Long-Distance Delivery of Bacterial Virulence Factors by Pseudomonas aeruginosa Outer Membrane Vesicles

By J. Bomberger, Daniel P Maceachran, B. Coutermarsh, Siying Ye, G. O’Toole, B. Stanton. PLoS Pathogens, 2009

608 citations recorded by the source corpus.

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 β-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.

Subfields: Microbiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a229a445a05588c442204021bcfa63b438081d30

How researchers see this paper

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In Microbiology

1. M. Kuehn

In Molecular Biology

1. Rienk Nieuwland
2. Min Wu
3. M. Kuehn
4. P. Harrison
5. Edwin van der Pol
6. A. Sturk
7. A. Böing

Citations in the corpus

• Virulence and Immunomodulatory Roles of Bacterial Outer Membrane Vesicles (2010, background): “aeruginosa CiF protein is preferentially secreted into vesicles, and CiF-containing vesicles decrease levels of apical lung epithelial expression of the cystic fibrosis transmembrane conductance regulator protein (CFTR), the central protein in the genetic disease of cystic fibrosis (15, 91).”
• Classification, Functions, and Clinical Relevance of Extracellular Vesicles (2012, background): “For instance, the OMVs of P. aeruginosa contain virulence factors, such as phospholipase C, -lactamase, and proteases, that can be delivered into the cytoplasm of cells after membrane fusion, thereby killing these cells (Kadurugamuwa and Beveridge, 1995; Bomberger et al., 2009).”
• Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics (2022, background): “While OMVs are detrimental to the host by delivering antibiotic resistance molecules or enzymes (β-lactamase), they have been harnessed as alternative delivery vehicles for transporting treatments or vaccines for various diseases including infection and cancer.(47,238)”