We have investigated structural changes of peptides related to antimicrobial peptide Halictine-1 (HAL-1) induced by interaction with various membrane-mimicking models with the aim to identify a mechanism of the peptide mode of action and to find a correlation between changes of primary/secondary structure and biological activity. Modifications in the HAL-1 amino acid sequence at particular positions, causing an increase of amphipathicity (Arg/Lys exchange), restricted mobility (insertion of Pro) and consequent changes in antimicrobial and hemolytic activity, led to different behavior towards model membranes. Secondary structure changes induced by peptide-membrane interaction were studied by circular dichroism, infrared spectroscopy, and fluorescence spectroscopy. The experimental results were complemented by molecular dynamics calculations. An α-helical structure has been found to be necessary but not completely sufficient for the HAL-1 peptides antimicrobial action. The role of alternative conformations (such as β-sheet, PPII or 310-helix) also seems to be important. A mechanism of the peptide mode of action probably involves formation of peptide assemblies (possibly membrane pores), which disrupt bacterial membrane and, consequently, allow membrane penetration.

• Klíčová slova
• antibacterial peptides, circular dichroism, fluorescence, halictine, infrared spectroscopy,
• MeSH
• antibakteriální látky chemie   metabolismus   MeSH
• fosfatidylcholiny chemie   MeSH
• fosfatidylglyceroly chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• kationické antimikrobiální peptidy chemie   metabolismus   MeSH
• kinetika MeSH
• konformace proteinů, alfa-helix MeSH
• konformace proteinů, beta-řetězec MeSH
• lipidové dvojvrstvy chemie   MeSH
• permeabilita MeSH
• sekvence aminokyselin MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• fosfatidylcholiny MeSH
• fosfatidylglyceroly MeSH
• kationické antimikrobiální peptidy MeSH
• lipidové dvojvrstvy MeSH

Joint replacement infections and osteomyelitis are among the most serious complications in orthopaedics and traumatology. The risk factors for these infections are often bacterial resistance to antimicrobials. One of the few solutions available to control bacterial resistance involves antimicrobials, which have a different mechanism of action from traditional antibiotics. Antimicrobial peptides (AMP) appear to be highly promising candidates in the treatment of resistant infections. We have identified several AMP in the venom of various wild bees and designed analogues that show potent antimicrobial activity and low toxicity against eukaryotic cells. The aim of the present study was to test the efficacy of one of those synthetic peptide analogues for the treatment of acute osteomyelitis invoked in laboratory rats. Femoral cavities of 20 laboratory Wistar rats were infected with Staphylococcus aureus. After 1 week, eight rats received an injectable calcium phosphate carrier alone, another eight rats were treated with a calcium phosphate mixed with AMP, and four rats were left without any further treatment. After another week, all rats were euthanized and radiographs were made of both the operated and healthy limbs. The animals with the carrier alone exhibited more severe acute osteomyelitis on radiographs in comparison to the recipients of the calcium phosphate carrier loaded AMP and untreated infected individuals. Based on the results of the above mentioned experiment, it was concluded that when injected directly into the site of femoral acute osteomyelitis, the calcium phosphate carrier mixed with AMP reduced osteomyelitis signs visible on radiographs.

• MeSH
• antibakteriální látky aplikace a dávkování   MeSH
• fosforečnany vápenaté farmakologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• osteomyelitida farmakoterapie   mikrobiologie   MeSH
• peptidy aplikace a dávkování   MeSH
• potkani Wistar MeSH
• stafylokokové infekce farmakoterapie   mikrobiologie   MeSH
• Staphylococcus aureus účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• calcium phosphate MeSH Prohlížeč
• fosforečnany vápenaté MeSH
• peptidy MeSH