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

Abstract

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.

Pan-Drug Resistant Acinetobacter baumannii, but Not Other Strains, Are Resistant to the Bee Venom Peptide Melittin

“…The negative control was LB broth without bacteria and A. baumannii (ATCC 19606) was used as a positive control for biofilm production. To quantify the inhibitory effect of melittin peptide on biofilm growth, the method above was employed with some modifications [43]. After overnight incubation, the culture medium was removed and 100 µL of LB broth with melittin (14 µg/mL) was added.…”

Bactericidal and Anti-Biofilm Activity of the FtsZ Inhibitor C109 against Acinetobacter baumannii

“…The minimum bactericidal concentrations (MBCs) of C109 were determined for all A. baumannii strains (n = 108) by subculturing 10 µL of bacterial culture from wells, corresponding to the MIC value, and two concentrations higher than the MIC value, on MH agar plates. After 24 h of incubation in aerobic conditions at 35 °C, the lowest concentration of C109 that yielded no visible bacterial growth on MH agar plates was recorded as the MBC value [ 42 ].…”

The mechanism underlying toxicity of a venom peptide against insects reveals how ants are master at disrupting membranes

“…P17 is an immunomodulatory agonist of an orphan G protein-coupled receptor, 28 , 30 whereas M-Tb1a is a pore-forming peptide displaying antimicrobial effect against a broad spectrum of bacterial strains and cytotoxic activities by membrane permeabilization. 31 , 32 , 33 , 34 , 35 …”