An Amphipathic Undecapeptide with All d-Amino Acids Shows Promising Activity against Colistin-Resistant Strains of Acinetobacter baumannii and a Dual Mode of Action
ABSTRACTMultiple strains ofAcinetobacter baumanniihave developed multidrug resistance (MDR), leaving colistin as the only effective treatment. The cecropin-α–melittin hybrid BP100 (KKLFKKILKYL-NH2) and its analogs have previously shown activity against a wide array of plant and human pathogens. In this study, we investigated thein vitroantibacterial activities of 18 BP100 analogs (four known and 14 new) against the MDRA. baumanniistrain ATCC BAA-1605, as well as against a number of other clinically relevant human pathogens. Selected peptides were further evaluated against strains ofA. baumanniithat acquired resistance to colistin due to mutations of thelpxC,lpxD,pmrA, andpmrBgenes. The novel analogue BP214 showed antimicrobial activity at 1 to 2 μM and a hemolytic 50% effective concentration (EC50) of >150 μM. The lower activity of its enantiomer suggests a dual, specific and nonspecific mode of action. Interestingly, colistin behaved antagonistically to BP214 whenpmrABandlpxCmutants were challenged.