PHOP-REG SALMONELLA RESISTANCE TO ANTIMICR PEPTIDES MAGAININ 2 AND POLYMYXIN B

PHOP-REG 沙门氏菌对抗微生物肽 MAGAININ 2 和多粘菌素 B 的抗性

• 批准号: 7355243
• 负责人: Yixin Shi
• 金额: $ 0.59万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355243
• 关键词: PHOP; REG; SALMONELLA; RESISTANCE; ANTIMICR

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In Salmonella enterica, the PhoP PhoQ two-component system governs resistance to structurally different antimicrobial peptides including the alpha-helical magainin 2, the -sheet defensins and the cyclic lipopeptide polymyxin B. To identify the PhoP-regulated determinants mediating peptide resistance, we prepared a plasmid library from a phoP mutant, introduced it into a phoP mutant and selected for magainin-resistant clones. One of the clones harboured the PhoP-activated ugtL gene, deletion of which rendered Salmonella susceptible to magainin 2 and polymyxin B, but not defensin HNP-1. We established that ugtL encodes an inner membrane protein that promotes the formation of monophosphorylated lipid A in the lipopolysaccharide. Inactivation of both ugtL and the regulatory gene pmrA, which controls lipid A modifications required for resistance to polymxyin B (but not to magainin 2) and is post-transcriptionally activated by the PhoP PhoQ system, resulted in a strain that was as susceptible to polymyxin B as a phoP mutant. The most frequently recovered clone harboured the yqjA gene, which we show is PhoP regulated and required for resistance to magainin 2 but not to polymyxin B or defensin HNP-1. Our results indicate that different PhoP-mediated modifications in lipid A are necessary for resistance to different antimicrobial peptides.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在肠道沙门氏菌中，PhoP PhoQ双组分系统控制对结构上不同的抗菌肽的抗性，包括α-螺旋爪蟾抗菌肽2、β-折叠防御素和环状脂肽多粘菌素B。为了鉴定PhoP调节的决定簇介导的肽抗性，我们从phoP突变体制备了质粒文库，将其引入phoP突变体并选择爪蟾抗菌肽抗性克隆。其中一个克隆含有PhoP激活的ugtL基因，该基因的缺失使沙门氏菌对爪蟾抗菌肽2和多粘菌素B敏感，但对防御素HNP-1不敏感。我们确定ugtL编码一种内膜蛋白，该蛋白促进脂多糖中单磷酸化脂质A的形成。ugtL和调控基因pmrA的失活导致菌株对多粘菌素B（但不对爪蟾抗菌肽2）的抗性所需的脂质A修饰，并由PhoP PhoQ系统转录后激活，该菌株对多粘菌素B和phoP突变体一样敏感。最常见的回收克隆窝藏yqjA基因，我们表明是PhoP调节和所需的抗性magainin 2，但不多粘菌素B或防御素HNP-1。我们的研究结果表明，不同的PhoP介导的脂质A的修饰是必要的耐药不同的抗菌肽。