Effects of microplusin, a copper-chelating antimicrobial peptide, against Cryptococcus neoformans

• Published in: FEMS microbiology letters 2011-11, Vol.324 (1), p.64-72
• Main Authors: Silva, Fernanda D., Rossi, Diego C.P., Martinez, Luis R., Frases, Susana, Fonseca, Fernanda L., Campos, Claudia Barbosa L., Rodrigues, Marcio L., Nosanchuk, Joshua D., Daffre, Sirlei
• Format: Article
• Language: English
• Subjects: Antifungal Agents - metabolism; Antifungal Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial Cationic Peptides - metabolism; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptide; Antimicrobial peptides; Biological and medical sciences; Chelating Agents - metabolism; Chelation; Copper; Copper - metabolism; Cryptococcosis; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Etiology; Fundamental and applied biological sciences. Psychology; Fungal infections; Fungi; Laccase; Melanization; Microbial Sensitivity Tests; Microbiology; microplusin; Miscellaneous; Mycology; Oxygen - metabolism; Peptides; Polysaccharides; Respiration; Supplements; Virulence; Virulence factors
• ISSN: 0378-1097; 1574-6968
• DOI: 10.1111/j.1574-6968.2011.02386.x

Abstract Microplusin is an antimicrobial peptide isolated from the cattle tick Rhipicephalus (Boophilus) microplus. Its copper-chelating ability is putatively responsible for its bacteriostatic activity against Micrococcus luteus as microplusin inhibits respiration in this species, which is a copper-dependent process. Microplusin is also active against Cryptococcus neoformans (MIC50 = 0.09 μM), the etiologic agent of cryptococcosis. Here, we show that microplusin is fungistatic to C. neoformans and this inhibitory effect is abrogated by copper supplementation. Notably, microplusin drastically altered the respiratory profile of C. neoformans. In addition, microplusin affects important virulence factors of this fungus. We observed that microplusin completely inhibited fungal melanization, and this effect correlates with the inhibition of the related enzyme laccase. Also, microplusin significantly inhibited the capsule size of C. neoformans. Our studies reveal, for the first time, a copper-chelating antimicrobial peptide that inhibits respiration and growth of C. neoformans and modifies two major virulence factors: melanization and formation of a polysaccharide capsule. These features suggest that microplusin, or other copper-chelation approaches, may be a promising therapeutic for cryptococcosis.