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首页> 外文期刊>Journal of bacteriology >Multidrug Efflux Pump AcrAB of Salmonella typhimuriumExcretes Only Those β-Lactam Antibiotics Containing Lipophilic Side Chains
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Multidrug Efflux Pump AcrAB of Salmonella typhimuriumExcretes Only Those β-Lactam Antibiotics Containing Lipophilic Side Chains

机译：鼠伤寒沙门氏菌的多药外排泵AcrAB仅排泄那些含有亲脂性侧链的β-内酰胺抗生素

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We found that the previously reported SS-B drug-supersusceptible mutant of Salmonella typhimurium (S. Sukupolvi, M. Vaara, I. M. Helander, P. Viljanen, and P. H. M?kel?, J. Bacteriol. 159:704–712, 1984) had a mutation in the acrAB operon. Comparison of this mutant with its parent strain and with an AcrAB-overproducing strain showed that the activity of the AcrAB efflux pump often produced significant resistance to β-lactam antibiotics in the complete absence of β-lactamase. The effect of AcrAB activity on resistance was more pronounced with agents containing more lipophilic side chains, suggesting that such compounds were better substrates for this pump. This correlation is consistent with the hypothesis that only those molecules that become at least partially partitioned into the lipid bilayer of the cytoplasmic membrane are captured by the AcrAB pump. According to this mechanism, the pump successfully excretes even those β-lactams that fail to traverse the cytoplasmic membrane, because these compounds are likely to become partitioned into the outer leaflet of the bilayer. Even the compounds with lipophilic side chains were shown to penetrate across the outer membrane relatively rapidly, if the pump was inactivated genetically or physiologically. The exclusion of such compounds, exemplified by nafcillin, from cells of the wild-type S. typhimuriumwas previously interpreted as the result of poor diffusion across the outer membrane (H. Nikaido, Biochim. Biophys. Acta 433:118–132, 1976), but it is now recognized as the consequence of efficient pumping out of entering antibiotics by the active efflux process.
机译：我们发现先前报道的SS-B药物对鼠伤寒沙门氏菌的易感突变体（S. Sukupolvi，M.Vaara，IM Helander，P.Viljanen和PH M？kel？，J.Bacteriol。 159：704–712，1984）在 acrAB 操纵子中发生了突变。将该突变体与其亲本菌株和过量生产AcrAB的菌株进行比较表明，在完全不存在β-内酰胺酶的情况下，AcrAB外排泵的活性通常产生对β-内酰胺抗生素的显着抗性。 AcrAB活性对耐药性的影响在含有更多亲脂性侧链的试剂中更为明显，这表明此类化合物是该泵的较好底物。这种相关性与以下假设一致：AcrAB泵仅捕获至少部分分隔进入细胞质膜脂质双分子层的那些分子。根据这种机制，泵甚至可以成功地排泄那些未能穿过细胞质膜的β-内酰胺，因为这些化合物很可能会被分隔成双层的外小叶。如果泵在遗传或生理上失活，即使具有亲脂性侧链的化合物也显示出相对较快地穿透外膜。从野生型 S细胞中排除以萘夫西林为例的此类化合物。鼠伤寒以前被解释为在整个外膜上扩散不良的结果（H. Nikaido，Biochim。Biophys。Acta 433：118–132，1976），但现在被认为是有效泵出的结果。通过主动外排过程进入抗生素。

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