Non-lytic protein secretion by virulence-associated Type 10 Secretion Systems in Salmonella enterica

Type 10 Secretion Systems (T10SSs) are critical virulence determinants in many bacterial pathogens and are evolutionarily derived from phage-associated lytic cassettes. In Salmonella enterica, two distinct T10SSs mediate the export of key virulence factors: typhoid toxin and cytolysin A in S. enterica serovar Typhi, the causative agent of typhoid fever, and the invasion-associated chitinase A in non-typhoidal S. enterica serovar Typhimurium, a major cause of severe salmonellosis worldwide. These systems respond to distinct environmental cues, with the typhoidal T10SS induced intracellularly within the Salmonella-containing vacuole and the non-typhoidal T10SS activated extracellularly upon contact with intestinal epithelial cells.

Here, we show that both T10SSs are tightly regulated by specific transcriptional regulators and are expressed exclusively under physiologically relevant inducing conditions. Under these conditions, T10SS activation results in robust expression of the secretion machinery at both the promoter and the protein levels. Population- and single-cell analyses further reveal that induction by environmental cues leads to activation of T10SS expression in the majority of the bacterial population in both S. Typhi and S. Typhimurium. Importantly, single-cell fluorescence and viability analyses demonstrate that secretion occurs without detectable bacterial lysis, indicating that T10SSs function as non-lytic secretion systems.

Despite their origin from phage-derived lytic modules, our data show that Salmonella T10SSs have been repurposed into actively secreting systems that export virulence factors from viable bacterial cells under tight regulatory control. Together, these findings provide new insight into the regulation and function of T10SSs in Salmonella enterica and highlight an evolutionary adaptation of phage-derived machinery into specialized secretion systems essential for bacterial virulence.