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首页> 外文期刊>Infection and immunity >Salmonella enterica Serovar TyphimuriumwaaP Mutants Show Increased Susceptibility to Polymyxin and Loss of Virulence In Vivo
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Salmonella enterica Serovar TyphimuriumwaaP Mutants Show Increased Susceptibility to Polymyxin and Loss of Virulence In Vivo

机译：沙门氏菌血清型鼠伤寒沙门氏菌突变体显示对多粘菌素的易感性和体内毒力的丧失

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In Escherichia coli, the waaP(rfaP) gene product was recently shown to be responsible for phosphorylation of the first heptose residue of the lipopolysaccharide (LPS) inner core region. WaaP was also shown to be necessary for the formation of a stable outer membrane. These earlier studies were performed with an avirulent rough strain of E. coli (to facilitate the structural chemistry required to properly define waaP function); therefore, we undertook the creation of a waaP mutant of Salmonella enterica serovar Typhimurium to assess the contribution of WaaP and LPS core phosphorylation to the biology of an intracellular pathogen. TheS. enterica waaP mutant described here is the first to be both genetically and structurally characterized, and its creation refutes an earlier claim that waaP mutations in S. enterica must be leaky to maintain viability. The mutant was shown to exhibit characteristics of the deep-rough phenotype, despite its ability to produce a full-length core capped with O antigen. Further, phosphoryl modifications in the LPS core region were shown to be required for resistance to polycationic antimicrobials. ThewaaP mutant was significantly more sensitive to polymyxin in both wild-type and polymyxin-resistant backgrounds, despite the decreased negative charge of the mutant LPSs. In addition, thewaaP mutation was shown to cause a complete loss of virulence in mouse infection models. Taken together, these data indicate that WaaP is a potential target for the development of novel therapeutic agents.
机译：在大肠杆菌中，最近发现 waaP （ rfaP ）基因产物负责脂多糖（LPS）的第一个庚糖残基的磷酸化）内部核心区域。还显示了WaaP对于形成稳定的外膜是必需的。这些早期研究是用无毒的E粗菌株进行的。大肠杆菌（以促进正确定义 waaP 功能所需的结构化学）;因此，我们进行了肠沙门氏菌血清型鼠伤寒沙门氏菌的 waaP 突变体的创建，以评估WaaP和LPS核心磷酸化对细胞内病原体生物学的贡献。 S。本文所述的Enterica waaP 突变体是第一个同时具有遗传和结构特征的突变体，其产生反驳了先前的说法，即 S中的 waaP 突变。 Enterica 必须泄漏以保持生存能力。尽管该突变体具有产生被O抗原封盖的全长核心的能力，但仍显示出其具有深-粗糙表型的特征。此外，显示出LPS核心区域中的磷酰基修饰对于抵抗聚阳离子抗微生物剂是必需的。尽管突变型LPS的负电荷减少，但 waaP 突变体在野生型和多粘菌抗性背景下对多粘菌素的敏感性明显更高。此外，在小鼠感染模型中， waaP 突变被证明可导致毒力完全丧失。综上所述，这些数据表明WaaP是新型治疗剂开发的潜在靶标。

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