The novel Salmonella effector STM2610 promotes epithelial cell invasion and in vivo virulence.

SALMONELLA: a major foodborne pathogen, causes gastroenteritis and life-threatening systemic infections in humans. A critical step in its pathogenesis is the invasion of intestinal epithelial cells, mediated by specialized effector proteins primarily secreted through the Salmonella Pathogenicity Island 1 (SPI-1)-encoded Type 3 Secretion System (T3SS). Although over 20 invasion-associated effectors have been identified, the full complement of these virulence determinants remains incomplete. In this study, we characterized a novel Salmonella effector, STM2610, and investigated its role in bacterial pathogenesis. β-lactamase reporter assays and Western blotting analysis showed that STM2610 is secreted into both intestinal-mimicking medium and HeLa epithelial cells, confirming its role as a effector. Notably, secretion of STM2610 was unaffected by disruption of the SPI-1 T3SS, indicating that its export occurs independently of this system. Quantitative real-time PCR (qRT-PCR) and bioluminescent reporter assays revealed that STM2610 is upregulated under intestinal-mimicking conditions and during HeLa cell invasion. Functional studies demonstrated that STM2610 mutant exhibited reduced invasion of HeLa cells and led to increased mouse survival and decreased colonization in mouse cecum, liver, and spleen. Collectively, these findings identify STM2610 as a novel SPI-1-independent effector that promotes Salmonella invasion of host epithelial cells and enhances virulence in mice, expanding the known repertoire of Salmonella effectors.