Samples were taken from mice co-housed mice that were infected with Salmonella Typhimurium then treated with ceftriaxone. 16S analysis of microbial composition shows ablation of gut microbiota after antibiotic treatment, then transfer of Salmonella between animals. In experiments where mice are left untreated, transfer of micriobiota between co-housed animals restores colonisation resistance and prevents Salmonella transmission.

The formation of antibiotic-recalcitrant reservoirs contributes to clearance failure and relapse of bacterial infections in vivo. Salmonella Typhimurium survives antibiotic exposure in host tissues and systemic sites, and can later resume replication and migrate into the gut, which facilitates transmission to new hosts. It is not well understood how relapsing infection is shaped by Salmonella virulence factors, nor how antibiotic therapy affects transmission from infected animals to new hosts. Here, we used a long-term murine model of systemic infection to study the recovery and transmission of persisters following antibiotic treatment. Virulence factors supporting intracellular replication were not required for antibiotic recalcitrance, but contributed to bacterial regrowth in systemic niches which resumed in the days following treatment, resulting in a significant increase in bacterial abundance over time. After withdrawal of antibiotics, we observed robust gut colonisation that was initiated by rare gut-seeding events, as indicated by DNA barcoding. Clonal transmission and invasive infection was observed in co-housed animals that also received antibiotic treatment. However, bacterial migration to the gut and transmission to uninfected hosts was blocked when animals were co-housed with naïve cagemates, suggesting that healthy untreated animals can confer community colonisation resistance that protects against relapsing persisters. Collectively, we describe how antibiotics impose a trade-off situation in which alleviation of colonisation resistance is exploited by recalcitrant bacteria that survived antibiotic treatment, permitting opportunities for gut colonisation and transmission to new hosts. These data provide new insights into how antibiotic recalcitrant tissue reservoirs are shaped by pathogen-host-microbiota dynamics, and provide a rationale for preventing bacterial transmission via maintenance of community colonisation resistance.