Salmonella enterica subsp. enterica serovar Infantis str. 119944 Genome sequencing and assembly. Salmonella enterica subsp. enterica serovar Infantis str. 119944

Salmonella enterica is a human and animal pathogen, posing a major threat to public health. Of all known S. enterica serovars, S. Infantis is one of the most commonly isolated and has been recently emerging worldwide. Herein, we report comparative analyses between pre-emerging and recently emerged, local S. Infantis populations. We show that the highly clonal emerging population is characterized by a lateral acquisition of a ~280 kb previously uncharacterized virulence plasmid accompanied by adaptive point mutations in the DNA gyrase (gyrA) and nitroreductase (nfsA) genes, conferring resistance to quinolones and nitrofurans, respectively. The acquired plasmid (designated pSI119944), evolved through recombination and multiple insertion events of mobile genetic elements, provides further resistance to tetracycline (terRA), sulfamethoxazol (sulI) and trimethoprim (dfrA), but also increases bacterial tolerance to inorganic mercury (mer operon) and hydrogen peroxide. Furthermore, pSI119944 carries the yersiniabactin siderophore system and two novel chaperon-usher fimbriae. In-vitro studies showed that the emerging strain presents eminent virulence-associated phenotypes including elevated biofilm formation, adhesion and invasion to avian and mammalian host cells in a pSI119944-dependent manner. In-vivo mouse infections demonstrated higher pathogenicity and increased intestinal inflammation caused by the emerging strain compared to a plasmidless pre-emerging strain. Our results indicate that pSI119944 acquisition and adaptive chromosomal mutations facilitated the emergence of a fitter and more virulent strain that replaced the local S. Infantis community in an exceptionally short time of 2-3 years. We believe that these findings demonstrate a universal paradigm and reveal general microevolution machinery relevant to the emergence of other bacterial pathogens.