Natural Mutation of PrfA K10N/T151A Enhances Serotype 4h Listeria monocytogenes Virulence

PrfA is a key virulence regulator for Listeria monocytogenes (Lm) responding to host environment. Here we report that the natural mutation in PrfA_K10N/T151A enhanced the pathogenicity of hypervirulent serotype 4h L. monocytogenes. We characterized the phylogenetic tree of PrfA, and found that PrfA_K10N/T151A prevalently distributed in all serotype 4h isolates. Remarkably, the growth rate of serotype 4h strain Lm XYSN was significantly slower than EGD-e, in contrast, the substitution mutant Lm PrfA_N10K/A151T increased the growth rate of L. monocytogenes. Notably, PrfA_K10N/T151A upregulated the expression of multiple virulent genes of Lm XYSN cultured in brain-heart infusion medium, and increased the invasion ability in HeLa and Caco-2 cells. Importantly, the PrfA_K10N/T151A mutation significantly enhanced the colonization and survival of Lm XYSN in vivo. Therefore, our findings indicate that the natural mutation of PrfA_K10N/T151A enhances the PrfA activity, resulting in the upregulation of various virulence genes and contributing to virulence and pathogenesis of Lm XYSN, which contributes to the hypervirulence of serotype 4h isolates.