PDF(Pubmed)
Abstract：
Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.
摘要：
尿路感染（UTI）是全球最常见的细菌感染之一。UTI的主要致病因子是尿路致病性大肠杆菌(UPEC)。由于尿病原体中抗菌素耐药性的发生率增加，因此迫切需要针对UTI的新型预防和治疗策略。ABU83972，一种无症状的细菌尿症引起的大肠杆菌菌株，通过抑制UPEC的定植来预防UTI。然而,ABU83972对UPEC的竞争和生长抑制的性质尚不清楚，这是我们调查的主题。这里,我们表征了ABU83972和尿路病原体在人尿液和实验室培养基中的生长动力学。接下来,我们进行了一系列竞争性共培养实验，其中ABU83972和尿路病原体以1：1的比例接种在人尿和各种培养基中，并确定了它们的相对丰度。在人体尿液中，ABU83972胜过UPEC和其他尿路病原体，孵化24小时后达到总人口的90％。相比之下,UPEC在LB和M9基本培养基中胜过ABU83972，并且在小鼠膀胱中表现出比ABU83972更好的定植。由于工程活体材料（ELM）可用于将感兴趣的生物体保留在特定位置，我们开发了含有ABU83972的ELM,其在人尿中的竞争效果优于UPEC.总之,我们的工作确定ABU83972以环境和细胞密度依赖的方式胜过UPEC，强调人体尿液中发现的代谢物和营养素作为ABU83972竞争适应性决定因素的重要性。
