| Autor: |
Rompikuntal, Pramod Kumar, Thay, Bernard, Khan, Muhammad Khanzeb, Alanko, Jonna, Penttinen, Anna-Maija, Asikainen, Sirkka, Wai, Sun Nyunt, Oscarsson, Jan |
| Zdroj: |
Infection and Immunity; November 2011, Vol. 80 Issue: 1 p31-42, 12p |
| Abstrakt: |
ABSTRACTAggregatibacter actinomycetemcomitansis implicated in aggressive forms of periodontitis. Similarly to several other Gram-negative species, this organism produces and excretes a cytolethal distending toxin (CDT), a genotoxin associated with cell distention, G2cell cycle arrest, and/or apoptosis in many mammalian cell types. In this study, we have identified A. actinomycetemcomitansouter membrane vesicles (OMVs) as a vehicle for simultaneous delivery of multiple proteins, including CDT, into human cells. The OMV proteins were internalized in both HeLa cells and human gingival fibroblasts (HGF) via a mechanism of OMV fusion with lipid rafts in the plasma membrane. The active toxin unit, CdtB, was localized inside the nucleus of the intoxicated cells, whereas OmpA and proteins detected using an antibody specific to whole A. actinomycetemcomitansserotype a cells had a perinuclear distribution. In accordance with a tight association of CdtB with OMVs, vesicles isolated from A. actinomycetemcomitansstrain D7SS (serotype a), in contrast to OMVs from a D7SS cdtABCmutant, induced a cytolethal distending effect on HeLa and HGF cells, indicating that OMV-associated CDT was biologically active. Association of CDT with OMVs was also observed in A. actinomycetemcomitansisolates belonging to serotypes b and c, indicating that OMV-mediated release of CDT may be conserved in A. actinomycetemcomitans. Although the role of A. actinomycetemcomitansOMVs in periodontal disease has not yet been elucidated, our present data suggest that OMVs could deliver biologically active CDT and additional virulence factors into susceptible cells of the periodontium. |
| Databáze: |
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