Otto Michael
Contrib Microbiol. 2009;16:136-149. doi: 10.1159/000219377. Epub 2009 Jun 2.
Antimicrobial peptides (AMPs) form a crucial part of human innate host defense, especially in neutrophil phagosomes and on epithelial surfaces. Bacteria have a variety of efficient resistance mechanisms to human AMPs, such as efflux pumps, secreted proteases, and alterations of the bacterial cell surface that are aimed to minimize attraction of the typically cationic AMPs. In addition, bacteria have specific sensors that activate AMP resistance mechanisms when AMPs are present. The prototypical Gram-negative PhoP/PhoQ and the Gram-positive Aps AMP-sensing systems were first described and investigated in Salmonella typhimurium and Staphylococcus epidermidis, respectively. Both include a classical bacterial two-component sensor/regulator system, but show many structural, mechanistic, and functional differences. The PhoP/PhoQ regulon controls a variety of genes not necessarily limited to AMP resistance mechanisms, but apparently aimed to combat innate host defense on a broad scale. In contrast, the staphylococcal Aps system predominantly upregulates AMP resistance mechanisms, namely the D-alanylation of teichoic acids, inclusion of lysyl-phosphati-dylglycerol in the cytoplasmic membrane, and expression of the putative VraFG AMP efflux pump. Notably, both systems are crucial for virulence and represent possible targets for antimicrobial therapy.
抗菌肽（AMPs）是人类固有宿主防御的关键组成部分，尤其是在中性粒细胞吞噬体和上皮表面。细菌对人类抗菌肽有多种有效的抗性机制，如外排泵、分泌的蛋白酶以及细菌细胞表面的改变，这些都是为了尽量减少典型阳离子抗菌肽的吸引力。此外，细菌有特定的传感器，当抗菌肽存在时会激活抗菌肽抗性机制。典型的革兰氏阴性菌PhoP/PhoQ和革兰氏阳性菌Aps抗菌肽传感系统分别首先在鼠伤寒沙门氏菌和表皮葡萄球菌中被描述和研究。两者都包括一个经典的细菌双组分传感器/调节系统，但在结构、机制和功能上有许多差异。PhoP/PhoQ调控子控制多种基因，不一定仅限于抗菌肽抗性机制，但其目的显然是在广泛范围内对抗固有宿主防御。相比之下，葡萄球菌Aps系统主要上调抗菌肽抗性机制，即磷壁酸的D-丙氨酰化、细胞质膜中赖氨酸磷脂酰甘油的掺入以及假定的VraFG抗菌肽外排泵的表达。值得注意的是，这两个系统对毒力都至关重要，并且是抗菌治疗的可能靶点。
