Unveiling the dance of evolution: Pla-mediated cleavage of Ymt modulates the virulence dynamics of Yersinia pestis

作者：Gengshan Wu, Yazhou Zhou, Shiyang Cao, Yarong Wu, Tong Wang, Yu Zhang, Xiaoyi Wang, Yajun Song, Ruifu Yang, Zongmin Du · 发表于：mBio · 年份：2024 · DOI：10.1128/mbio.01075-24 · 被引用次数：3 · 研究领域：Yersinia bacterium, plague, ectoparasites research、Vector-borne infectious diseases、Bacillus and Francisella bacterial research

ABSTRACT Yersinia pestis has recently evolved into a highly lethal flea-borne pathogen through the pseudogenization of extensive genes and the acquisition of exogenous plasmids. Particularly noteworthy are the newly acquired pPCP1 and pMT1 plasmids, which encode the virulence determinants Pla and Yersinia murine toxin (Ymt), crucial for subcutaneous infection and survival within flea vector of Y. pestis , respectively. This study reveals that Pla can cleave Ymt at K299 both in vivo and in vitro. Y. pestis expressing Ymt K299A displays enhanced in vitro biofilm formation and increased blood survival, indicating significant roles of Pla-mediated Ymt cleavage in these phenotypes. Intriguingly, although both the ancestral form of Pla and the prevalent Pla-I259T variant in modern Y. pestis strains are capable of cleaving Ymt at K299, the cleavage efficiency of Pla-I259T is only half that of the ancestral variant. In subcutaneous infection, mice infected with Δ ymt::ymt- K299A show significantly prolonged survival compared to those infected with Δ ymt::ymt . Similarly, infection with Δ pla::pla- I259T also results in extended survival compared to Δ pla::pla infection. These data demonstrate that the I259T substitution of Pla mitigates the enhanced virulence of Y. pestis in mice caused by Pla-mediated Ymt cleavage, thereby prolonging the survival period of infected animals and potentially conferring advantages on the transmission of Y. pestis to the next host. These findings deepen ...