Horizontal Transfer of the Salmonella enterica Serovar Infantis Resistance and Virulence Plasmid pESI to the Gut Microbiota of Warm-Blooded Hosts.
Horizontal Transfer of the Salmonella enterica Serovar Infantis Resistance and Virulence Plasmid pESI to the Gut Microbiota of Warm-Blooded Hosts.
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DOI：
10.1128/mbio.01395-16
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发表时间：
2016-09-06
期刊：
影响因子：
6.4
通讯作者：
Gal-Mor O
中科院分区：
文献类型：
--
作者：
Aviv G;Rahav G;Gal-Mor O
婴儿肠道沙门氏菌（Salmonella enterica serovar Infantis）是世界范围内流行的沙门氏菌之一。最近，我们发现婴儿链球菌在以色列的出现是由于获得了一个独特的大质粒（pESI），赋予多重耐药性和增加的毒力表型。在这里，我们阐明生态，传输特性，和调节pESI。我们发现，尽管它的大尺寸（~280 kb），pESI不施加显着的体外代谢负担，它最近已被固定在国内婴儿链球菌人口。pESI结合及其菌毛（pESI）基因的转录在环境温度（27°C）和≥1%胆汁下受到抑制，但在37 - 41°C温度、氧化应激、中等渗透压和温血动物肠道环境特征微需氧条件下增加。pESI编码的蛋白质TraB和氧稳态调节因子Fnr被鉴定为pESI缀合的转录调节因子。使用小鼠模型，我们表明婴儿链球菌感染后，pESI可以水平转移到肠道微生物群，包括大肠杆菌菌株。还观察到pESI可能转移到革兰氏阳性小鼠微生物群物种，特别是罗伊氏乳杆菌中，但不持久。此外，在胃肠道感染的情况下，pESI被证明可以进一步从肠道微生物群传播到鼠伤寒沙门氏菌。这些发现展示了自私的临床相关大质粒向微生物群和从微生物群分布的能力，并表明微生物群作为移动的遗传元件的储存库和中间体在细菌和病原菌之间的抗性和毒力基因的传播中的被忽视的作用。质粒接合在微生物进化中起着关键作用，使得能够获得新的表型，包括抗性和毒力。婴儿肠道沙门氏菌（Salmonella enterica serovar Infantis）是世界范围内普遍存在的沙门氏菌之一，也是食源性感染的主要原因。以前，我们表明，婴儿链球菌在以色列的出现涉及获得一个独特的大质粒（pESI），赋予多药耐药性和增加的毒力表型。最近，在意大利发现了另一种携带pESI样质粒的婴儿链球菌菌株，这表明pESI的获得可能是全球不同新生婴儿链球菌种群的共同点。这种质粒传播到其他菌株或细菌物种是一个令人担忧的情况。了解临床相关质粒的生态学、调节和传播特性以及微生物群在其传播中的作用，为解释新的致病性和耐药生物型的出现提供了一种新的机制，并可能有助于制定适当的监测和预防措施。
Salmonella enterica serovar Infantis is one of the prevalent salmonellae worldwide. Recently, we showed that the emergence of S. Infantis in Israel was facilitated by the acquisition of a unique megaplasmid (pESI) conferring multidrug resistance and increased virulence phenotypes. Here we elucidate the ecology, transmission properties, and regulation of pESI. We show that despite its large size (~280 kb), pESI does not impose a significant metabolic burden in vitro and that it has been recently fixed in the domestic S. Infantis population. pESI conjugation and the transcription of its pilus (pil) genes are inhibited at the ambient temperature (27°C) and by ≥1% bile but increased under temperatures of 37 to 41°C, oxidative stress, moderate osmolarity, and the microaerobic conditions characterizing the intestinal environment of warm-blooded animals. The pESI-encoded protein TraB and the oxygen homeostasis regulator Fnr were identified as transcriptional regulators of pESI conjugation. Using the mouse model, we show that following S. Infantis infection, pESI can be horizontally transferred to the gut microbiota, including to commensal Escherichia coli strains. Possible transfer, but not persistence, of pESI was also observed into Gram-positive mouse microbiota species, especially Lactobacillus reuteri. Moreover, pESI was demonstrated to further disseminate from gut microbiota to S. enterica serovar Typhimurium, in the context of gastrointestinal infection. These findings exhibit the ability of a selfish clinically relevant megaplasmid to distribute to and from the microbiota and suggest an overlooked role of the microbiota as a reservoir of mobile genetic elements and intermediator in the spread of resistance and virulence genes between commensals and pathogenic bacteria. Plasmid conjugation plays a key role in microbial evolution, enabling the acquisition of new phenotypes, including resistance and virulence. Salmonella enterica serovar Infantis is one of the ubiquitous salmonellae worldwide and a major cause of foodborne infections. Previously, we showed that the emergence of S. Infantis in Israel has involved the acquisition of a unique megaplasmid (pESI) conferring multidrug resistance and increased virulence phenotypes. Recently, the emergence of another S. Infantis strain carrying a pESI-like plasmid was identified in Italy, suggesting that the acquisition of pESI may be common to different emergent S. Infantis populations globally. Transmission of this plasmid to other strains or bacterial species is an alarming scenario. Understanding the ecology, regulation, and transmission properties of clinically relevant plasmids and the role of the microbiota in their spreading offers a new mechanism explaining the emergence of new pathogenic and resistant biotypes and may assist in the development of appropriate surveillance and prevention measures.