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Cysteine peptidase B regulates Leishmania mexicana virulence through the modulation of GP63 expression

Casgrain, Pierre-André; Martel, Caroline; McMaster, W. Robert; Mottram, Jeremy; Olivier, Martin; Descoteaux, Albert . Cysteine peptidase B regulates Leishmania mexicana virulence through the modulation of GP63 expression In: 16e symposium annuel de parasitologie moléculaire du Québec, 6-7 juin 2016, Université McGill, Montréal, QC.

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Résumé

mechanism(s) by which the cysteine peptidase CPB contributes to L. mexicana virulence. We initially examined the impact of L. mexicana infection on the trafficking of VAMP3 and VAMP8, two endocytic SNARE proteins associated with phagolysosome biogenesis and function. Using a CPB-deficient mutant, we found that both VAMP3 and VAMP8 were down-modulated in a CPB-dependent manner. We also discovered that expression of the virulence-associated GPI-anchored metalloprotease GP63 was inhibited in the absence of CPB. Expression of GP63 in the CPB-deficient mutant was sufficient to downmodulate VAMP3 and VAMP8. Similarly, episomal expression of GP63 enabled the CPB deficient mutant to establish infection in macrophages, induce the formation large parasitophorous vacuoles, and cause lesions in mice. These findings implicate CPB in the regulation of GP63 expression and provide evidence that both GP63 and CPB are key virulence factors in L. mexicana.

Type de document: Document issu d'une conférence ou d'un atelier
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 mai 2018 20:11
Dernière modification: 01 mai 2018 20:11
URI: http://espace.inrs.ca/id/eprint/7065

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