mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides
mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides
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DOI：
10.1128/jb.184.12.3203-3213.2002
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发表时间：
2002-06-01
影响因子：
3.2
通讯作者：
Falkow, S
中科院分区：
文献类型：
--
作者：
Brodsky, IE;Ernst, RK;Falkow, S
先前证明，鼠伤寒沙门氏菌血清型的mig-14基因是胃内接种后小鼠肝脏和脾脏中细菌增殖所必需的，并且在巨噬细胞内诱导的mig-14表达受全局调节因子PhoP的控制。在这里，我们表明，米格-14启动子诱导的基本培养基中含有低镁或酸性pH值的生长，与调控PhoP一致。此外，mig-14被多粘菌素B、鱼精蛋白和哺乳动物抗微生物肽Protegrin-1强烈诱导。虽然phoP是诱导mig-14响应鱼精蛋白和保护蛋白所必需的，但mig-14仍然在phoP背景下被多粘菌素B诱导。我们还证明了mig-14是S.肠血清型鼠伤寒沙门氏菌对多粘菌素B和保护蛋白-1的敏感性。革兰氏阴性菌对多种抗菌肽的耐药性与脂多糖结构的修饰有关。然而，我们发现，mig-14是不需要这些修改之一，4-氨基阿拉伯糖添加到脂质A。此外，十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析野生型和mig-14脂多糖也显示两种菌株之间没有可检测到的差异。因此，mig-14通过一种尚未完全了解的机制导致沙门氏菌对抗菌肽产生耐药性。
It was previously demonstrated that the mig-14 gene of Salmonella enterica serovar Typhimurium is necessary for bacterial proliferation in the liver and spleen of mice following intragastric inoculation and that mig-14 expression, which is induced within macrophages, is under the control of the global regulator PhoP. Here we demonstrate that the mig-14 promoter is induced by growth in minimal medium containing low magnesium or acidic pH, consistent with regulation by PhoP. In addition, mig-14 is strongly induced by polymyxin B, protamine, and the mammalian antimicrobial peptide protegrin-1. While phoP is necessary for the induction of mig-14 in response to protamine and protegrin, mig-14 is still induced by polymyxin B in a phoP background. We also demonstrate that mig-14 is necessary for resistance of S. enterica serovar Typhimurium to both polymyxin B and protegrin-1. Gram-negative resistance to a variety of antimicrobial peptides has been correlated with modifications of lipopolysaccharide structure. However, we show that mig-14 is not required for one of these modifications, the addition of 4-aminoarabinose to lipid A. Additionally, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of wild-type and mig-14 lipopolysaccharide also shows no detectable differences between the two strains. Therefore, mig-14 contributes to Salmonella resistance to antimicrobial peptides by a mechanism that is not yet fully understood.