Activation of melanin synthesis in Alternaria infectoria by antifungal drugs

Chantal Fernandes, Rafael Prados-Rosales, Branca M.A. Silva, Antonio Nakouzi-Naranjo, Mónica Zuzarte, Subhasish Chatterjee, Ruth E. Stark, Arturo Casadevall, Teresa Gonçalves

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1646-1655
Number of pages10
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number3
DOIs
StatePublished - Mar 2016

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Fernandes, C., Prados-Rosales, R., Silva, B. M. A., Nakouzi-Naranjo, A., Zuzarte, M., Chatterjee, S., Stark, R. E., Casadevall, A., & Gonçalves, T. (2016). Activation of melanin synthesis in Alternaria infectoria by antifungal drugs. Antimicrobial agents and chemotherapy, 60(3), 1646-1655. https://doi.org/10.1128/AAC.02190-15