Constitutive activation of PrfA tilts the balance of Listeria monocytogenes fitness towards life within the host versus environmental survival.
Constitutive activation of PrfA tilts the balance of Listeria monocytogenes fitness towards life within the host versus environmental survival.
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DOI：
10.1371/journal.pone.0015138
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发表时间：
2010-12-07
期刊：
影响因子：
3.7
通讯作者：
Freitag NE
中科院分区：
文献类型：
--
作者：
Bruno JC Jr;Freitag NE
PrfA是单核细胞增生李斯特菌致病的关键调节因子，并诱导感染宿主内多种毒力因子的表达。PrfA在细菌进入细胞质溶胶后被调节，使得蛋白质在细菌进入细胞质溶胶后被激活。触发PrfA激活的信号仍然未知，但是已经鉴定了将蛋白质锁定在高活性状态的突变（prfA* 突变）。在这份报告中，我们研究了组成性PrfA激活对L。在体外和体内的单核细胞增生适合度。而prfA* 突变体在动物感染过程中是高毒性的，突变体在肉汤培养和应激条件下的适应性受到损害。肉汤培养prfA* 相关的健身缺陷时，甘油作为主要的碳源提供缓解，在这些条件下，prfA* 突变体表现出比野生型菌株的竞争优势。甘油和其他三碳糖已被报道作为L.因此，prfA* 突变体在真核细胞内被代谢引发以用于复制。这些结果表明，迫切需要适当的环境调节PrfA活性，使L。单核细胞增生以优化宿主细胞内外的细菌适应性。
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.
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