ROLE OF MEXA-MEXB-OPRM IN ANTIBIOTIC EFFLUX IN PSEUDOMONAS-AERUGINOSA
ROLE OF MEXA-MEXB-OPRM IN ANTIBIOTIC EFFLUX IN PSEUDOMONAS-AERUGINOSA
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DOI：
10.1128/aac.39.9.1948
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发表时间：
1995-09-01
影响因子：
4.9
通讯作者：
POOLE, K
中科院分区：
文献类型：
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作者：
LI, XZ;NIKAIDO, H;POOLE, K
我们之前描述了mexA-mexB-oprK，一种参与铜绿假单胞菌中绿脓菌荧光素输出的操纵子，并提出这些基因的产物也有助于几种抗生素的主动外排（K. Poole，K.克雷贝斯角McNally和S. Neshat，J. Bacteriol. 175：7363-7372，1993）。最近，该外排系统的外膜组分被证明是OprM，而不是OprK（N. Gotoh和K. Poole，未发表的结果）。在本研究中，通过测量完整细胞中的药物蓄积，证实并扩展了关于该系统外排活性的结论。因此，四环素和诺氟沙星的稳态积累水平增加mexA和oprM mil突变体。mexA和oprM无效突变体也显示出对多种β-内酰胺抗生素的敏感性增加和苄青霉素稳态积累水平的增加，表明MexA-MexB-OprM泵也流出β-内酰胺。此外，用质子导体对细胞质膜进行去质子化总是产生积累水平的强烈增加。最后，一个单步突变体过量生产MexAB-OprM积累四环素和氯霉素比亲本菌株更少，更耐多种抗菌化合物，包括β-内酰胺。这些结果支持这些蛋白质通过多药主动外排过程促成铜绿假单胞菌的内在耐药性的观点。
We have earlier described mexA-mexB-oprK, an operon involved in pyoverdine export in Pseudomonas aeruginosa, and suggested that the products of these genes also contribute to the active efflux of several antibiotics (K. Poole, K. Krebes, C. McNally, and S. Neshat, J. Bacteriol. 175:7363-7372, 1993), Recently the outer membrane component of this efflux system was shown to be OprM, rather than OprK (N. Gotoh and K. Poole, unpublished results). In the present study, the conclusion concerning the efflux activity of this system was confirmed and extended by the measurement of drug accumulation in intact cells. Thus, the steady-state accumulation levels of tetracycline and norfloxacin were increased in mexA and oprM mil mutants. mexA and oprM null mutants also showed an increase in susceptibility to a wide variety of beta-lactam antibiotics and an increase in the steady-state accumulation level of benzylpenicillin, indicating that the MexA-MexB-OprM pump also effluxes beta-lactams. Furthermore, deenergization of the cytoplasmic membrane with a proton conductor always produced a strong increase in the accumulation level. Finally, a single-step mutant overproducing MexAB-OprM accumulated less tetracycline and chloramphenicol than the parent strain and was more resistant to a wide range of antimicrobial compounds, including beta-lactams. These results support the notion that these proteins contribute to the intrinsic resistance of P. aeruginosa through the multidrug active efflux process.