TY - JOUR
T1 - Activation of melanin synthesis in Alternaria infectoria by antifungal drugs
AU - Fernandes, Chantal
AU - Prados-Rosales, Rafael
AU - Silva, Branca M.A.
AU - Nakouzi-Naranjo, Antonio
AU - Zuzarte, Mónica
AU - Chatterjee, Subhasish
AU - Stark, Ruth E.
AU - Casadevall, Arturo
AU - Gonçalves, Teresa
N1 - Funding Information:
We thank the Thermodynamics/Solid State Chemistry Laboratory, SER Group, Coimbra Chemistry Center, for FTIR spectroscopy. This study was partly supported by a project funded by the Fundação para a Ciência e Tecnologia (FCT), PTDC/SAU-ESA/108636/2008, cofunded by COMPETE-Operational Programme Competitiveness Factors and FEDER, by FEDER funds through COMPETE, and by national funds provided by FCT under strategic project UID/NEU/04539/2013. C.F. is the recipient of a postdoctoral fellowship from FCT (SFRH/BPD/63733/ 2009). B.M.A.S. was the recipient of a research fellowship within the scope of FCT project PTDC/SAU-ESA/108636/2008. This research was also supported by a grant from the National Institutes of Health (NIH R01- AI052733). The 600-MHz NMR facilities used in this work are operated by the City College of New York and the City University of New York Institute for Macromolecular Assemblies, with additional infrastructural support being provided by grant 8G12 MD007603-29 from the National Institute on Minority Health and Health Disparities of the National Institutes of Health.
Publisher Copyright:
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016/3
Y1 - 2016/3
N2 - The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis.
AB - The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis.
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U2 - 10.1128/AAC.02190-15
DO - 10.1128/AAC.02190-15
M3 - Article
C2 - 26711773
AN - SCOPUS:84960157065
SN - 0066-4804
VL - 60
SP - 1646
EP - 1655
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 3
ER -