Schreiber Henry L, Conover Matt S, Chou Wen-Chi, Hibbing Michael E, Manson Abigail L, Dodson Karen W, Hannan Thomas J, Roberts Pacita L, Stapleton Ann E, Hooton Thomas M, Livny Jonathan, Earl Ashlee M, Hultgren Scott J
Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Sci Transl Med. 2017 Mar 22;9(382). doi: 10.1126/scitranslmed.aaf1283.
Urinary tract infections (UTIs) are caused by uropathogenic (UPEC) strains. In contrast to many enteric pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.
尿路感染（UTIs）由尿路致病性（UPEC）菌株引起。与许多肠道菌群不同，尚未鉴定出UPEC菌株的基因特征。我们使用从频繁复发性尿路感染女性尿液中收集的分离株进行了一项高分辨率比较基因组研究。这些分离株在基因上具有多样性，其尿路致病性（即它们在膀胱炎小鼠模型中感染膀胱的能力）也各不相同。我们没有发现任何一组基因，包括先前定义的假定尿路致病因子（PUFs），能够预测尿路致病性。此外，在一些患者中，导致复发性尿路感染的菌株比被替代的菌株具有更少的PUFs。在小鼠的竞争性实验感染中，替代菌株比被替代菌株更有效地定殖于小鼠膀胱。尽管缺乏明确的尿路致病性基因组特征，但比较转录组学和表型分析表明，培养过程中关键保守功能（如运动性和代谢）的表达可用于预测随后在小鼠膀胱中的定殖情况。总之，我们的研究结果表明，尿路感染的风险和结果可能由宿主易感性与不同细菌菌株的尿路致病潜力之间的复杂相互作用所决定。
