The Infectious Diseases Research Laboratory, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
Environ Microbiol. 2014 Apr;16(4):977-94. doi: 10.1111/1462-2920.12351. Epub 2014 Jan 7.
Of all known Salmonella enterica serovars, S. Infantis is one of the most commonly isolated and has been recently emerging worldwide. To understand the recent emergence of S. Infantis in Israel, we performed extensive comparative analyses between pre-emergent and the clonal emergent S. Infantis populations. We demonstrate the fixation of adaptive mutations in the DNA gyrase (gyrA) and nitroreductase (nfsA) genes, conferring resistance to quinolones and nitrofurans, respectively, and the carriage of an emergent-specific plasmid, designated pESI. This self-transferred episome is a mosaic megaplasmid (∼280 kb), which increases bacterial tolerance to environmental mercury (mer operon) and oxidative stress, and provides further resistance to tetracycline, sulfamethoxazole and trimethoprim, most likely due to the presence of tetRA, sulI and dfrA genes respectively. Moreover, pESI carries the yersiniabactin siderophore system and two novel chaperone-usher fimbriae. In vitro studies established that pESI conjugation into a plasmidless S. Infantis strain results in superior biofilm formation, adhesion and invasion into avian and mammalian host cells. In vivo mouse infections demonstrated higher pathogenicity and increased intestinal inflammation caused by an S. Infantis strain harboring pESI compared with the plasmidless parental strain. Our results indicate that the presence of pESI that was found only in the emergent population of S. Infantis in Israel contributes significantly to antimicrobials tolerance and pathogenicity of its carrier. It is highly likely that pESI plays a key role in the successful spread of the emergent clone that replaced the local S. Infantis community in the short time of only 2-3 years.
在所有已知的沙门氏菌血清型中，婴儿沙门氏菌是最常分离到的血清型之一，并且最近在全球范围内出现。为了了解婴儿沙门氏菌在以色列的近期出现，我们对早期出现的和克隆性出现的婴儿沙门氏菌群体进行了广泛的比较分析。我们证明了 DNA 拓扑异构酶（gyrA）和硝基还原酶（nfsA）基因中的适应性突变的固定，分别赋予对喹诺酮类和硝基呋喃类的抗性，以及携带一个新兴特异性质粒，命名为 pESI。这个自我转移的附加体是一个镶嵌的巨大质粒（约 280kb），它增加了细菌对环境汞（mer 操纵子）和氧化应激的耐受性，并提供了对四环素、磺胺甲恶唑和甲氧苄啶的进一步抗性，这很可能是由于tetRA、sulI 和 dfrA 基因的存在。此外，pESI 携带耶尔森菌铁载体系统和两个新的伴侣菌毛。体外研究表明，pESI 接合到无质粒的婴儿沙门氏菌菌株中，导致更好的生物膜形成、黏附和侵袭禽和哺乳动物宿主细胞。体内小鼠感染实验表明，与无质粒亲本菌株相比，携带 pESI 的婴儿沙门氏菌菌株引起的致病性更高，肠道炎症增加。我们的结果表明，仅在以色列婴儿沙门氏菌的新兴群体中发现的 pESI 的存在，显著促进了其载体对抗微生物药物的耐受性和致病性。极有可能的是，pESI 在新兴克隆的成功传播中发挥了关键作用，该克隆在短短 2-3 年内取代了当地的婴儿沙门氏菌群体。
