THE 3' CONSERVED SEGMENT OF INTEGRONS CONTAINS A GENE ASSOCIATED WITH MULTIDRUG RESISTANCE TO ANTISEPTICS AND DISINFECTANTS
THE 3' CONSERVED SEGMENT OF INTEGRONS CONTAINS A GENE ASSOCIATED WITH MULTIDRUG RESISTANCE TO ANTISEPTICS AND DISINFECTANTS
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DOI：
10.1128/aac.37.4.761
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发表时间：
1993-04-01
影响因子：
4.9
通讯作者：
SKURRAY, RA
中科院分区：
文献类型：
--
作者：
PAULSEN, IT;LITTLEJOHN, TG;SKURRAY, RA
对广宿主质粒R751整合子ORF1的核苷酸序列分析发现，R751整合子ORF1的110个密码子中的前94个与其他革兰氏阴性菌整合子3'保守片段的开放阅读框ORF4相同，此后它们完全分化。ORF1和ORF4的预测产物与多药出口基因QacC具有同源性。表型分析显示，ORF1对防腐剂和消毒剂的抗性谱与qacC几乎相同，而ORF4对这些化合物的抗性水平要低得多。ORF4的产物缺乏ORF1蛋白的c端16个氨基酸，可能是由于携带sulI磺酰胺抗性决定因子的DNA片段插入而导致ORF1中断而进化而来的。因此，将ORF1命名为qacE，将其部分功能缺失的衍生物ORF4命名为qacEDELTA1。荧光实验表明，QacE特异性蛋白介导的耐药机制是质子动力激活的主动输出机制。氨基酸序列比较表明，QacE与一个具有四个跨膜片段的多药输出蛋白家族有关。
Nucleotide sequence analysis of ORF1 from the integron on the broad-host-range plasmid R751 revealed that the first 94 of 110 codons of ORF1 from R751 are identical to ORF4, an open reading frame from the 3' conserved segment of other integrons found in gram-negative bacteria, after which point they diverged completely. The predicted products of both ORF1 and ORF4 share homology with the multidrug exporter QacC. Phenotypic analysis revealed that ORF1 specifies a resistance profile to antiseptics and disinfectants almost identical to that of qacC, whereas ORF4 specifies much lower levels of resistance to these compounds. ORF4, whose product lacks the C-terminal 16 amino acids of the ORF1 protein, may have evolved by the interruption of ORF1 from the insertion of a DNA segment carrying a sulI sulfonamide resistance determinant. Hence, ORF1 was designated qacE, and its partially functional deletion derivative, ORF4, was designated qacEDELTA1. Fluorimetric experiments indicated that the mechanism of resistance mediated by QacE, the protein specified by qacE, is active export energized by proton motive force. Amino acid sequence comparisons revealed that QacE is related to a family of small multidrug export proteins with four transmembrane segments.