Clostridium difficile spore-macrophage interactions: Spore survival

Daniel Paredes-Sabja, Glenda Cofre-Araneda, Christian Brito-Silva, Marjorie Pizarro-Guajardo, Mahfuzur R. Sarker

Resultado de la investigación: Article

31 Citas (Scopus)

Resumen

Background: Clostridium difficile is the main cause of nosocomial infections including antibiotic associated diarrhea, pseudomembranous colitis and toxic megacolon. During the course of Clostridium difficile infections (CDI), C. difficile undergoes sporulation and releases spores to the colonic environment. The elevated relapse rates of CDI suggest that C. difficile spores has a mechanism(s) to efficiently persist in the host colonic environment. Methodology/Principal Findings: In this work, we provide evidence that C. difficile spores are well suited to survive the host's innate immune system. Electron microscopy results show that C. difficile spores are recognized by discrete patchy regions on the surface of macrophage Raw 264.7 cells, and phagocytosis was actin polymerization dependent. Fluorescence microscopy results show that >80% of Raw 264.7 cells had at least one C. difficile spore adhered, and that ~60% of C. difficile spores were phagocytosed by Raw 264.7 cells. Strikingly, presence of complement decreased Raw 264.7 cells' ability to phagocytose C. difficile spores. Due to the ability of C. difficile spores to remain dormant inside Raw 264.7 cells, they were able to survive up to 72 h of macrophage infection. Interestingly, transmission electron micrographs showed interactions between the surface proteins of C. difficile spores and the phagosome membrane of Raw 264.7 cells. In addition, infection of Raw 264.7 cells with C. difficile spores for 48 h produced significant Raw 264.7 cell death as demonstrated by trypan blue assay, and nuclei staining by ethidium homodimer-1. Conclusions/Significance: These results demonstrate that despite efficient recognition and phagocytosis of C. difficile spores by Raw 264.7 cells, spores remain dormant and are able to survive and produce cytotoxic effects on Raw 264.7 cells.

Idioma originalEnglish
Número de artículoe43635
PublicaciónPLoS ONE
Volumen7
N.º8
DOI
EstadoPublished - 27 ago 2012

Huella dactilar

Clostridium difficile
Clostridium
Macrophages
Spores
macrophages
spores
Trypan Blue
Immune system
Poisons
Fluorescence microscopy
Cell death
Protein C
Electron microscopy
Actins
Assays
Membrane Proteins
Polymerization
Anti-Bacterial Agents
cells
Phagocytosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Citar esto

Paredes-Sabja, D., Cofre-Araneda, G., Brito-Silva, C., Pizarro-Guajardo, M., & Sarker, M. R. (2012). Clostridium difficile spore-macrophage interactions: Spore survival. PLoS ONE, 7(8), [e43635]. https://doi.org/10.1371/journal.pone.0043635
Paredes-Sabja, Daniel ; Cofre-Araneda, Glenda ; Brito-Silva, Christian ; Pizarro-Guajardo, Marjorie ; Sarker, Mahfuzur R. / Clostridium difficile spore-macrophage interactions : Spore survival. En: PLoS ONE. 2012 ; Vol. 7, N.º 8.
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Paredes-Sabja, D, Cofre-Araneda, G, Brito-Silva, C, Pizarro-Guajardo, M & Sarker, MR 2012, 'Clostridium difficile spore-macrophage interactions: Spore survival', PLoS ONE, vol. 7, n.º 8, e43635. https://doi.org/10.1371/journal.pone.0043635

Clostridium difficile spore-macrophage interactions : Spore survival. / Paredes-Sabja, Daniel; Cofre-Araneda, Glenda; Brito-Silva, Christian; Pizarro-Guajardo, Marjorie; Sarker, Mahfuzur R.

En: PLoS ONE, Vol. 7, N.º 8, e43635, 27.08.2012.

Resultado de la investigación: Article

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AU - Sarker, Mahfuzur R.

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Paredes-Sabja D, Cofre-Araneda G, Brito-Silva C, Pizarro-Guajardo M, Sarker MR. Clostridium difficile spore-macrophage interactions: Spore survival. PLoS ONE. 2012 ago 27;7(8). e43635. https://doi.org/10.1371/journal.pone.0043635