Antimicrobial activity of histidine-rich peptides is dependent on acidic conditions |
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Authors: | Lukasz Kacprzyk,Victoria Rydengå rd,Matthias Mö rgelin,Mukesh Pasupuleti,Artur Schmidtchen |
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Affiliation: | a Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Kraków, Poland b Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden c Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden d Department of Pharmacy, Uppsala University, SE-75123, Uppsala, Sweden |
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Abstract: | Synthetic peptides composed of multiples of the consensus heparin-binding Cardin and Weintraub sequences AKKARA and ARKKAAKA are antimicrobial. Replacement of lysine and arginine by histidine in these peptides completely abrogates their antimicrobial and heparin-binding activities at neutral pH. However, the antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) as well as the fungus Candida albicans, was restored at acidic conditions (pH 5.5). Fluorescence microscopy and FACS analysis showed that the binding of the histidine-rich peptides to E. coli and Candida was significantly enhanced at pH 5.5. Likewise, fluorescence studies for assessment of membrane permeation as well as electron microscopy analysis of peptide-treated bacteria, paired with studies of peptide effects on liposomes, demonstrated that the peptides induce membrane lysis only at acidic pH. No discernible hemolysis was noted for the histidine-rich peptides. Similar pH-dependent antimicrobial activities were demonstrated for peptides derived from histidine-rich and heparin-binding regions of human kininogen and histidine-rich glycoprotein. The results demonstrate that the presence of an acidic environment is an important regulator of the activity of histidine-rich antimicrobial peptides. |
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Keywords: | AMP, antimicrobial peptide GAG, glycosaminoglycan hCAP-18, human cationic antimicrobial protein 18 HMWK, High-molecular weight kininogen MALDI-TOF, matrix-assisted laser desorption/ ionization-time of flight MES, 2-(morpholino)-ethanesulfonic acid PIPES, piperazine-1,4-bis(2-ethanesulfonic acid) TR, Texas red Tris, trishydroxymethylaminomethane |
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