Garofalo Corinne K, Hooton Thomas M, Martin Steven M, Stamm Walter E, Palermo Joseph J, Gordon Jeffrey I, Hultgren Scott J
Department of Molecular Microbiology, Box 8230, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Infect Immun. 2007 Jan;75(1):52-60. doi: 10.1128/IAI.01123-06. Epub 2006 Oct 30.
Nearly 50% of women experience at least one urinary tract infection (UTI) in their lifetime. Studies with mice have revealed that uropathogenic Escherichia coli (UPEC) isolates invade superficial umbrella cells that line the bladder, allowing them to find a safe haven and subvert clearance by innate host responses. Rapid intracellular replication results in the formation of distinctive intracellular bacterial communities (IBCs). In this study, we evaluated whether UPEC strains cultured from the urine of women and classified as causing acute cystitis, recurrent cystitis, asymptomatic bacteriuria, or pyelonephritis could progress through the IBC cascade in a well-characterized mouse model of cystitis. Of 18 UPEC isolates collected from women, 15 formed IBCs. Variations in the size, number, and kinetics of IBC formation were observed with strains isolated from women with different clinical syndromes. Two of the three isolates that did not form IBCs when inoculated alone were able to do so when coinoculated with an isolate that was capable of generating IBCs. The mixed infections dramatically altered the behavior of the coinfecting bacteria relative to their behavior in a single infection. The study also showed that mice with five different genetic backgrounds can support IBC formation. Although UPEC isolates differ genetically in their virulence factors, the majority of UPEC isolates from different types of UTI proceed through the IBC pathway, confirming the generality of IBCs in UTI pathogenesis in mice.
近50%的女性在其一生中至少经历过一次尿路感染(UTI)。对小鼠的研究表明,尿路致病性大肠杆菌(UPEC)分离株会侵入膀胱内衬的表层伞细胞,使其能够找到一个安全的藏身之所,并逃避宿主先天免疫反应的清除。细菌在细胞内快速复制会导致形成独特的细胞内细菌群落(IBCs)。在本研究中,我们评估了从女性尿液中培养的、被分类为引起急性膀胱炎、复发性膀胱炎、无症状菌尿或肾盂肾炎的UPEC菌株,是否能在一个特征明确的膀胱炎小鼠模型中经历IBC级联反应。从女性中收集的18株UPEC分离株中,有15株形成了IBCs。观察到从患有不同临床综合征的女性中分离出的菌株在IBC形成的大小、数量和动力学方面存在差异。单独接种时未形成IBCs的三株分离株中的两株,与一株能够产生IBCs的分离株共同接种时能够形成IBCs。混合感染相对于单一感染显著改变了共感染细菌的行为。该研究还表明,具有五种不同遗传背景的小鼠都能支持IBC的形成。尽管UPEC分离株在毒力因子方面存在基因差异,但大多数来自不同类型UTI的UPEC分离株都能通过IBC途径,这证实了IBCs在小鼠UTI发病机制中的普遍性。