RESUMO
We performed structural and functional studies of minibactenecin mini-ChBac7.5Nα, a natural proline-rich cathelicidin from domestic goat Capra hircus. To identify the key residues important for the biological action of the peptide, a panel of its alanine-substituted analogues was produced. The development of E. coli resistance to the natural minibactenecin, as well as to its analogues carrying substitutions for hydrophobic amino acids in the C-terminal residues was studied. The data obtained indicate the possibility of rapid development of the resistance to this class of peptides. The main factors in the formation of the antibiotic resistance are various mutations leading to inactivation of the SbmA transporter.
Assuntos
Peptídeos Antimicrobianos , Escherichia coli , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Prolina/farmacologia , Peptídeos/metabolismo , Leucócitos/metabolismo , Cabras/genética , Cabras/metabolismoRESUMO
Recombinant analogs of a number of natural host-defense mammalian cathelicidins were obtained and predominant mechanism of their antibacterial action was studied. The ability of cathelicidins to suppress the growth of Pseudomonas aeruginosa producing metallo-ß-lactamases (MßL) was studied, and the possibility of appearance of cathelicidin-resistant bacteria was evaluated. Among peptides with different structures and mechanisms of action, only the strains resistant to ChMAP-28 were not obtained, which indicated minimum risk of the development of natural resistance to this cathelicidin. High antibacterial activity, wide spectrum of action, and the absence of cross-resistance effects allow considering ChMAP-28 peptide as a candidate to be developed further as a therapeutic agent against MßL-producing bacteria.
Assuntos
Catelicidinas , Pseudomonas aeruginosa , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Catelicidinas/química , Catelicidinas/farmacologia , Mamíferos , Testes de Sensibilidade Microbiana , beta-LactamasesRESUMO
We studied combined effects of antimicrobial peptide arenicin-1 from lugworm Arenicola marina and some conventional antibiotics. A number of drug combinations with pronounced synergistic effects were revealed. The influence of antibacterial activity assessment conditions was determined and the methodology excluding false-positive test results was developed.
Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Escherichia coli/efeitos dos fármacos , Proteínas de Helminto/farmacologia , Poliquetos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Cloranfenicol/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Escherichia coli/crescimento & desenvolvimento , Proteínas de Helminto/isolamento & purificação , Testes de Sensibilidade Microbiana , Poliquetos/fisiologia , Polimixina B/farmacologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Tetraciclinas/farmacologia , beta-Lactamas/farmacologiaRESUMO
Antimicrobial peptides (AMPs) are evolutionarily ancient factors of the innate immune system that serve as a crucial first line of defense for humans, animals, and plants against infection. This review focuses on the structural organization, biosynthesis, and biological functions of AMPs that possess a ß-hairpin spatial structure. Representatives of this class of AMPs are among the most active antibiotic molecules of animal origin. Due to their wide spectrum of activity and resistance to internal environmental factors, natural ß-hairpin AMPbased compounds might become the most promising drug candidates.
