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首页> 外文期刊>Infection and immunity >The Cpx Stress Response System Potentiates the Fitness and Virulence of Uropathogenic Escherichia coli
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The Cpx Stress Response System Potentiates the Fitness and Virulence of Uropathogenic Escherichia coli

机译：Cpx应激反应系统增强了致病性大肠杆菌的适应性和毒力。

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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.
机译：泌尿道致病性大肠埃希菌（UPEC）菌株是泌尿道感染的主要原因，代表了地球上最广泛和最成功的病原体之一。为了在尿道内定植并持续存在，UPEC必须能够感知并适当应对环境压力，其中许多压力会损害细菌的包膜。 Cpx两组分包膜应激反应系统由内膜组氨酸激酶CpxA，胞质反应调节剂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，我们显示Cpx系统对于两种参考UPEC菌株（膀胱炎分离株UTI89和尿嘧啶分离物CFT073）的适应性和毒力至关重要。具体来说，删除cpxRA操纵子会损害UTI89在鼠膀胱中定植的能力，并大大降低斑马鱼胚胎在全身和局部感染过程中CFT073的毒力。这些缺陷与UTI89对宿主细胞的侵袭减少，两种菌株对补体介导的杀伤和氨基糖苷类抗生素丁胺卡那霉素的敏感性增加有关。用cpxP缺失突变体获得的结果更为复杂，这表明该良好保守的辅助因子具有可变的菌株依赖性和利基特异性要求。

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