated with vaginal dysbiosis were negatively correlated to urinary CS. Altogether, this work defines changes in urinary GAG composition associated with rUTI and identifies new associations between urinary GAGs and the urobiome that may play a role in rUTI pathobiology.

biochemistry↗

bioRxiv2021

Recurrent urinary tract infection and estrogen shape the taxonomic ecology and functional potential of the postmenopausal urobiome

Community-acquired urinary tract infection (UTI) is among the most common bacterial infections observed in humans. Postmenopausal women are a rapidly growing and underserved demographic group who are severely affected by recurrent UTI (rUTI) with a >50% recurrence rate. In this population, rUTI can persist for years, reducing quality of life and imposing a significant healthcare burden. rUTI is most often treated by antibiotics, but development of antibiotic resistance and allergy limit therapeutic options. The female urinary microbiome (urobiome) has been identified as a key component of the urogenital environment. However, compositional and functional changes in the urobiome underlying rUTI susceptibility in postmenopausal women are not well understood. Here, we used a controlled, cross-sectional cohort of postmenopausal women, to interrogate changes in urobiome structure and function linked to rUTI susceptibility by whole genome metagenomic sequencing (WGMS), advanced urine culture, estrogen metabolite profiling, and antibiotic sensitivity testing. Overall, we detected 276 bacterial, archaeal, and fungal species representing 106 genera. We find a putative commensal population consisting of species known to protect against bacterial vaginosis, such as Lactobacillus crispatus, within the urobiome of postmenopausal women who do not experience UTI. Integration of clinical metadata detected an almost exclusive enrichment of lactobacilli, including L. crispatus and L. vaginalis, in women taking estrogen hormone therapy (EHT). Integrating quantitative metabolite profiling of urinary estrogens with WGMS, we observed robust correlations between urobiome taxa, such as Bifidobacterium breve and L. crispatus, and urinary estrogen conjugate concentrations in women with no history of UTI that were absent in women with rUTI history. We further used functional metagenomic profiling and patient-derived isolate phenotyping to identify microbial metabolic pathways, antimicrobial resistance genes (ARGs), and clinically relevant antimicrobial resistance phenotypes enriched between disease-states. Our data indicate that distinct urobiome metabolic and ARG signatures are associated with current rUTI status and history. Importantly, we observed that rUTI history leaves an imprint of enriched ARGs even in women not currently experiencing UTI. Taken together, our data suggests that rUTI history and estrogen strongly shape the functional and taxonomic composition of the urobiome in postmenopausal women.

microbiology↗