The mobilizable plasmid P3 of Salmonella enterica serovar Typhimurium SL1344 depends on the P2 plasmid for conjugative transfer into a broad range of bacteria in vitro and in vivo

The global rise of drug-resistant bacteria is of great concern. Conjugative transfer of antibiotic resistance plasmids contributes to this antibiotic resistance crisis. Despite the substantial progress in understanding the molecular basis of conjugation in vitro, the in vivo dynamics of intra- and interspecies conjugative plasmid transfer are much less understood. In this study, we focused on the streptomycin resistance-encoding mobilizable plasmid pRSF1010SL1344 (P3) of Salmonella enterica serovar Typhimurium (S. Tm) strain SL1344. We show that P3 is mobilized by interacting with the conjugation machinery of a second, conjugative plasmid pCol1B9SL1344 (P2) of SL1344. Thereby, P3 can be transferred into a broad range of relevant environmental and clinical bacterial isolates in vitro and in vivo. Our data suggests that S. Tm persisters in host tissues can serve as P3 reservoirs and foster transfer of both, P2 and P3 once they reseed the gut lumen. This adds to our understanding of resistance plasmid transfer in ecologically relevant niches including the mammalian gut.IMPORTANCES. Tm is a remarkably adaptable and globally abundant bacterial species that rapidly occupies new niches and survives unstable environmental conditions. As an enteric pathogen, it can potentially interact with a broad range of bacterial species residing in the mammalian gut. High abundance of bacteria in the gut lumen facilitate conjugation and spread of plasmid-encoded antibiotic resistance genes. By studying the transfer dynamics of the P3 plasmid in vitro and in vivo, we illustrate the impact of S. Tm-mediated antibiotic resistance spread via conjugation to a variety of relevant environmental and clinical bacterial isolates. Along with temperate phages or naked DNA, plasmids are among the most critical vehicles driving antibiotic resistance spread. Further understanding of the dynamics and drivers of antibiotic resistance transfer, along with identifying the environmental niches where this occurs, is needed to develop effective solutions for slowing down the emerging threat of multidrug-resistant bacterial pathogens.