Competitive fitness of asymptomatic bacteriuria E. coli strain 83972 against uropathogens in human urine.

IF 2.9 3区 医学 Q3 IMMUNOLOGY Infection and Immunity Pub Date : 2024-06-11 Epub Date: 2024-05-23 DOI:10.1128/iai.00173-24
Iris George, Manivannan Sivaperuman Kalairaj, Philippe E Zimmern, Taylor H Ware, Sargurunathan Subashchandrabose
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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.

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无症状菌尿大肠杆菌 83972 株对人体尿液中尿路病原体的竞争适应性。
尿路感染(UTI)是全球最常见的细菌感染之一。尿路感染的主要致病菌是尿路致病性大肠杆菌(UPEC)。由于尿路病原体对抗菌素的耐药性不断增加,因此迫切需要针对尿路感染的新型预防和治疗策略。ABU 83972 是一种无症状菌尿症致病大肠杆菌菌株,可通过抑制 UPEC 的定植来预防 UTI。然而,ABU 83972 对 UPEC 的竞争和生长抑制的性质尚不清楚,这也是我们研究的主题。在此,我们描述了 ABU 83972 和尿路病原体在人尿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,将 ABU 83972 和尿路病原体以 1:1 的比例接种到人尿和各种培养基中,并测定它们的相对丰度。在人体尿液中,ABU 83972 与 UPEC 和其他尿路病原体竞争,培养 24 小时后,ABU 83972 的数量达到总数量的 90%。相比之下,UPEC 在 LB 和 M9 最小培养基中对 ABU 83972 的竞争能力更强,在小鼠膀胱中的定殖能力优于 ABU 83972。由于工程活体材料(ELMs)可用于将感兴趣的生物体保留在特定位置,因此我们开发了含有 ABU 83972 的 ELMs,它能有效地在人类尿液中战胜 UPEC。总之,我们的工作证实 ABU 83972 能以环境和细胞密度依赖性的方式战胜 UPEC,突出了人尿中的代谢物和营养物质作为 ABU 83972 竞争力决定因素的重要性。
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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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