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Antimicrob Agents Chemother ; 60(4): 2326-35, 2016 Apr.
Article de Anglais | MEDLINE | ID: mdl-26833156

RÉSUMÉ

We have morphologically characterizedCandida tropicalisisolates resistant to amphotericin B (AmB). These isolates present an enlarged cell wall compared to isolates of regular susceptibility. This correlated with higher levels of ß-1,3-glucan in the cell wall but not with detectable changes in chitin content. In line with this, AmB-resistant strains showed reduced susceptibility to Congo red. Moreover, mitogen-activated protein kinases (MAPKs) involved in cell integrity were already activated during regular growth in these strains. Finally, we investigated the response elicited by human blood cells and found that AmB-resistant strains induced a stronger proinflammatory response than susceptible strains. In agreement, AmB-resistant strains also induced stronger melanization ofGalleria mellonellalarvae, indicating that the effect of alterations of the cell wall on the immune response is conserved in different types of hosts. Our results suggest that resistance to AmB is associated with pleiotropic mechanisms that might have important consequences, not only for the efficacy of the treatment but also for the immune response elicited by the host.


Sujet(s)
Amphotéricine B/pharmacologie , Antifongiques/pharmacologie , Candida tropicalis/effets des médicaments et des substances chimiques , Paroi cellulaire/effets des médicaments et des substances chimiques , Résistance des champignons aux médicaments , bêta-Glucanes/immunologie , Animaux , Candida tropicalis/génétique , Candida tropicalis/immunologie , Paroi cellulaire/composition chimique , Paroi cellulaire/immunologie , Chitine/immunologie , Chitine/métabolisme , Rouge Congo/pharmacologie , Interactions hôte-pathogène/immunologie , Humains , Immunité innée , Larve/effets des médicaments et des substances chimiques , Larve/immunologie , Larve/microbiologie , Agranulocytes/effets des médicaments et des substances chimiques , Agranulocytes/immunologie , Agranulocytes/microbiologie , Mélanines/génétique , Mélanines/immunologie , Tests de sensibilité microbienne , Mitogen-Activated Protein Kinases/génétique , Mitogen-Activated Protein Kinases/immunologie , Papillons de nuit/effets des médicaments et des substances chimiques , Papillons de nuit/immunologie , Papillons de nuit/microbiologie , bêta-Glucanes/métabolisme
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