Bomberger Jennifer M, Maceachran Daniel P, Coutermarsh Bonita A, Ye Siying, O'Toole George A, Stanton Bruce A
Department of Physiology, Dartmouth Medical School, Hanover, NH, USA.
PLoS Pathog. 2009 Apr;5(4):e1000382. doi: 10.1371/journal.ppat.1000382. Epub 2009 Apr 10.
Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane-derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including beta-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma membrane. These virulence factors enter the cytoplasm of the host cell via N-WASP-mediated actin trafficking, where they rapidly distribute to specific subcellular locations to affect host cell biology. We propose that secreted virulence factors are not released individually as naked proteins into the surrounding milieu where they may randomly contact the surface of the host cell, but instead bacterial derived OMV deliver multiple virulence factors simultaneously and directly into the host cell cytoplasm in a coordinated manner.
细菌利用多种分泌型毒力因子来操纵宿主细胞，从而导致严重的发病和死亡。我们报告了一种将多种细菌毒力因子同时直接递送至宿主细胞胞质的机制，从而无需病原体与宿主细胞直接相互作用即可导致细胞毒性。我们发现，由机会致病菌铜绿假单胞菌分泌的外膜囊泡（OMV）通过OMV与宿主质膜中的脂筏融合，将多种毒力因子，包括β-内酰胺酶、碱性磷酸酶、溶血磷脂酶C和Cif，直接递送至宿主细胞质中。这些毒力因子通过N-WASP介导的肌动蛋白运输进入宿主细胞的细胞质，在那里它们迅速分布到特定的亚细胞位置以影响宿主细胞生物学。我们提出，分泌的毒力因子并非作为裸露的蛋白质单独释放到周围环境中，使其可能随机接触宿主细胞表面，而是细菌衍生的OMV以协调的方式将多种毒力因子同时直接递送至宿主细胞细胞质中。
