Abstract：
Salmonella enterica subsp. enterica serovar Typhimurium variant 4,[5],12:i:- (so called S. 4,[5],12:i:-) has rapidly become one of the most prevalent serovars in humans in Europe, with clinical cases associated with foodborne from pork products. The mechanisms, genetic basis and biofilms relevance by which S. 4,[5],12:i:- maintains and spreads its presence in pigs remain unclear. In this study, we examined the genetic basis of biofilm production in 78 strains of S. 4,[5],12:i:- (n = 57) and S. Typhimurium (n = 21), from human gastroenteritis, food products and asymptomatic pigs. The former showed a lower Specific Biofilm Formation index (SBF) and distant phylogenetic clades, suggesting that the ability to form biofilms is not a crucial adaptation for the S. 4,[5],12:i:- emerging success in pigs. However, using a pan-Genome-Wide Association Study (pan-GWAS) we identified genetic determinants of biofilm formation, revealing 167 common orthologous groups and genes associated with the SBF. The analysis of annotated sequences highlighted specific genetic deletions in three chromosomal regions of S. 4,[5],12:i:- correlating with SBF values: i) the complete fimbrial operon stbABCDE widely recognized as the most critical factor involved in Salmonella adherence; ii) the hxlA, hlxB, and pgiA genes, which expression in S. Typhimurium is induced in the tonsils during swine infection, and iii) the entire iroA locus related to the characteristic deletion of the second-phase flagellar genomic region in S. 4,[5],12:i:-. Consequently, we further investigated the role of the iro-genes on biofilm by constructing S. Typhimurium deletion mutants in iroBCDE and iroN. While iroBCDE showed no significant impact, iroN clearly contributed to S. Typhimurium biofilm formation. In conclusion, the pan-GWAS approach allowed us to uncover complex interactions between genetic and phenotypic factors influencing biofilm formation in S. 4,[5],12:i:- and S. Typhimurium.
摘要：
肠沙门氏菌亚种。肠鼠伤寒血清型变异4，[5]，12：i：-(所谓的S.4，[5]，12:i:-)已迅速成为欧洲人类最普遍的血清型之一，与猪肉产品食源性相关的临床病例。机制，遗传基础和生物膜的相关性，S.4，[5]，12：i：-在猪中维持和传播其存在尚不清楚。在这项研究中,我们检查了78株S.4，[5]，12：i：-（n=57）和鼠伤寒沙门氏菌（n=21），人类胃肠炎，食品和无症状猪。前者显示出较低的特异性生物膜形成指数（SBF）和遥远的系统发育进化枝，表明形成生物膜的能力不是S.4，[5]，12:i：-猪的新兴成功。然而,使用泛基因组关联研究（pan-GWAS），我们确定了生物膜形成的遗传决定因素，揭示了167个与SBF相关的常见直系同源群体和基因。对注释序列的分析突出了S.4的三个染色体区域中的特定遗传缺失，[5]，12：i：-与SBF值相关：i）被广泛认为是沙门氏菌粘附的最关键因素的完整菌毛操纵子stbABCDE；ii）hxlA，hlxB,和pgiA基因，在猪感染期间在扁桃体中诱导了鼠伤寒沙门氏菌的表达，和iii）整个iroA基因座与S中第二阶段鞭毛基因组区域的特征性缺失有关。4，[5]，12:i:-。因此,我们通过构建iroBCDE和iroN中的鼠伤寒沙门氏菌缺失突变体，进一步研究了iro基因在生物膜上的作用。虽然iroBCDE没有显着影响，iroN显然有助于鼠伤寒沙门氏菌生物膜的形成。总之,pan-GWAS方法使我们能够发现影响S中生物膜形成的遗传和表型因素之间的复杂相互作用。4，[5]，12:i:-和鼠伤寒沙门氏菌。
