Adaptive evolution in asymptomatic host confers MDR Salmonella with enhanced environmental persistence and virulence

As a common cause for food-borne diseases, the Salmonella spp. are generally prevalent among livestock, whereby they are likely to be transmitted to human via environmental contamination. To explore the potential mechanism for prevalence of MDR Salmonella and its risk for dissemination via contaminated environments, we profiled the colonization dynamics of MDR Salmonella in chicken, herein we found that an adaptive evolution, driven by mutagenesis in a small protein-encoding gene (STM14_1829), conferred the multidrug resistant (MDR) Salmonella with increased fitness in asymptomatic host. Then the mechanistic study demonstrated that only one amino acid substitution in small protein STM14_1829 rendered MDR Salmonella capable to better invade and persist in phagocytotic cells by modulating bacterial flagella overexpression. Concerningly, the evolved Salmonella was also more resilient to the potential stressors generally found in environments and food processing, including heat, cold, adverse pH and oxidations. It implied that the evolved subpopulations are plausibly more persistent in environments once they contaminated through animal manure or human excreta. Moreover, the evolution promoted the pathogenesis caused by MDR Salmonella in susceptible hosts, resulting in higher risk for dissemination of pathogens via contaminated environments. Together, our data provided the novel insights into that in vivo adaptive evolution benefits Salmonella colonization, persistence and pathogenesis, by promoting bacterial tolerance via modulating flagella expression. These findings may explain the rationale behind the increasing prevalence of certain MDR Salmonella clones in livestock and associated environment, and underscoring the need for advanced strategies to tackle the possible evolution of such zoonotic pathogens.