title: Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host.
abstract: 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 β-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.
authors.affiliation: National Centre for Microbiology, Mycology Reference Laboratory, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain Dermatology Research Group, University of Antioquia, Medellín, Colombia.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Mesa-Arango
authors.affiliation: National Centre for Microbiology, Mycology Reference Laboratory, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rueda
authors.affiliation: Department of Microbiology II, Faculty of Pharmacy, Complutense University, Madrid, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Román
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Quintin
authors.affiliation: National Centre for Microbiology, Electron and Confocal Microscopy Unit, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Terrón
authors.affiliation: National Centre for Microbiology, Electron and Confocal Microscopy Unit, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Luque
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Microbiology II, Faculty of Pharmacy, Complutense University, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pla
authors.affiliation: National Centre for Microbiology, Mycology Reference Laboratory, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain ozaragoza@isciii.es.
authors.forename: Oscar
authors.initials: O
authors.lastname: Zaragoza
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D041022:Candida tropicalis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D002686:Chitin / Q000276:immunology / Q000378:metabolism; D003224:Congo Red / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007814:Larva / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008543:Melanins / Q000235:genetics / Q000276:immunology; D008826:Microbial Sensitivity Tests; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D009036:Moths / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D047071:beta-Glucans / Q000276:immunology* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D008543:Melanins; D047071:beta-Glucans; D002686:Chitin; D003224:Congo Red; D000666:Amphotericin B; C033363:beta-1,3-glucan; D020928:Mitogen-Activated Protein Kinases
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