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Title

PH-dependent solution structure and activity of a reduced form of the host-defense peptide myticin C (Myt C) from the mussel mytilus galloprovincialis

AuthorsMartínez-López, Alicia; Encinar, José Antonio; Medina-Gali, Regla María; Balseiro, P. ; García-Valtanen, Pablo; Figueras Huerta, Antonio ; Novoa, Beatriz ; Estepa, Amparo
KeywordsMyticin
Mussel
HDPs
AMPs
VHSV
Chemotaxis
PH
Structure
Infrared spectroscopic
Liposomes
Issue Date4-Jul-2013
PublisherMultidisciplinary Digital Publishing Institute
CitationMarine Drugs 11(7): 2328-2346 (2013)
AbstractMyticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”.
Description19 páginas, 6 figuras
Publisher version (URL)http://dx.doi.org/10.3390/md11072328
URIhttp://hdl.handle.net/10261/81116
DOI10.3390/md11072328
ISSN1660-3397
Appears in Collections:(IIM) Artículos
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