ADAPTATION OF THE SALMONELLA INFANTIS RESISTANCE-VIRULENCE PLASMID (PESI) FOR HORIZONTAL TRANSFER IN THE INTESTINE OF WARM-BLOODED HOSTS

Salmonella enterica serovar Infantis is one of the most commonly isolated salmonellae worldwide. Recently, we showed that the emergence of S. Infantis in Israel was facilitaded by horizontal acquisition of a unique megaplasmid (pESI) confereing hyper-resistance and virulence phenotypes. Here we elucidate the evolutionary history of pESI and its fixation in the local S. infantis population. Furthermore, we show that pESI conjugation is repressed at the ambient temperature (27°C), under aerobic conditions and by bile. In contrast, pESI mobilization and the transcription of the conjugation system genes are specifically induced under 37-41°C, moderate osmolarity and microaerobic conditions, characterizing the intestinal environment of warm-blooded animals. Using the mouse model, we show that following S. Infantis infection, pESI is horizontally transferred to various microbiota species, including distantly-related Gram-positive bacteria. A curious over- representation of pESI-transfer was found into Lactobacillus spp., possibly due to their reactive oxygen species secretion, found to further induce pESI conjugation. These findings demonstrate the adaptation of a selfish clinically-relevant megaplasmid for transmission in the gut of warm-blooded animals and its surprising capability to disseminate to the host microbiota. Furthermore, the data highlight the role of the microbiome in the spread of resistance and virulence genes, among commensals and pathogens.