Activity and characterization of a pH-sensitive antimicrobial peptide

Publication date: Available online 8 May 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Morgan A. Hitchner, Luis E. Santiago-Ortiz, Matthew R. Necelis, David J. Shirley, Thaddeus J. Palmer, Katharine Tarnawsky, Timothy D. Vaden, Gregory A. CaputoAbstractAntimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules throughout evolution. Previous work showed that when Histidine was incorporated into the peptide C18G it lost antimicrobial activity. The role of pH on activity and biophysical properties of the peptide was investigated to explain this phenomenon. Minimal inhibitory concentration (MIC) results demonstrated that decreased media pH increased antimicrobial activity. Trichloroethanol (TCE) quenching and red-edge excitation spectroscopy (REES) showed a clear pH dependence on peptide aggregation in solution. Trp fluorescence was used to monitor binding to lipid vesicles and demonstrated the peptide binds to anionic bilayers at all pH values tested, however, binding to zwitterionic bilayers was enhanced at pH 7 and 8 (above the His pKa). Dual Quencher Analysis (DQA) confirmed the peptide inserted more deeply in PC:PG and PE:PG membranes, but could insert into PC bilayers at pH conditions above the His pKa. Bacterial membrane permeabilization assays which showed enhanced membrane perme...

Source: Biochimica et Biophysica Acta (BBA) Biomembranes - May 8, 2019 Category: Biochemistry Source Type: research