| Grant number: | 13/12338-6 |
| Support Opportunities: | Regular Research Grants |
| Start date: | October 01, 2013 |
| End date: | September 30, 2015 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Fernanda Dias da Silva |
| Grantee: | Fernanda Dias da Silva |
| Host Institution: | Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil |
| Associated researchers: | Claudia Barbosa Ladeira de Campos ; Jose Ricardo Murari Pires ; Sirlei Daffre ; Wanius José Garcia da Silva |
Abstract
Microplusin is a copper and iron chelating peptide, present in the cattle tick Riphicephalus (Boophilus) microplus. It has a globular structure, arranged in five ±-helices and is rich in histidine and cysteine amino acids residues. The histidines H-1, H-2 and H-74 were among the possible amino acids involved in forming the binding site for copper. In addition to its chelating ability, microplusin showed antimicrobial activity against species of Gram-positive bacteria and fungi, with bacteriostatic and fungistatic effects observed against Micrococcus luteus and Cryptococcus neoformans, respectively. Its main action mechanism seems to involve the hijacking of copper from the medium, making this micronutrient unavailable for microorganisms. In fact, it was observed that cultures of M. luteus and C. neoformans treated with the peptide showed a reduction in their consumption of oxygen and experimental data suggest that depletion of copper may have affected the activity of heme copper oxidases belonging to one of the pathways of electron transport chain. Microplusin also inhibited two important virulence factors of C. neoformans: melanin synthesis and formation of the capsule of polysaccharides. The absence of melanization is related to an observed decrease in the activity of laccase, a copper dependent enzyme. The characteristics of microplusin indicate its enormous potential as drug and studies on which amino acids in its sequence are important for maintenance of its structure and activities become essential for their applicability are fully exploited. Therefore, this project aims to evaluate the effect of removal and/or replacement of certain amino acid residues of microplusin, with emphasis on histidines, on its chelating and antimicrobial activities. The obtained results may indicate which histidine residues are essential for the formation of the copper-binding site of microplusin and whether the integrity of this site is essential to its action against bacteria and fungi. (AU)
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