MtrR Modulates rpoH Expression and Levels of Antimicrobial Resistance in Neisseria gonorrhoeae
MtrR Modulates rpoH Expression and Levels of Antimicrobial Resistance in Neisseria gonorrhoeae
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DOI：
10.1128/jb.01165-08
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发表时间：
2009-01-01
影响因子：
3.2
通讯作者：
Shafer, William M.
中科院分区：
文献类型：
--
作者：
Folster, Jason P.;Johnson, Paul J. T.;Shafer, William M.
已知mtrR转录调节蛋白抑制mtrCDE操纵子的转录，mtrCDE操纵子编码淋球菌拥有的多药外排泵，该泵在淋球菌抵抗某些疏水性抗生素、洗涤剂、染料和宿主衍生的抗菌剂的能力中起重要作用。为了确定mtrr是否可以对其他淋球菌基因发挥调节作用，我们进行了全基因组微阵列分析，使用从同源mtrr阳性和mtrr阴性淋球菌的活跃培养液中提取的总RNA。我们确定，至少有69个基因受到mtrr的直接或间接控制，其中47个基因受到mtrr抑制，22个基因被激活。DNA结合研究发现，编码一般应激反应σ因子RpoH(Sigma 32)的rpoH可直接被mtrR抑制，因为它与rpoH上游的DNA序列结合，该DNA序列包括rpoH启动子内的位点。MTRR也抑制了某些RpoH调节基因的表达，但这种调节可能是间接的，反映了MTRR对rpoH表达的控制。MtrR的诱导表达被发现抑制rpoH的表达，并增加淋球菌对过氧化氢(H_2O_2)和MtrC-mtrD-mtrE外排泵系统识别的抗生素(红霉素)的敏感性。我们认为，除了控制mtrCDE编码的外排泵操纵子的表达，从而控制外排泵识别的宿主抗菌素(如抗菌肽)的水平外，mtrR调节rpoH和RpoH调节基因表达水平的能力也调节了淋球菌对H_2O_2的敏感性水平。
The MtrR transcriptional-regulatory protein is known to repress transcription of the mtrCDE operon, which encodes a multidrug efflux pump possessed by Neisseria gonorrhoeae that is important in the ability of gonococci to resist certain hydrophobic antibiotics, detergents, dyes, and host-derived antimicrobials. In order to determine whether MtrR can exert regulatory action on other gonococcal genes, we performed a whole-genome microarray analysis using total RNA extracted from actively growing broth cultures of isogenic MtrR-positive and MtrR-negative gonococci. We determined that, at a minimum, 69 genes are directly or indirectly subject to MtrR control, with 47 being MtrR repressed and 22 being MtrR activated. rpoH, which encodes the general stress response sigma factor RpoH (sigma 32), was found by DNA-binding studies to be directly repressed by MtrR, as it was found to bind to a DNA sequence upstream of rpoH that included sites within the rpoH promoter. MtrR also repressed the expression of certain RpoH-regulated genes, but this regulation was likely indirect and a reflection of MtrR control of rpoH expression. Inducible expression of MtrR was found to repress rpoH expression and to increase gonococcal susceptibility to hydrogen peroxide (H2O2) and an antibiotic (erythromycin) recognized by the MtrC-MtrD-MtrE efflux pump system. We propose that, apart from its ability to control the expression of the mtrCDE-encoded efflux pump operon and, as a consequence, levels of gonococcal resistance to host antimicrobials (e. g., antimicrobial peptides) recognized by the efflux pump, the ability of MtrR to regulate the expression levels of rpoH and RpoH-regulated genes also modulates levels of gonococcal susceptibility to H2O2.