Farrow John M, Pesci Everett C
Department of Microbiology and Immunology, The Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC, 27834, USA.
Mol Microbiol. 2017 Apr;104(1):78-91. doi: 10.1111/mmi.13611. Epub 2017 Jan 26.
The ubiquitous bacterium Pseudomonas aeruginosa is an opportunistic pathogen that can cause serious infections in immunocompromised individuals. P. aeruginosa virulence is controlled partly by intercellular communication, and the transcription factor PqsR is a necessary component in the P. aeruginosa cell-to-cell signaling network. PqsR acts as the receptor for the Pseudomonas quinolone signal, and it controls the production of 2-alkyl-4-quinolone molecules which are important for pathogenicity. Previous studies showed that the expression of pqsR is positively controlled by the quorum-sensing regulator LasR, but it was unclear how LasR is able to induce pqsR transcription. In this report, we further investigated the control of pqsR, and discovered two separate promoter sites that contribute to pqsR expression. LasR-mediated activation occurs at the distal promoter site, but this activation can be antagonized by the regulator CysB. The proximal promoter site also contributes to pqsR transcription, but initiation at this site is inhibited by a negative regulatory sequence element, and potentially by the H-NS family members MvaT and MvaU. We propose a model where positive and negative regulatory influences at each promoter site are integrated to modify pqsR expression. This arrangement could allow for information from both environmental signals and cell-to-cell communication to influence PqsR levels.
无处不在的细菌铜绿假单胞菌是一种机会致病菌,可在免疫功能低下的个体中引起严重感染。铜绿假单胞菌的毒力部分受细胞间通讯控制,转录因子PqsR是铜绿假单胞菌细胞间信号网络的必要组成部分。PqsR作为假单胞菌喹诺酮信号的受体,控制对致病性很重要的2-烷基-4-喹诺酮分子的产生。先前的研究表明,pqsR的表达受群体感应调节因子LasR的正向调控,但尚不清楚LasR如何诱导pqsR转录。在本报告中,我们进一步研究了pqsR的调控,发现了两个独立的启动子位点,它们有助于pqsR的表达。LasR介导的激活发生在远端启动子位点,但这种激活可被调节因子CysB拮抗。近端启动子位点也有助于pqsR转录,但该位点的起始受负调控序列元件以及可能受H-NS家族成员MvaT和MvaU的抑制。我们提出了一个模型,其中每个启动子位点的正向和负向调控影响被整合以调节pqsR的表达。这种安排可以使来自环境信号和细胞间通讯的信息都影响PqsR的水平。