近日,国际著名杂志Molecular Microbiology在线刊登了德国研究人员的最新研究成果“An orphan sensor kinase controls quinolone signa production via MexT in Pseudomonas aeruginosa”,文章中,研究者揭示了铜绿假单胞菌的孤体感应激酶(orphan sensor kinase)可以通过转录调节子MexT来控制喹诺酮信号的分子水平,最终为铜绿假单胞菌的繁殖以及致病性带来帮助。
铜绿假单胞菌俗称绿脓杆菌(Pseudomonas aeruginosa,PA),是医院常见的重要机会致病菌,也是肺纤维囊肿病人慢性感染主要的致病菌,PA可以寄生在任意合适的环境中,可以感染植物、动物以及人类,而且该细菌可以通过自身基因的调节来迅速适应所繁殖的情况,这些基因在细菌的基因组占到了8.4%,涉及运动的基因、吸附的基因、营养摄取的基因、外排抗生素的基因等。PA在这些基因网络的调控下可以有效地进行繁殖并且发生各种急慢性感染。
PA可以通过N-酰基高丝氨酸内酯和2-烷基-4(1H)-喹诺酮(AQ)相关的细菌信号分子构筑自己的基因调控网络,尽管对于细菌群体感应系统调控的靶基因我们了解得很多,可是对于环境因素是如何影响群体感应系统的却知之甚少。在文章中,研究者Haussler Susanne在铜绿假单胞菌中识别了一种混合感应激酶可以通过LysR转录调节子MexT来控制AQ信号分子,包括细菌间的信号分子2-庚基-3-羟基-4(1H)-喹诺酮(该信号分子和假单胞菌喹诺酮信号分子相关,PQS),研究者的研究结果揭示了铜绿假单胞菌感应环境状况的一种新的分子机制,PA可以通过控制AQ信号分子以及自身绿脓菌素(pyocyanin)的产量来适应各种不适合的环境,PA的这种适应性对于自己处在不同环境中(包括寄生在宿主身上)进行繁殖和致病的相关基因的表达至关重要。(生物谷:T.Shen编译)
doi:10.1111/j.1365-2958.2011.07947.x
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An orphan sensor kinase controls quinolone signal production via MexT in Pseudomonas aeruginosa
Caroline Zaoui1, Jörg Overhage1, Dagmar Löns1, Ariane Zimmermann1, Mathias Müsken1,2, Piotr Bielecki2, Christian Pustelny1, Tanja Becker1, Manfred Nimtz3, Susanne Häussler1,2,*
Pseudomonas aeruginosa employs both N-acylhomoserine lactone and 2-alkyl-4(1H)-quinolone (AQ)-mediated interbacterial signalling for the orchestration of a genome-wide gene regulatory network. Despite the many advances that have been made in understanding the target genes of quorum sensing regulation, little is known on how quorum sensing systems are influenced by environmental cues. In this study, we show that AQ production is modulated by an orphan P. aeruginosa sensor kinase. Transcriptional studies of the sensor kinase (MxtR) mutant demonstrated that an induced expression of MexT, a LysR-type transcriptional regulator, largely determined the global transcriptional profile. Thereby, overexpression of the MexT-regulated MexEF-OprN efflux pump led to a delayed expression of the AQ biosynthetic genes and of AQ-dependent virulence factors. Furthermore, we demonstrated that autophosphorylation of MxtR was inhibited by ubiquinone, the central electron carrier of respiration in in vitro experiments. Our results elucidate on a mechanism by which P. aeruginosa senses environmental conditions and adapts by controlling the production of interbacterial AQ signal molecules. A regulatory function of a sensor kinase may indicate that there is a pre-emptive role of adaptation mechanisms that are turned on under distinct environmental conditions and that are important for efficient colonization and pathogenesis.