Tian Zhe-Xian, Mac Aogáin Micheál, O'Connor Hazel F, Fargier Emilie, Mooij Marlies J, Adams Claire, Wang Yi-Ping, O'Gara Fergal
BIOMERIT Research Centre, Department of Microbiology, University College Cork, Cork, Ireland.
Microb Pathog. 2009 Oct;47(4):237-41. doi: 10.1016/j.micpath.2009.08.003. Epub 2009 Aug 13.
In the human pathogen Pseudomonas aeruginosa, the LysR-family regulator MexT modulates the induction of the tripartite MexEF-OprN resistance nodulation-division multi-drug efflux system resulting in increased resistance to diverse antibiotics. The MexEF-OprN system is normally quiescent in wild-type cells, but is highly induced in nfxC-type phenotypic mutants in a MexT dependent manner. In addition to antibiotic resistance, induction of mexEF-oprN in nfxC-type mutants has been linked to reduced levels of homoserine lactone-dependent virulence traits, including pyocyanin, elastase, rhamnolipids and PQS and to reduced expression of type three secretion effector proteins. In this study, MexT is overexpressed in wild-type PAO1 and an isogenic mexEF deletion mutant to determine if MexT regulates diverse virulence phenotypes dependent or independent of MexEF-OprN. It is shown that MexT regulates type three secretion, pyocyanin production and early surface attachment independent of MexEF-OprN. In contrast, MexT modulation of the expression of the virulence genes rhlA, lasB and hcnB is dependent on MexEF-OprN, which apparently mediates these effects via efflux of cell-signaling intermediates. The data presented demonstrates that MexT may play a more global role in modulating P. aeruginosa virulence than previously reported and suggests that MexT regulates diverse targets that mediate phenotypic alterations independent of MexEF-OprN.
在人类病原体铜绿假单胞菌中，LysR家族调节因子MexT可调节三方MexEF - OprN耐药结瘤分裂多药外排系统的诱导，从而增强对多种抗生素的耐药性。MexEF - OprN系统在野生型细胞中通常处于静止状态，但在nfxC型表型突变体中以MexT依赖的方式被高度诱导。除了抗生素耐药性外，nfxC型突变体中mexEF - oprN的诱导还与高丝氨酸内酯依赖性毒力特征水平降低有关，包括绿脓菌素、弹性蛋白酶、鼠李糖脂和PQS，以及三型分泌效应蛋白的表达降低。在本研究中，MexT在野生型PAO1和同基因的mexEF缺失突变体中过表达，以确定MexT是否调节依赖或不依赖MexEF - OprN的多种毒力表型。结果表明，MexT调节三型分泌、绿脓菌素产生和早期表面附着，且不依赖于MexEF - OprN。相反，MexT对毒力基因rhlA、lasB和hcnB表达的调节依赖于MexEF - OprN，这显然是通过细胞信号中间体的外排介导这些效应的。所呈现的数据表明，MexT在调节铜绿假单胞菌毒力方面可能比先前报道的发挥更广泛的作用，并表明MexT调节多种靶点，介导不依赖于MexEF - OprN的表型改变。
