Background: The over use of current antibiotics and low discovery rate of the new ones are
leading to rapid development of multidrug-resistant pathogens worldwide. Antimicrobial peptides have
shown promising results against multidrug-resistant bacteria.
Objective: To investigate the antimicrobial activity of a new ultrashort hexapeptide (OW).
Methods: The OW hexapeptide was designed and tested against different strains of bacteria with different
levels of sensitivity. Bacterial susceptibility assays were performed according to the guidelines
of the Clinical and Laboratory Institute (CLSI). The synergistic studies were then conducted using the
Checkerboard assay. This was followed by checking the hemolytic effect of the hexapeptide against
human blood cells and Human Embryonic Kidney cell line (HEK293). Finally, the antibiofilm activities
of the hexapeptide were studied using the Biofilm Calgary method.
Results: Synergistic assays showed that OW has synergistic effects with antibiotics of different mechanisms
of action. It showed an outstanding synergism with Rifampicin against methicillin resistant
Staphylococcus aureus; ΣFIC value was 0.37, and the MIC value of Rifampicin was decreased by
85%. OW peptide also displayed an excellent synergism with Ampicillin against multidrug-resistant
Pseudomonas aeruginosa, with ΣFIC value of less than 0.38 and a reduction of more than 96% in the
MIC value of Ampicillin.
Conclusion: This study introduced a new ultrashort peptide (OW) with promising antimicrobial potential
in the management of drug-resistant infectious diseases as a single agent or in combination with
commonly used antibiotics. Further studies are needed to investigate the exact mechanism of action of