Mecanismo de ação da microplusina, um peptídeo quelante de cobre com atividade antimicrobiana. / Action mechanism of microplusin, a copper chelating peptide with antimicrobial activity.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Antimicrobial peptides (AMPs) take part of innate immune mechanisms against infections. Microplusin is a 10,204 Da AMP, isolated from cell-free hemolymph and eggs of the tick Rhipicephalus (Boophilus) microplus. It is an anionic AMP at physiological pH, with six cysteine residues forming three disulfide bridges and seven histidine residues clustered mainly at the carboxy end portion. The goal of the present work was investigate the antimicrobial action mechanism of microplusin. Recombinant microplusin is active against Gram-positive bacteria and fungi, however, no activity is detected for Gram-negative bacteria. Two models were used to evaluate the action mechanism of microplusin: the bacteria Micrococcus luteus and the yeast Cryptococcus neoformans. Microplusin is bacteriostatic against M. luteus and its localization is intracellular for these bacteria. Moreover, microplusin binds copper and the addition of this metal into the medium reduces its antibacterial activity. M. luteus bacteria pre-treated with microplusin recover its growth when copper is added. These data indicate that microplusin activity is related to its ability to deplete copper present in the extracellular or intracellular environment, suggesting a nutritional effect. Microplusin presents a tertiary structure with five a-helix and the copper binding does not induce conformation changes. In addition, it was observed that histidines 1, 2 and 74 from microplusin may be involved in the formation of a copper binding site. About C. neoformans, it was verified microplusin inhibits its melanization, a virulence factor catalyzed by laccase, a copper dependent enzyme. However, microplusin does affect neither laccase activity nor its gene expression. The melanization caused by auto-polymerazation of phenolic substrates, is also not inhibited by microplusin. Hence, additional studies are required to evaluate the mechanism by which microplusin inhibits melanization. In addition, microplusin also affects the fungi viability and reduces the capsule size, another important virulence factor.The microplusin activities against C. neoformans suggest its therapeutic potential. In vivo experiments with murine model showed that microplusin reduces the inflammation and the viability of C. neoformans in the lungs, indicating that, in optimized conditions, the peptide may act in the infection control.

ASSUNTO(S)

action mechanism antifúngico quelante de cobre antifungal peptídeo antimicrobiano antibacterial mecanismo de ação copper chelating tick antimicrobial peptide antibacteriano carrapato

ACESSO AO ARTIGO

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