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Title: Effects of microplusin, a copper-chelating antimicrobial peptide, against Cryptococcus neoformans
Authors: Silva, Fernanda D.
Rossi, Diego C. P.
Martinez, Luis R.
Frases, Susana
Fonseca, Fernanda L.
Campos, Claudia Barbosa L. [UNIFESP]
Rodrigues, Marcio L.
Nosanchuk, Joshua D.
Daffre, Sirlei
Universidade de São Paulo (USP)
Long Isl Univ CW Post
Albert Einstein Coll Med
Inst Nacl Metrol Normalizacao & Qualidade Ind
Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Keywords: microplusin
antimicrobial peptide
Cryptococcus neoformans
Issue Date: 1-Nov-2011
Publisher: Wiley-Blackwell
Citation: Fems Microbiology Letters. Malden: Wiley-Blackwell, v. 324, n. 1, p. 64-72, 2011.
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 (MIC(50) = 0.09 mu M), 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.
ISSN: 0378-1097
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