Synergistic activity of a peptide mimic with quinolones and cephalosporins against Staphylococcus aureus

Abstract

Purpose : Antibiotic resistance is a global crisis. Antimicrobial peptides are being developed to provide new therapeutic options to reduce resistance. Some of these antimicrobial peptides have broad-spectrum antimicrobial activity and act rapidly on bacteria reducing its resistance. However, the half-life of peptides in the body is compromised due to proteolysis. In order to overcome this degradation, peptide mimics are developed to retain the benefits of the antimicrobial activity. This study investigated whether an antimicrobial peptide mimic could work in synergy with quinolones and cephalosporins against a multidrug-resistant strain of Staphylococcus aureus.

Methods : The antimicrobial peptide mimic 758 was used together with the first line antibiotics ciprofloxacin and ceftazidime. The minimum inhibitory concentration (MIC) of each drug was determined by the microtitre broth dilution method. Subsequently, a checkerboard assay was performed to examine the interaction between antibiotics and peptide mimic. The results were expressed as the fractional inhibitory concentration index (FICI). FICIs of ≤ 0.5 indicate synergism; 0.6-1 indicates additive effect; 1-4 - no interaction and ≥4 - antagonism.

Results : Peptide mimic 758 had a MIC of 2.5µg/ml for multidrug-resistant S. aureus strain. Compound 758 produced synergism with both ciprofloxacin and ceftazidime with a FICI of < 0.2 and 0.3 respectively. The MIC of ciprofloxacin was reduced from 2.5µg/ml to 0.15µg/ml and of the peptide mimic from 2.5µg/ml to 0.03µg/ml. The MIC of ceftazidime was reduced from 32µg/ml to 10µg/ml and of the peptide mimic from 2.5µg/ml to 0.03µg/ml.

Conclusions : The peptide mimic was able to significantly enhance the antimicrobial activity of the first-line antibiotic ciprofloxacin and third-generation cephalosporin ceftazidime. Future research will examine other strains and bacteria, as well as the mechanism of the synergy.

This is a 2021 ARVO Annual Meeting abstract.