The second type VI secretion system of Pseudomonas aeruginosa strain PAO1 is regulated by quorum sensing and Fur and modulates internalization in epithelial cells.
The second type VI secretion system of Pseudomonas aeruginosa strain PAO1 is regulated by quorum sensing and Fur and modulates internalization in epithelial cells.
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DOI：
10.1074/jbc.m112.376368
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发表时间：
2012-08-03
期刊：
影响因子：
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通讯作者：
Bleves S
中科院分区：
文献类型：
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作者：
Sana TG;Hachani A;Bucior I;Soscia C;Garvis S;Termine E;Engel J;Filloux A;Bleves S
背景：铜绿假单胞菌中存在三种T6 SS。H1-T6 SS分泌溶菌毒素。结果：H2-T6 SS受群体感应和Fur的调节，并通过PI 3 K-Akt宿主通路的激活调节上皮细胞的内化。结论：H2-T6 SS在致病性中起一定作用。意义：与抗原核H1-T6 SS相反，H2-T6 SS靶向人细胞。这些T6 SS可以执行在建立感染中重要的不同功能。铜绿假单胞菌PAO 1的基因组包含三种VI型分泌系统（T6 SS），称为H1-、H2-和H3-T6 SS。H1-T6 SS分泌三种鉴定的毒素，靶向其他细菌，为铜绿假单胞菌提供适应性优势，并可能有助于慢性感染中的细菌发病机制。然而，没有具体的基板或定义的角色已被描述为其他两个系统。在这里，我们证明了菌株PAO 1的H2-T6 SS基因的表达是上调的过渡期间，从指数到稳定期的增长和调节的Las和Rhl群体感应系统。此外，我们确定了两个推定的Fur盒的启动子区域，并发现H2-T6 SS转录负调控铁。我们还表明，H2-T6 SS系统增强了细菌摄取到HeLa细胞（75%的减少与H2-T6 SS突变体的内化），并通过磷脂酰肌醇3-激酶依赖性途径，诱导Akt激活宿主细胞（Akt磷酸化减少50%）到肺上皮细胞。最后，我们表明H2-T6 SS在蠕虫模型中的铜绿假单胞菌毒力中起作用。因此，与H1-T6 SS相反，H2-T6 SS调节与真核宿主细胞的相互作用。总之，T6 SS可以执行不同的功能，这些功能在人类宿主中建立慢性铜绿假单胞菌感染中可能是重要的。
Background: Three T6SSs are present in P. aeruginosa. H1-T6SS secretes bacteriolytic toxins. Results: H2-T6SS is regulated by quorum sensing and Fur and modulates internalization in epithelial cells through PI3K-Akt host pathway activation. Conclusion: H2-T6SS plays a role in virulence. Significance: In contrast to the anti-prokaryotic H1-T6SS, H2-T6SS targets human cells. Those T6SSs can carry out different functions important in establishing infection. The genome of Pseudomonas aeruginosa PAO1 contains three type VI secretion systems (T6SSs) called H1-, H2-, and H3-T6SS. The H1-T6SS secretes three identified toxins that target other bacteria, providing a fitness advantage for P. aeruginosa, and likely contributes to bacterial pathogenesis in chronic infections. However, no specific substrates or defined roles have been described for the two other systems. Here, we demonstrate that the expression of H2-T6SS genes of strain PAO1 is up-regulated during the transition from exponential to stationary phase growth and regulated by the Las and Rhl quorum sensing systems. In addition, we identify two putative Fur boxes in the promoter region and find that H2-T6SS transcription is negatively regulated by iron. We also show that the H2-T6SS system enhances bacterial uptake into HeLa cells (75% decrease in internalization with a H2-T6SS mutant) and into lung epithelial cells through a phosphatidylinositol 3-kinase-dependent pathway that induces Akt activation in the host cell (50% decrease in Akt phosphorylation). Finally, we show that H2-T6SS plays a role in P. aeruginosa virulence in the worm model. Thus, in contrast to H1-T6SS, H2-T6SS modulates interaction with eukaryotic host cells. Together, T6SS can carry out different functions that may be important in establishing chronic P. aeruginosa infections in the human host.