The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex.
Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs.
Department of Clinical Medicine, School of Medicine, Post-Graduation Program in Medicine Science, Federal University of Ceará, Fortaleza, Ceará, Brazil.|Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Rossana de Aguiar
RA
Cordeiro
Department of Clinical Medicine, School of Medicine, Post-Graduation Program in Medicine Science, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Ramila de Brito
RB
Macedo
Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Carlos Eduardo Cordeiro
CEC
Teixeira
Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Francisca Jakelyne de Farias
FJF
Marques
Christus College, School of Medicine, Fortaleza, Ceará, Brazil.|LabPasteur-DASA Laboratory, Fortaleza, Ceará, Brazil.|Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Tereza de Jesus Pinheiro Gomes
TJPG
Bandeira
Department of Pathology and Legal Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
José Luciano Bezerra
JLB
Moreira
Department of Clinical Medicine, School of Medicine, Post-Graduation Program in Medicine Science, Federal University of Ceará, Fortaleza, Ceará, Brazil.|Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Raimunda Sâmia Nogueira
RSN
Brilhante
School of Veterinary, Postgraduate Program in Veterinary Science, State University of Ceará, Fortaleza, Ceará, Brazil.|Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Marcos Fábio Gadelha
MFG
Rocha
Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
José Júlio Costa
JJC
Sidrim
D000666:Amphotericin B / Q000493:pharmacokinetics / Q000494:pharmacology*; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects*; D000077336:Caspofungin; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D054714:Echinocandins / Q000493:pharmacokinetics / Q000494:pharmacology*; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D016572:Cyclosporine; D000077336:Caspofungin; D065819:Voriconazole