Crouch Marie-Laure, Becker Lynne A, Bang Iel-Soo, Tanabe Hiroki, Ouellette Andre J, Fang Ferric C
Department of Laboratory Medicine, Universit of Washington School of Medicine, Seattle, WA 98195, USA.
Mol Microbiol. 2005 May;56(3):789-99. doi: 10.1111/j.1365-2958.2005.04578.x.
The enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters a variety of anti-microbial peptides during the course of infection. We report here that the extracytoplasmic sigma factor sigma(E) (RpoE) is required for Salmonella resistance to killing by the bactericidal/permeability-increasing protein (BPI)-derived peptide P2 and the murine alpha-defensin cryptdin-4 (Crp4). Moreover, sigma(E)-deficient S. Typhimurium is attenuated for virulence after oral infection of immunocompromised gp91phox(-/-) mice that lack a functional NADPH phagocyte oxidase, suggesting that sigma(E) plays an important role in resistance to non-oxidative mucosal host defences such as anti-microbial peptides. Although both P2 and Crp4 target the cell envelope, bacterial killing by these peptides appears to occur by distinct mechanisms. Formate enhances bacterial resistance to P2, as previously demonstrated, but not to Crp4. Both sigma(E) and cytoplasmic membrane-associated formate dehydrogenase are required for the protective effect of formate against P2. In contrast to P2, Crp4 does not inhibit bacterial respiration at lethal concentrations. However, both peptides induce expression of rpoE, suggesting that they trigger a common mechanism for sensing extracytoplasmic stress.
肠道病原体鼠伤寒沙门氏菌（Salmonella enterica serovar Typhimurium，简称鼠伤寒沙门氏菌）在感染过程中会遇到多种抗菌肽。我们在此报告，胞外西格玛因子西格玛E（RpoE）是鼠伤寒沙门氏菌抵抗杀菌/通透性增加蛋白（BPI）衍生肽P2和小鼠α-防御素隐窝素-4（Crp4）杀伤所必需的。此外，缺乏西格玛E的鼠伤寒沙门氏菌在口服感染缺乏功能性NADPH吞噬细胞氧化酶的免疫受损gp91phox（-/-）小鼠后毒力减弱，这表明西格玛E在抵抗非氧化性黏膜宿主防御（如抗菌肽）中起重要作用。尽管P2和Crp4都靶向细胞膜，但这些肽对细菌的杀伤似乎通过不同机制发生。如先前所示，甲酸盐可增强细菌对P2的抗性，但对Crp4无效。甲酸盐对P2的保护作用既需要西格玛E也需要与细胞质膜相关的甲酸脱氢酶。与P2不同，致死浓度的Crp4不会抑制细菌呼吸。然而，这两种肽都会诱导rpoE的表达，表明它们触发了一种感知胞外应激的共同机制。
