A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain

Summary Of all known S almonella 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 I srael, 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 I srael 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.