1. Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host
- Author
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Jesús Pla, Ana Cecilia Mesa-Arango, Mihai G. Netea, Elvira Román, Cristina Rueda, Jessica Quintin, Oscar Zaragoza, María C. Terrón, Daniel Luque, Instituto de Salud Carlos III [Madrid] (ISC), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Radboud University Medical Center [Nijmegen], and A. C. Mesa-Arango has been supported by fellowships from Fundación Carolina and Instituto de Salud Carlos III. C. Rueda has a Sara Borrell contract from the Fondo de Investigaciones Sanitarias (reference no. CD11/00110).
- Subjects
0301 basic medicine ,Antifungal Agents ,beta-Glucans ,[SDV]Life Sciences [q-bio] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Chitin ,Drug resistance ,Moths ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,MESH: Candida tropicalis ,MESH: Chitin ,Candida tropicalis ,MESH: Melanins ,Cell Wall ,Amphotericin B ,Pharmacology (medical) ,MESH: Animals ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology ,MESH: Microbial Sensitivity Tests ,MESH: beta-Glucans ,Kinase ,MESH: Moths ,3. Good health ,MESH: Leukocytes, Mononuclear ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Larva ,Host-Pathogen Interactions ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: Immunity, Innate ,Mitogen-Activated Protein Kinases ,medicine.drug ,030106 microbiology ,Microbial Sensitivity Tests ,Biology ,Microbiology ,Proinflammatory cytokine ,MESH: Drug Resistance, Fungal ,Cell wall ,03 medical and health sciences ,Immune system ,MESH: Cell Wall ,Drug Resistance, Fungal ,Mechanisms of Resistance ,Immunity ,MESH: Amphotericin B ,medicine ,Animals ,Humans ,Melanins ,Pharmacology ,MESH: Humans ,MESH: Host-Pathogen Interactions ,Congo Red ,biology.organism_classification ,MESH: Antifungal Agents ,MESH: Mitogen-Activated Protein Kinases ,Immunity, Innate ,MESH: Congo Red ,Leukocytes, Mononuclear ,MESH: Larva - Abstract
We have morphologically characterized Candida tropicalis isolates 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 of Galleria mellonella larvae, 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.
- Published
- 2016