An elegant means of self-protection in gram-negative bacteria by recognizing and extruding xenobiotics from the periplasmic space
An elegant means of self-protection in gram-negative bacteria by recognizing and extruding xenobiotics from the periplasmic space
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DOI：
10.1074/jbc.c200661200
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发表时间：
2003-01-24
影响因子：
4.8
通讯作者：
Nakae, T
中科院分区：
文献类型：
--
作者：
Eda, S;Maseda, H;Nakae, T
囊性纤维化患者的铜绿假单胞菌感染是导致死亡的主要原因。该菌表现出广泛的抗生素耐药性，这在很大程度上可归因于异生外排泵的表达(S)。在这里，我们展示了一种新的机制，通过这种机制，抗性-结瘤-分裂型异种生物转运蛋白可以排除潜在的危险并保护细胞内部。异源转运子MexB和MexY分别优先出口β-内酰胺类抗生素和氨基糖苷类抗生素。当MexY的两个膜外环被相应的MexB环取代时，杂合蛋白表现出对P-内酰胺的选择性(MexB型)，但不能识别氨基糖苷类。由于MexB的跨膜片段被相应的MexY跨膜片段逐一替换，所有杂合蛋白都表现出MexB类型的抗生素选择性。这些结果清楚地表明，铜绿假单胞菌中的抗性结瘤分割型外排泵通过主要突出于细胞膜上的区域来选择和运输底物。跨膜蛋白片段不太可能参与底物选择性。这些观察结果使我们提出了一种新的机制，即革兰氏阴性细菌中的异源转运蛋白在潜在的危险穿透到细胞膜之前，从周质空间选择和排出底物。
Infection of Pseudomonas aeruginosa in cystic fibrosis patients is a major cause of mortality. This organism shows wide ranging antibiotic resistance that is largely attributable to the expression of xenobiotic efflux pump(s). Here, we show a novel mechanism by which the resistance-nodulation-division-type xenobiotic transporter expels potential hazards and protects the interior of the cells. The xenobiotic transporters MexB and MexY preferentially export beta-lactam and aminoglycoside antibiotics, respectively. When two large extramembrane loops of MexY were replaced by the corresponding loops of MexB, the hybrid protein exhibited P-lactam selectivity (MexB-type), but failed to recognize aminoglycoside. As the transmembrane segment of MexB was replaced with a corresponding transmembrane segment of MexY, one-by-one for all 12 segments, all the hybrid proteins showed MexB-type antibiotic selectivity. These results clearly demonstrated that the resistance-nodulation-division-type efflux pump in P. aeruginosa selects and transports substrates via the domains that largely protrude over the cytoplasmic membrane. The transmerabrane segments were unlikely to have been involved in substrate selectivity. These observations led us to propose a novel mechanism by which the xenobiotic transporters in Gram-negative bacteria select and expel substrates from the periplasmic space before potential hazards penetrate into the cytoplasmic membrane.