Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis
Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis
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DOI：
10.1073/pnas.1319066110
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发表时间：
2013-12-10
影响因子：
11.1
通讯作者：
Kline, Kimberly A.
中科院分区：
文献类型：
--
作者：
Kandaswamy, Kumaravel;Liew, Tze Horng;Kline, Kimberly A.
在某些革兰氏阳性菌中，毒力因子的分泌和组装发生在空间受限的病灶处。鉴于细菌中一般分泌途径的重要性和毒力因子对疾病进展的贡献，协调这些过程的病灶是有吸引力的抗菌靶标。在这项研究中，我们表明，在粪肠球菌的SecA和分选酶A，所需的附着的毒力因子的细胞壁，定位到离散域附近的隔膜或新生的隔膜网站的细菌进行通过细胞周期。我们还证明了阳离子人β-防御素与E.粪便在离散的间隔灶，这种暴露破坏了局部分泌和分类的网站。多肽抗性因子是一种通过静电排斥作用产生抗菌肽抗性的蛋白质，通过对阴离子脂质的修饰，使E。粪肠球菌对防御素的杀伤更具抗性，对阳离子抗微生物肽的靶向作用较不敏感。这些数据表明，抗微生物肽的局部靶向与其杀伤效率和破坏毒力因子组装有关。
Virulence factor secretion and assembly occurs at spatially restricted foci in some Gram-positive bacteria. Given the essentiality of the general secretion pathway in bacteria and the contribution of virulence factors to disease progression, the foci that coordinate these processes are attractive antimicrobial targets. In this study, we show in Enterococcus faecalis that SecA and Sortase A, required for the attachment of virulence factors to the cell wall, localize to discrete domains near the septum or nascent septal site as the bacteria proceed through the cell cycle. We also demonstrate that cationic human beta-defensins interact with E. faecalis at discrete septal foci, and this exposure disrupts sites of localized secretion and sorting. Modification of anionic lipids by multiple peptide resistance factor, a protein that confers antimicrobial peptide resistance by electrostatic repulsion, renders E. faecalis more resistant to killing by defensins and less susceptible to focal targeting by the cationic antimicrobial peptides. These data suggest a paradigm in which focal targeting by antimicrobial peptides is linked to their killing efficiency and to disruption of virulence factor assembly.