Novel circular antimicrobial peptides to combat a critical listed bacterial pathogen multi drug resistant...

Acinetobacter baumannii, acritical nosocomial pathogen, is one of the leading causes of human mortality, globally. The extraordinary genetic plasticity of A. baumannii leads to a high propensity antimicrobial resistance trait that demands urgent attention for alternative therapeutics. The current study involves synthesis and purification of two synthetic antimicrobial peptides, i.e., Cyclized melittin (CMEL) and its analog CMEL-M1, to investigate their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and mechanism of action on the ultrastructural alteration using scanning and transmission electron microscopy (SEM/TEM) against the clinical strains of multidrug-resistant A. baumannii. Mass spectrometry and Kaiser test was employed to assess the effect of cyclization and substitution of polar amino acids with basic amino acids, that created cyclic melittin and its analogue replacing threonine with arginine and lysine. By using broth dilution method, CMEL-M1 demonstrated 70 % strains had MIC value of 31.25 μg/mL, while in case of CMEL, only 20 % isolates exhibited MIC value of 31.25 μg/mL which suggested that CMEL-M1 is significantly effective against MDR- A. baumannii. Action mechanism of synthetic peptides using SEM/TEM depicted the altered cellular morphology leading to the disruption of membranes and the impairment of essential A. baumannii cellular functions. Hence, present findings clearly indicate the potential of CMEL and CMEL-M1 as therapeutic agents for the management of MDR- A. baumannii infections.