Mechanistic and phenotypic studies of bicarinalin, BP100 and colistin action on Acinetobacter baumannii

Acinetobacter baumannii has been identified by the WHO as a high priority pathogen. It can be resistant to multiple antibiotics and colistin sulphate is often used as a last-resort treatment. However, the potentially severe side-effects of colistin are well documented and this study compared the bactericidal and anti-biofilm activity of two synthetic nature-inspired antimicrobial peptides, bicarinalin and BP100, with colistin. The minimum bactericidal concentration (MBC) against planktonic A. baumannii was approximately 0.5 μg/ml for colistin sulphate and ∼4 μg/ml for bicarinalin and BP100. A. baumannii commonly occurs as a biofilm and biofilm removal assay results highlighted that both bicarinalin and BP100 had significantly greater potential than colistin. Atomic force microscopy (AFM) showed dramatic changes in A. baumannii cell size and surface conformity when treated with peptide concentrations at and above the MBC. Scanning electron microscopy (SEM) visualised the reduction of biofilm coverage and cell surface changes as peptide concentration increased. Liposome assays revealed that these peptides most likely act as pore-forming agents in the membrane. Bicarinalin and BP100 may be effective therapeutic alternatives to colistin against A. baumannii infections but further research is required to assess if they elicit cytotoxicity issues in patients.