The Pseudomonas aeruginosa reference strain PA14 displays increased virulence due to a mutation in ladS.
The Pseudomonas aeruginosa reference strain PA14 displays increased virulence due to a mutation in ladS.
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DOI：
10.1371/journal.pone.0029113
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Filloux A
中科院分区：
文献类型：
--
作者：
Mikkelsen H;McMullan R;Filloux A
铜绿假单胞菌是一种可引起多种宿主急性和慢性感染的病原体。铜绿假单胞菌的致病潜力是菌株依赖性的。PA 14是一种高毒力菌株，在广泛的生物体中引起疾病，而PAO 1是中等毒力的。尽管PA 14携带PAO 1中不存在的致病岛，但特定基因簇的存在或不存在并不能预测毒力。在这里，我们表明，强毒株PA 14有一个获得性突变的ladS基因。该突变对生物膜具有有害影响，同时其导致升高的III型分泌系统（T3 SS）活性和增加的对哺乳动物细胞的细胞毒性。这些表型可以通过修复PA 14基因组上的ladS突变来逆转。RetS/LadS/GacS信号级联与毒力以及急性和慢性感染之间的转换相关。RetS是下调生物膜形成并上调T3 SS的传感器。retS的突变在从慢性感染的囊性纤维化患者分离的菌株中获得，并导致超生物膜形成和细胞毒性降低。相反，LadS传感器促进生物膜形成并抑制T3 SS。我们的结论是，LADS突变是部分负责PA 14的高细胞毒性，我们的研究结果证实了RetS和LADS在急性和慢性感染之间的转换的核心作用。考虑到参考菌株PA 14在感染和毒力模型中的广泛使用，在未来的研究中，ladS突变对观察到的表型造成的偏倚将是至关重要的。
Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 carries pathogenicity islands that are absent in PAO1, the presence or absence of specific gene clusters is not predictive of virulence. Here, we show that the virulent strain PA14 has an acquired mutation in the ladS gene. This mutation has a deleterious impact on biofilm, while it results in elevated type III secretion system (T3SS) activity and increased cytotoxicity towards mammalian cells. These phenotypes can be reverted by repairing the ladS mutation on the PA14 genome. The RetS/LadS/GacS signaling cascade is associated with virulence and the switch between acute and chronic infections. RetS is a sensor that down-regulates biofilm formation and up-regulates the T3SS. Mutations in retS are acquired in strains isolated from chronically infected cystic fibrosis patients and lead to hyperbiofilm formation and reduced cytotoxicity. Conversely, the LadS sensor promotes biofilm formation and represses the T3SS. We conclude that the ladS mutation is partly responsible for the high cytotoxicity of PA14, and our findings corroborate the central role of RetS and LadS in the switch between acute and chronic infections. Given the extensive use of the reference strain PA14 in infection and virulence models, the bias caused by the ladS mutation on the observed phenotypes will be crucial to consider in future research.
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影响因子：
3.2
作者：
Chand, Nikhilesh S.;Lee, Jenny See-Wai;Hung, Deborah T.
通讯作者：
Hung, Deborah T.
DOI：
10.1073/pnas.0437901100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Coleman, FT;Mueschenborn, S;Pier, GB
通讯作者：
Pier, GB
影响因子：
6.4
作者：
Hoboth, Christina;Hoffmann, Reinhard;Hogardt, Michael
通讯作者：
Hogardt, Michael
基因组分析表明，铜绿假单胞菌的毒力是组合。
影响因子：
12.3
作者：
Lee DG;Urbach JM;Wu G;Liberati NT;Feinbaum RL;Miyata S;Diggins LT;He J;Saucier M;Déziel E;Friedman L;Li L;Grills G;Montgomery K;Kucherlapati R;Rahme LG;Ausubel FM
通讯作者：
Ausubel FM
影响因子：
3.1
作者：
Lee, VT;Smith, RS;Lory, S
通讯作者：
Lory, S