Stationary Phase-Specific Virulence Factor Overproduction by a IasR Mutant of Pseudomonas aeruginosa
Stationary Phase-Specific Virulence Factor Overproduction by a IasR Mutant of Pseudomonas aeruginosa
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DOI：
10.1371/journal.pone.0088743
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发表时间：
2014-02-12
期刊：
影响因子：
3.7
通讯作者：
Cabeen, Matthew T.
中科院分区：
文献类型：
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作者：
Cabeen, Matthew T.
人类病原体铜绿假单胞菌分泌的毒力因子通常受群体感应控制。缺乏群体感应调节因子LasR的细胞在典型的实验室条件下表现出降低的毒力因子产生，并且在短期动物感染模型中是低毒性的，然而LasR突变体经常与囊性纤维化患者的长期感染相关。在这里，我表明，在静止期或缓慢生长的条件下，lasR细胞连续和强烈地产生重要的毒力因子绿脓菌素，而野生型细胞不。绿脓菌素过量生产的lasR细胞是允许由RsaL，一个LasR依赖性负调控阻遏损失。lasR细胞也在混合培养中贡献绿脓菌素，即使在“欺骗”条件下，它们依赖于野生型邻居的营养。最后，一些具有lasR突变的临床铜绿假单胞菌分离株可以在实验室中过量产生绿脓菌素。这些结果表明，在慢性感染中lasR细胞的缓慢生长的临床群体可能有助于通过在IasR（+）细胞不产生绿脓菌素的条件下产生毒力。
Secreted virulence factors of the human pathogen Pseudomonas aeruginosa are often under quorum sensing control. Cells lacking the quorum-sensing regulator LasR show reduced virulence factor production under typical laboratory conditions and are hypo-virulent in short-term animal infection models, yet lasR mutants are frequently associated with long-term infection in cystic fibrosis patients. Here, I show that in stationary-phase or slow-growth conditions, lasR cells continuously and strongly produce the important virulence factor pyocyanin while wild-type cells do not. Pyocyanin overproduction by lasR cells is permitted by loss of repression by RsaL, a LasR-dependent negative regulator. lasR cells also contribute pyocyanin in mixed cultures, even under "cheating'' conditions where they depend on their wild-type neighbors for nutrients. Finally, some clinical P. aeruginosa isolates with lasR mutations can overproduce pyocyanin in the laboratory. These results imply that slow-growing clinical populations of lasR cells in chronic infections may contribute to virulence by producing pyocyanin under conditions where IasR(+) cells do not.