Fis suppresses late-stage virulence gene expression in Yersinia pseudotuberculosis at environmental temperatures

In Yersinia pseudotuberculosis, Fis plays a critical, yet poorly understood role in virulence. Here, we present a comparative transcriptomic analysis of Y. pseudotuberculosis wild type and fis deletion mutant at environmental (25°C) and host-relevant (37°C) temperatures.

Our data show that Fis modulates the expression of more than 600 genes across 16 functional categories. Notably, Fis exerts reciprocal, temperature-dependent control over virulence genes, including those encoding the type III secretion system (T3SS) and Yersinia effector proteins (Yops), flagella biosynthesis, and cell adherence/invasion factors. Functional assays revealed that fis deletion disrupts this regulatory balance, producing a host-defense-like state at 25°C characterized by complete loss of motility, upregulation of the virulence master regulator LcrF, aberrant Yop secretion, impaired phagocytosis by host cells, and increased pathogenicity in the Galleria mellonella infection model.