Division of Microbiology and Immunology, Pathology Department, University of Utah, Salt Lake City, Utah, USA.
Infect Immun. 2013 May;81(5):1450-9. doi: 10.1128/IAI.01213-12. Epub 2013 Feb 19.
Strains of uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infections, representing one of the most widespread and successful groups of pathogens on the planet. To colonize and persist within the urinary tract, UPEC must be able to sense and respond appropriately to environmental stresses, many of which can compromise the bacterial envelope. The Cpx two-component envelope stress response system is comprised of the inner membrane histidine kinase CpxA, the cytosolic response regulator CpxR, and the periplasmic auxiliary factor CpxP. Here, by using deletion mutants along with mouse and zebrafish infection models, we show that the Cpx system is critical to the fitness and virulence of two reference UPEC strains, the cystitis isolate UTI89 and the urosepsis isolate CFT073. Specifically, deletion of the cpxRA operon impaired the ability of UTI89 to colonize the murine bladder and greatly reduced the virulence of CFT073 during both systemic and localized infections within zebrafish embryos. These defects coincided with diminished host cell invasion by UTI89 and increased sensitivity of both strains to complement-mediated killing and the aminoglycoside antibiotic amikacin. Results obtained with the cpxP deletion mutants were more complicated, indicating variable strain-dependent and niche-specific requirements for this well-conserved auxiliary factor.
尿路致病性大肠杆菌（UPEC）菌株是尿路感染的主要原因，是地球上分布最广泛和最成功的病原体之一。为了在泌尿道中定植和持续存在，UPEC 必须能够感知和适当地对环境应激作出反应，其中许多应激会破坏细菌的包膜。Cpx 双组分包膜应激反应系统由内膜组氨酸激酶 CpxA、胞质响应调节剂 CpxR 和周质辅助因子 CpxP 组成。在这里，通过使用缺失突变体以及小鼠和斑马鱼感染模型，我们表明 Cpx 系统对两种参考 UPEC 菌株（膀胱炎分离株 UTI89 和尿脓毒症分离株 CFT073）的适应性和毒力至关重要。具体来说，cpxRA 操纵子的缺失削弱了 UTI89 在小鼠膀胱中定植的能力，并大大降低了 CFT073 在斑马鱼胚胎全身和局部感染期间的毒力。这些缺陷与 UTI89 宿主细胞侵袭能力下降以及两种菌株对补体介导杀伤和氨基糖苷类抗生素阿米卡星的敏感性增加有关。用 cpxP 缺失突变体获得的结果更加复杂，表明该保守辅助因子存在菌株依赖性和特定生态位的不同需求。
