Campylobacter jejuni cell lysates differently target mitochondria and lysosomes on HeLa cells.

B Canonico, R Campana, F Luchetti, M Arcangeletti, M Betti, E Cesarini, C Ciacci, E Vittoria, L Galli, S Papa, W Baffone

Apoptosis : an international journal on programmed cell death 2014 Aug

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Campylobacter jejuni is the most common cause of bacterial gastroenteritis in humans. The synthesis of cytolethal distending toxin appears essential in the infection process. In this work we evaluated the sequence of lethal events in HeLa cells exposed to cell lysates of two distinct strains, C. jejuni ATCC 33291 and C. jejuni ISS3. C. jejuni cell lysates (CCLys) were added to HeLa cell monolayers which were analysed to detect DNA content, death features, bcl-2 and p53 status, mitochondria/lysosomes network and finally, CD54 and CD59 alterations, compared to cell lysates of C. jejuni 11168H cdtA mutant. We found mitochondria and lysosomes differently targeted by these bacterial lysates. Death, consistent with apoptosis for C. jejuni ATCC 33291 lysate, occurred in a slow way (>48 h); concomitantly HeLa cells increase their endolysosomal compartment, as a consequence of toxin internalization besides a simultaneous and partial lysosomal destabilization. C. jejuni CCLys induces death in HeLa cells mainly via a caspase-dependent mechanism although a p53 lysosomal pathway (also caspase-independent) seems to appear in addition. In C. jejuni ISS3-treated cells, the p53-mediated oxidative degradation of mitochondrial components seems to be lost, inducing the deepest lysosomal alterations. Furthermore, CD59 considerably decreases, suggesting both a degradation or internalisation pathway. CCLys-treated HeLa cells increase CD54 expression on their surface, because of the action of lysate as its double feature of toxin and bacterial peptide. In conclusion, we revealed that C. jejuni CCLys-treated HeLa cells displayed different features, depending on the particular strain.

Citation

B Canonico, R Campana, F Luchetti, M Arcangeletti, M Betti, E Cesarini, C Ciacci, E Vittoria, L Galli, S Papa, W Baffone. Campylobacter jejuni cell lysates differently target mitochondria and lysosomes on HeLa cells. Apoptosis : an international journal on programmed cell death. 2014 Aug;19(8):1225-42