High-throughput screening and identification of synthetic peptides with Mycobacterium abscessus inhibitory activity

The rise in the number of antibiotic-resistant bacteria, due in part to the widespread use of antibiotics, has spawned new technological approaches for identifying novel antimicrobials with narrow specificity. Current antibiotic treatment regimens and anti-tuberculosis drugs are not effective at treating Mycobacterium abscessus; therefore, antimicrobial peptides have gained prominence as alternative antimicrobials due to their specificity towards anionic bacterial membranes, rapid action, and inability for the bacteria to develop resistance by acting against the cell membrane. Our group has developed a high-density peptide microarray consisting of 125,000 random synthetic peptides for rapid screening of antimicrobial peptides against M. abscessus. From the array screening, the peptides that interacted with the mycobacterial cell surface were synthesized and subsequent inhibitory, bactericidal, and toxicity assays were performed. Additionally, minimum inhibitory concentration assays were performed with these peptides against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in order to determine if inhibitory activity was observed against Gram-positive and Gram-negative bacteria. Six peptides, out of the 125,000 peptides screened, had inhibitory activity against M. abscessus and low toxicity (< 10%) against human red blood cells. One peptide also exhibited inhibitory activity against S. aureus and E. coli. To determine combination effects, antimicrobial synergy assays will be performed with the six peptides and clarithromycin