Department of Global Health, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2010 Dec 7;5(12):e15138. doi: 10.1371/journal.pone.0015138.
PrfA is a key regulator of Listeria monocytogenes pathogenesis and induces the expression of multiple virulence factors within the infected host. PrfA is post-translationally regulated such that the protein becomes activated upon bacterial entry into the cell cytosol. The signal that triggers PrfA activation remains unknown, however mutations have been identified (prfA* mutations) that lock the protein into a high activity state. In this report we examine the consequences of constitutive PrfA activation on L. monocytogenes fitness both in vitro and in vivo. Whereas prfA* mutants were hyper-virulent during animal infection, the mutants were compromised for fitness in broth culture and under conditions of stress. Broth culture prfA*-associated fitness defects were alleviated when glycerol was provided as the principal carbon source; under these conditions prfA* mutants exhibited a competitive advantage over wild type strains. Glycerol and other three carbon sugars have been reported to serve as primary carbon sources for L. monocytogenes during cytosolic growth, thus prfA* mutants are metabolically-primed for replication within eukaryotic cells. These results indicate the critical need for environment-appropriate regulation of PrfA activity to enable L. monocytogenes to optimize bacterial fitness inside and outside of host cells.
PrfA 是李斯特菌属致病的关键调节因子，可在感染宿主中诱导多种毒力因子的表达。PrfA 受到翻译后调控，使得该蛋白在细菌进入细胞胞质后被激活。然而，触发 PrfA 激活的信号仍然未知，尽管已经鉴定出了将蛋白锁定在高活性状态的突变（prfA突变）。在本报告中，我们研究了持续激活 PrfA 对李斯特菌属在体外和体内适应性的影响。虽然 prfA突变体在动物感染期间具有超毒力，但在肉汤培养和应激条件下，突变体的适应性受损。当甘油作为主要碳源提供时，可缓解 PrfA 相关的肉汤培养适应性缺陷；在这些条件下，prfA突变体相对于野生型菌株具有竞争优势。甘油和其他三种碳糖已被报道在李斯特菌属的胞质生长中作为主要碳源，因此，prfA突变体在真核细胞内复制时具有代谢优势。这些结果表明，需要对 PrfA 活性进行适当的环境调节，以使李斯特菌属能够优化细胞内外的细菌适应性。
