Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Chongqing Healthcare Security Administration, Chongqing, 401120, China.
Microb Pathog. 2021 Feb;151:104748. doi: 10.1016/j.micpath.2021.104748. Epub 2021 Jan 21.
Uropathogenic Escherichia coli (UPEC) is the most prevalent causative agent of urinary tract infections (UTIs). The pathogenicity of UPEC relies on the expression of virulence factors which could be regulated by intercellular signal molecules. Our previous study found that sub-minimal inhibitory concentration ceftazidime (sub-MIC CAZ) could inhibit the biofilm formation of E. coli by luxS/AI-2 or indole. Therefore, we speculated that sub-MIC CAZ might affect the pathogenic capacity of UPEC. In this study, the results showed that sub-MIC CAZ could significantly inhibit the adhesion ability, biofilm formation and swimming and swarming motilities of UPEC isolated from recurrent UTI patient. Meanwhile, obvious decreased hemolytic activity and cytotoxicity were observed in CAZ-pretreated UPEC. Furthermore, qRT-PCR results confirmed the downregulating ability of CAZ on the expression of adhesion genes, motility genes, toxin gene and signal molecule synthesis genes, which are important for virulence and biofilm formation of UPEC. Pre-treatment of UPEC with sub-MIC CAZ resulted in the reduced adhesion to human bladder epithelial cell 5637 and the decreased numbers of intracellular bacterial communities in cells. Consistent with the results in vitro, the pretreatment of CAZ resulted in the reduction of UPEC load in the bladder and the less severity of UPEC-induced inflammation compared with control group. The present study results indicated that sub-MIC CAZ could decrease the pathogenicity of UPEC and might be served as an effective antimicrobial agent to combat recurrent UTI caused by UPEC.
尿路致病性大肠杆菌（UPEC）是尿路感染（UTI）最常见的病原体。UPEC 的致病性依赖于毒力因子的表达，这些因子可以被细胞间信号分子调节。我们之前的研究发现，亚最小抑菌浓度头孢他啶（sub-MIC CAZ）可以通过 luxS/AI-2 或吲哚抑制大肠杆菌生物膜的形成。因此，我们推测 sub-MIC CAZ 可能会影响 UPEC 的致病能力。在这项研究中，结果表明 sub-MIC CAZ 可显著抑制复发性尿路感染患者分离的 UPEC 的黏附能力、生物膜形成和泳动和群集运动能力。同时，在 CAZ 预处理的 UPEC 中观察到明显降低的溶血活性和细胞毒性。此外，qRT-PCR 结果证实 CAZ 对黏附基因、运动基因、毒素基因和信号分子合成基因表达具有下调能力，这些基因对 UPEC 的毒力和生物膜形成至关重要。用 sub-MIC CAZ 预处理 UPEC 可降低其与人膀胱上皮细胞 5637 的黏附能力和细胞内细菌群落的数量。与体外结果一致，与对照组相比，CAZ 预处理可降低膀胱中 UPEC 的载量并减轻 UPEC 引起的炎症程度。本研究结果表明，sub-MIC CAZ 可降低 UPEC 的致病性，可能作为一种有效的抗菌剂来对抗由 UPEC 引起的复发性 UTI。
