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Variability in cell division among anatomical sites shapes Escherichia coli antibiotic survival in a urinary tract infection mouse model
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2024-05-16 , DOI: 10.1016/j.chom.2024.04.015
Ariane Amoura , Claire Pistien , Camille Chaligné , Sara Dion , Mélanie Magnan , Antoine Bridier-Nahmias , Alexandra Baron , Françoise Chau , Emmanuel Bourgogne , Minh Le , Erick Denamur , Molly A. Ingersoll , Bruno Fantin , Agnès Lefort , Imane El Meouche

Urinary tract infection (UTI), mainly caused by Escherichia coli, are frequent and have a recurrent nature even after antibiotic treatment. Potential bacterial escape mechanisms include growth defects, but probing bacterial division in vivo and establishing its relation to the antibiotic response remain challenging. Using a synthetic reporter of cell division, we follow the temporal dynamics of cell division for different E. coli clinical strains in a UTI mouse model with and without antibiotics. We show that more bacteria are actively dividing in the kidneys and urine compared with the bladder. Bacteria that survive antibiotic treatment are consistently non-dividing in three sites of infection. Additionally, we demonstrate how both the strain in vitro persistence profile and the microenvironment impact infection and treatment dynamics. Understanding the relative contribution of the host environment, growth heterogeneity, non-dividing bacteria, and antibiotic persistence is crucial to improve therapies for recurrent infections.



中文翻译:

尿路感染小鼠模型中解剖部位细胞分裂的变异影响大肠杆菌抗生素的存活

尿路感染(UTI)主要由大肠杆菌引起,即使在抗生素治疗后也很常见并且具有复发性。潜在的细菌逃逸机制包括生长缺陷,但探测体内细菌分裂并确定其与抗生素反应的关系仍然具有挑战性。使用细胞分裂的合成报告器,我们跟踪了使用和不使用抗生素的 UTI 小鼠模型中不同大肠杆菌临床菌株的细胞分裂的时间动态。我们发现,与膀胱相比,肾脏和尿液中活跃分裂的细菌更多。在抗生素治疗后存活下来的细菌在三个感染部位始终不分裂。此外,我们还展示了菌株体外持久性和微环境如何影响感染和治疗动态。了解宿主环境、生长异质性、不分裂细菌和抗生素持久性的相对影响对于改善复发性感染的治疗至关重要。

更新日期:2024-05-16
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