Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction
Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction
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DOI：
10.1128/jb.187.15.5341-5346.2005
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发表时间：
2005-08-01
影响因子：
3.2
通讯作者：
Plésiat, P
中科院分区：
文献类型：
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作者：
Jeannot, K;Sobel, ML;Plésiat, P
MexXY是一种可诱导的外排系统，有助于铜绿假单胞菌对抗生素的天然耐药性。在参考菌株PAO 1中逆转录后涉及实时PCR的实验显示，各种核糖体抑制剂（例如，氯霉素、四环素、大环内酯类和氨基糖苷类），但不被作用于其它细胞靶点的抗生素（例如，β-内酰胺类、氟喹诺酮类）。阐明了外排系统和翻译机器之间的功能联系，核糖体保护质粒编码的蛋白TetO和ErmBP增加了PAO 1的Delta mexAB-oprM突变体对四环素和红霉素的抗性，以及诱导mexY所需的两种药物的浓度。此外，自发突变导致对双氢链霉素或壮观霉素的特异性抗性，也提高了菌株PAO 1中mexXY诱导的最低药物浓度。虽然在基因mexZ（其编码操纵子mexXY的推定阻遏物）缺陷的PAO 1突变体中强烈上调，但基因mexY仍可被诸如四环素、氯霉素和壮观霉素的试剂诱导，这表明mexXY的另外的调控位点。总而言之，这些数据表明MexXY和核糖体之间的生理相互作用，并提示MexXY除了抗生素外排之外的另一种功能。
MexXY is an inducible efflux system that contributes to the natural resistance of Pseudomonas aeruginosa to antibiotics. Experiments involving real-time PCR after reverse transcription in reference strain PAO1 showed concentration-dependent induction of gene mexY by various ribosome inhibitors (e.g., chloramphenicol, tetracycline, macrolides, and aminoglycosides) but not by antibiotics acting on other cellular targets (e.g., beta-lactams, fluoroquinolones). Confirming a functional link between the efflux system and the translational machinery, ribosome protection by plasmid-encoded proteins TetO and ErmBP increased the resistance of a Delta mexAB-oprM mutant of PAO1 to tetracycline and erythromycin, respectively, as well as the concentrations of both drugs required to induce mexY. Furthermore, spontaneous mutations resulting in specific resistance to dihydrostreptomycin or spectinomycin also raised the minimal drug concentration for mexXY induction in strain PAO1. While strongly upregulated in a PAO1 mutant defective in gene mexZ (which codes for a putative repressor of operon mexXY, gene mexY remained inducible by agents such as tetracycline, chloramphenicol, and spectinomycin, suggesting additional regulatory loci for mexXY. Altogether, these data demonstrate physiological interplays between MexXY and the ribosome and are suggestive of an alternative function for MexXY beyond antibiotic efflux.