背景:尿路感染(UTI)是常见的细菌感染,主要由尿路致病性大肠杆菌(UPEC)引起,导致严重的健康问题和经济负担。尽管抗生素在治疗UPEC感染方面是有效的,抗生素抗性菌株的增加阻碍了它们的功效。因此,为新的抗菌方法确定新的细菌靶标是至关重要的。维持UPEC完全毒力所需的细菌因子是潜在的靶标。MepM,大肠杆菌中的内肽酶,参与肽聚糖的生物发生,细菌包膜的主要结构。鉴于细菌包膜在感染期间面对敌对的宿主环境,MepM的功能可能对UPEC的毒力至关重要。本研究旨在探讨MepM在UPEC发病机制中的作用。
结果:MepM缺乏显著影响UPEC在尿液和巨噬细胞内的存活。此外,这种缺陷阻碍了细菌到丝状的形状转换,这种转换以帮助UPEC在感染期间逃避吞噬作用而闻名。此外,由于MepM缺乏,UPEC运动下调。因此,与野生型UPEC相比,mepM突变体在小鼠模型中引起UTI的适应性显着降低。
结论:这项研究提供了肽聚糖内肽酶MepM在UPEC引起UTI的全毒力中的重要作用的第一个证据。MepM对UPEC发病机制的贡献可能源于其在维持抵抗尿液和免疫细胞介导的杀伤能力方面的关键作用,促进形态学转换,和持续的运动。因此,MepM是新型抗微生物策略的有希望的候选靶标。
BACKGROUND: Urinary tract infections (UTIs) are common bacterial infections, primarily caused by uropathogenic Escherichia coli (
UPEC), leading to significant health issues and economic burden. Although antibiotics have been effective in treating
UPEC infections, the rise of antibiotic-resistant strains hinders their efficacy. Hence, identifying novel bacterial targets for new antimicrobial approaches is crucial. Bacterial factors required for maintaining the full virulence of
UPEC are the potential target. MepM, an endopeptidase in E. coli, is involved in the biogenesis of peptidoglycan, a major structure of bacterial envelope. Given that the bacterial envelope confronts the hostile host environment during infections, MepM\'s function could be crucial for UPEC\'s virulence. This study aims to explore the role of MepM in
UPEC pathogenesis.
RESULTS: MepM deficiency significantly impacted UPEC\'s survival in urine and within macrophages. Moreover, the deficiency hindered the bacillary-to-filamentous shape switch which is known for aiding UPEC in evading phagocytosis during infections. Additionally,
UPEC motility was downregulated due to MepM deficiency. As a result, the mepM mutant displayed notably reduced fitness in causing UTIs in the mouse model compared to wild-type UPEC.
CONCLUSIONS: This study provides the first evidence of the vital role of peptidoglycan endopeptidase MepM in UPEC\'s full virulence for causing UTIs. MepM\'s contribution to UPEC pathogenesis may stem from its critical role in maintaining the ability to resist urine- and immune cell-mediated killing, facilitating the morphological switch, and sustaining motility. Thus, MepM is a promising candidate target for novel antimicrobial strategies.