MOLECULAR-GENETIC ANALYSIS OF A LOCUS REQUIRED FOR RESISTANCE TO ANTIMICROBIAL PEPTIDES IN SALMONELLA-TYPHIMURIUM

MOLECULAR-GENETIC ANALYSIS OF A LOCUS REQUIRED FOR RESISTANCE TO ANTIMICROBIAL PEPTIDES IN SALMONELLA-TYPHIMURIUM
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DOI:
10.1002/j.1460-2075.1993.tb06089.x
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发表时间:
1993-11-01
期刊:
影响因子:
11.4
通讯作者:
GROISMAN, EA
GROISMAN, EA
中科院分区:
生物学1区
文献类型:
--
作者:
PARRALOPEZ, C;BAER, MT;GROISMAN, EA

文献摘要

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脊椎动物和无脊椎动物对微生物感染的先天免疫部分是由具有抗菌活性的小阳离子肽介导的。成功的病原体已经进化出抵抗这些分子抗生素活性的机制。我们从鼠伤寒沙门氏菌中分离出一组基因,这些基因是对抗菌肽蜂毒肽和鱼精蛋白的毒力和耐药性所必需的。对来自赋予鱼精蛋白抗性的野生型质粒的 5.7 kb 片段进行序列分析,其中包含五个开放阅读框:sapA、sapB、sapC、sapD 和 sapF,以操纵子结构组织并转录为 5.3 kb mRNA。 SapD 和 SapF 与“ATP 结合盒”转运蛋白家族相似,包括细菌 Opp 和 SpoOK,参与寡肽的摄取;酵母 STE6,输出肽信息素所必需的;以及哺乳动物的多重耐药性,它介导癌细胞对化疗药物的耐药性。 SapA 显示出与参与肽转运的其他周质溶质结合蛋白的同一性。 SapABCDF 系统构成了肠道细菌的一种新型转运蛋白,也是第一个含有具有毒力作用的周质成分的转运蛋白。
The innate immunity of vertebrates and invertebrates to microbial infection is mediated in part by small cationic peptides with antimicrobial activity. Successful pathogens have evolved mechanisms to withstand the antibiotic activity of these molecules. We have isolated a set of genes from Salmonella typhimurium which are required for virulence and resistance to the antimicrobial peptides melittin and protamine. Sequence analysis of a 5.7 kb segment from the wild-type plasmid conferring resistance to protamine contained five open reading frames: sapA, sapB, sapC, sapD and sapF, organized in an operon structure and transcribed as a 5.3 kb mRNA. SapD and SapF exhibited similarity with the 'ATP binding cassette' family of transporters including the bacterial Opp and SpoOK, involved in the uptake of oligopeptides; the yeast STE6, necessary for the export of a peptide pheromone; and the mammalian mdr, which mediates resistance to chemotherapeutic agents in cancer cells. SapA showed identity with other periplasmic solute binding proteins involved in peptide transport. The SapABCDF system constitutes a novel transporter for enteric bacteria and the first one harboring a periplasmic component with a role in virulence.