Imipenem- and meropenem-resistant mutants of Enterobacter cloacae and Proteus rettgeri lack porins.
Imipenem- and meropenem-resistant mutants of Enterobacter cloacae and Proteus rettgeri lack porins.
复制标题
阴沟肠杆菌和雷氏变形杆菌的亚胺培南和美罗培南抗性突变体缺乏孔蛋白。
DOI：
10.1128/aac.35.6.1174
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发表时间：
1991
影响因子：
4.9
通讯作者：
Nikaido,H
中科院分区：
文献类型：
--
作者：
Raimondi,A;Traverso,A;Nikaido,H
碳青霉烯类（如亚胺培南和美罗培南）不会被常见的β-内酰胺酶快速水解。然而，通过诱变和选择，有可能分离出对美罗培南和亚胺培南高度耐药的阴沟肠杆菌和雷氏变形杆菌突变株。在E. Clostridium突变体。首先，突变菌株似乎在β-内酰胺酶的产生中被强烈地去抑制，当菌株在亚胺培南存在下生长时，β-内酰胺酶的产生达到非常高的水平。第二，这些突变体是缺乏生产的非特异性孔蛋白，判断外膜蛋白的模式，以及通过重建渗透性测定。与大多数孔蛋白缺陷突变体一样，它们的培养物是不稳定的，并且它们在不存在碳青霉烯类的情况下的培养迅速导致产生孔蛋白的回复突变体的过度生长。数据分析表明，降低的外膜渗透性和碳青霉烯类通过过量产生的酶的缓慢但显著的水解之间的协同作用可以定量地解释耐药表型，尽管目前不能排除靶点改变的可能性。对于P. rettgeri突变体，没有迹象表明β-内酰胺酶进一步去抑制，但酶水解亚胺培南比E. Cloprotein enzyme做到了。此外，在一个突变株中主要孔蛋白缺失。这些结果表明，这些肠道细菌的碳青霉烯耐药的一个主要因素是孔蛋白缺乏，这一结论形成了对比的情况下，铜绿假单胞菌，其中最普遍的一类亚胺培南耐药突变体似乎缺乏特异性通道蛋白D2，但保留了主要的非特异性孔蛋白F。
Carbapenems such as imipenem and meropenem are not rapidly hydrolyzed by commonly occurring beta-lactamases. Nevertheless, it was possible, by mutagenesis and selection, to isolate mutant strains of Enterobacter cloacae and Proteus rettgeri that are highly resistant to meropenem and imipenem. Two alterations were noted in the E. cloacae mutants. First, the mutant strains appeared to be strongly derepressed in the production of beta-lactamases, which reached a very high level when the strains were grown in the presence of imipenem. Second, these mutants were deficient in the production of nonspecific porins, as judged by the pattern of outer membrane proteins as well as by reconstitution assays of permeability. As with most porin-deficient mutants, their cultures were unstable, and their cultivation in the absence of carbapenems rapidly led to an overgrowth of porin-producing revertants. Analysis of the data suggests that the synergism between the lowered outer membrane permeability and the slow but significant hydrolysis of carbapenems by the overproduced enzymes can explain the resistance phenotypes quantitatively, although the possibility of alteration of the target cannot be excluded at present. With P. rettgeri mutants, there was no indication of further derepression of beta-lactamase, but the enzyme hydrolyzed imipenem much more efficiently than the E. cloacae enzyme did. In addition, the major porin was absent in one mutant strain. These results suggest that a major factor for the carbapenem resistance of these enteric bacteria is the porin deficiency, and this conclusion forms a contrast to the situation in Pseudomonas aeruginosa, in which the most prevalent class of imipenem-resistant mutants appears to lack the specific channel protein D2 yet retains the major nonspecific porin F.