Sharon Belle M, Arute Amanda P, Nguyen Amber, Tiwari Suman, Bonthu Sri Snehita Reddy, Hulyalkar Neha V, Neugent Michael L, Araya Dennise Palacios, Dillon Nicholas A, Zimmern Philippe E, Palmer Kelli L, De Nisco Nicole J
bioRxiv. 2023 May 18:2023.05.18.541374. doi: 10.1101/2023.05.18.541374.
is the leading Gram-positive bacterial species implicated in urinary tract infection (UTI). An opportunistic pathogen, 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 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 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 with respect to 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 . Both genotypic and phenotypic analysis of antimicrobial resistance among urinary 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.
Urinary 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 , 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 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 adaptation to the female urinary tract.
是引起尿路感染（UTI）的主要革兰氏阳性细菌种类。作为一种机会致病菌，它是人类胃肠道（GIT）的共生菌，其在胃肠道中的存在是UTI的一个易感因素。人们对其在尿路（UT）中定殖和存活的机制了解甚少，尤其是在非复杂性或复发性UTI中。尿路与胃肠道不同，其特点是营养物质匮乏且存在独特的环境应激源。在本研究中，我们从主要为绝经后女性的尿液中分离并测序了37株临床菌株。我们生成了33个封闭基因组组装体和4个高度连续的草图组装体，并进行了比较基因组学研究，以确定相对于从人类胃肠道和血液中分离出的，在尿路中富集的遗传特征。系统发育分析揭示了尿路菌株之间的高度多样性，以及尿液和肠道分离株之间的亲缘关系比血液分离株更近。质粒复制子（rep）分型进一步强调了尿路与胃肠道之间可能的联系，确定了尿液和肠道之间有9种共享的rep类型。对尿路中抗菌药物耐药性的基因型和表型分析均显示，对一线UTI抗生素呋喃妥因和氟喹诺酮类药物耐药情况不常见，且无万古霉素耐药性。最后，我们确定了19个在尿路菌株中富集的候选基因，它们可能在适应尿路方面发挥作用。这些基因参与糖转运、钴胺素摄取、葡萄糖代谢以及基因表达的转录后调控等核心过程。
尿路感染（UTI）是一个全球性的健康问题，给医疗系统带来了沉重负担。女性受UTI的影响尤为严重，超过60%的女性在一生中至少经历过一次UTI。UTI可能会复发，尤其是在绝经后女性中，会导致生活质量下降，并可能引发危及生命的并发症。由于抗菌药物耐药率不断上升，迫切需要确定新的治疗靶点，因此了解病原体如何在尿路中定殖和存活至关重要。作为一种通常与UTI相关的细菌，如何适应尿路仍未得到充分研究。在这里，我们从绝经后女性尿液中分离出临床尿路菌株，生成了一组高质量的封闭基因组组装体，并结合详细的临床元数据，对可能介导尿路适应女性尿路的遗传因素进行了有力的比较基因组学研究。
