Abstract：
The bacterial species Salmonella enterica (S. enterica) is a highly diverse pathogen containing more than 2600 distinct serovars, which can infect a wide range of animal and human hosts. Recent global emergence of multidrug resistant strains, from serovars Infantis and Muenchen is associated with acquisition of the epidemic megaplasmid, pESI that augments antimicrobial resistance and pathogenicity. One of the main pESI\'s virulence factors is the potent iron uptake system, yersiniabactin encoded by fyuA, irp2-irp1-ybtUTE, ybtA, and ybtPQXS gene cluster. Here we show that yersiniabactin, has an underappreciated distribution among different S. enterica serovars and subspecies, integrated in their chromosome or carried by different conjugative plasmids, including pESI. While the genetic organization and the coding sequence of the yersiniabactin genes are generally conserved, a 201-bp insertion sequence upstream to ybtA, was identified in pESI. Despite this insertion, pESI-encoded yersiniabactin is regulated by YbtA and the ancestral Ferric Uptake Regulator (Fur), which binds directly to the ybtA and irp2 promoters. Furthermore, we show that yersiniabactin genes are specifically induced during the mid-late logarithmic growth phase and in response to iron-starvation or hydrogen peroxide. Concurring, yersiniabactin was found to play a previously unknown role in oxidative stress tolerance and to enhance intestinal colonization of S. Infantis in mice. These results indicate that yersiniabactin contributes to Salmonella fitness and pathogenicity in vivo and is likely to play a role in the rapid dissemination of pESI among globally emerging Salmonella lineages.
摘要：
肠道沙门氏菌(S.enterica)是一种高度多样化的病原体，含有超过2600种不同的血清型，可以感染广泛的动物和人类宿主。最近全球出现的多重耐药菌株，从Infantis和Muenchen的血清型与流行病大质粒的获得有关，pESI增强抗菌素耐药性和致病性。pESI的主要毒力因子之一是有效的铁摄取系统，由fyuA编码的yersiniabactin，irp2-irp1-ybtUTE,ybtA,和ybtPQXS基因簇。在这里我们展示了耶尔西尼阿巴汀，在不同的肠链球菌血清变型和亚种中分布被低估，整合在他们的染色体中或由不同的共轭质粒携带，包括PESI。虽然yersiniabactin基因的遗传组织和编码序列通常是保守的，ybtA上游的201bp插入序列，在pESI中被鉴定。尽管插入，pESI编码的Yersiniabactin受YbtA和祖先铁摄取调节剂（Fur）调节，它直接与ybtA和irp2启动子结合。此外，我们表明，yersiniabactin基因在对数生长中后期以及对铁饥饿或过氧化氢的反应中被特异性诱导。同意，发现耶尔森纳布汀在氧化应激耐受性中起着先前未知的作用，并增强了S.Infantis在小鼠中的肠道定植。这些结果表明，耶尔森纳布汀有助于沙门氏菌在体内的适应性和致病性，并且可能在全球新兴沙门氏菌谱系中pESI的快速传播中起作用。
