The Cpx Stress Response System Potentiates the Fitness and Virulence of Uropathogenic Escherichia coli
The Cpx Stress Response System Potentiates the Fitness and Virulence of Uropathogenic Escherichia coli
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DOI：
10.1128/iai.01213-12
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Mulvey, Matthew A.
中科院分区：
文献类型：
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作者：
Debnath, Irina;Norton, J. Paul;Mulvey, Matthew A.
尿路致病性大肠杆菌 (UPEC) 菌株是尿路感染的主要原因，是地球上最广泛、最成功的病原体群之一。为了在泌尿道内定殖并持续存在，UPEC 必须能够感知环境压力并做出适当的反应，其中许多环境压力会损害细菌包膜。 Cpx二元包膜应激反应系统由内膜组氨酸激酶CpxA、胞质反应调节因子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 系统对于两种参考 UPEC 菌株（膀胱炎分离株 UTI89 和尿脓毒株 CFT073）的适应性和毒力至关重要。具体来说，cpxRA操纵子的缺失损害了UTI89定植于小鼠膀胱的能力，并大大降低了斑马鱼胚胎内全身和局部感染期间CFT073的毒力。这些缺陷与 UTI89 宿主细胞侵袭减少以及两种菌株对补体介导的杀伤和氨基糖苷类抗生素阿米卡星的敏感性增加相一致。 cpxP 缺失突变体获得的结果更加复杂，表明对这种高度保守的辅助因子的可变菌株依赖性和生态位特异性要求。
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.