title: A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain.
abstract: 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.
authors: The Infectious Diseases Research Laboratory, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors: Gili
authors: G
authors: Aviv
authors: Katherine
authors: K
authors: Tsyba
authors: Natalie
authors: N
authors: Steck
authors: Mali
authors: M
authors: Salmon-Divon
authors: Antje
authors: A
authors: Cornelius
authors: Galia
authors: G
authors: Rahav
authors: Guntram A
authors: GA
authors: Grassl
authors: Ohad
authors: O
authors: Gal-Mor
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D002460:Cell Line; D002645:Chickens; D027081:DNA Gyrase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007422:Intestines / Q000382:microbiology; D007557:Israel; D008628:Mercury / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009268:Nalidixic Acid / Q000494:pharmacology; D009582:Nitrofurantoin / Q000494:pharmacology; D009601:Nitroreductases / Q000235:genetics; D010641:Phenotype; D010957:Plasmids / Q000235:genetics*; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000382:microbiology; D019779:Salmonella enterica / Q000472:pathogenicity* / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D009268:Nalidixic Acid; D009582:Nitrofurantoin; D009601:Nitroreductases; D027081:DNA Gyrase; D008628:Mercury