Abstract
BACKGROUND: Pseudomonas aeruginosa is a Gram-negative pathogen frequently responsible for nosocomial infections and a significant problem in intensive care units. P. aeruginosa, as an opportunistic pathogen, increases mortality risks for severely wounded and immunocompromised individuals. The inherent drug-resistance of P. aeruginosa now requires novel therapeutics with multiple mechanisms that will offer lasting potency in the post-antibiotic era. Synthetic antimicrobial peptides (AMPs) are ideal, as their multiple modes of action slow resistance development. In this study, we investigated the potential of novel proprietary AMP OB1111 to effectively treat P. aeruginosa under standard antimicrobial susceptibility testing (AST) and host-mimicking conditions, in planktonic and biofilm states, and at sublethal and lethal concentrations. RESULTS: The highly virulent PA14 and moderately virulent PAO1 reference strains were used in these studies. OB1111 effectively displayed inhibitory and bactericidal activity against both strains under AST conditions in planktonic and biofilm states. OB1111 demonstrated anti-virulence activity under host-mimicking conditions by reducing pyoverdine production and early biofilm attachment at sublethal concentrations. Under AST conditions, sublethal doses of OB1111 gradually reduced planktonic PA14 and PAO1 growth but showed less efficacy against biofilms. Additionally, PAO1 biofilms showed reduced susceptibility to OB1111 in comparison to PA14 biofilms at sublethal concentrations. Of significance, scanning electron microscopy revealed that OB1111 effectively deformed and disintegrated PA14 and PAO1 membranes in both the planktonic and biofilm states. CONCLUSIONS: OB1111 successfully demonstrated the capacity to combat P. aeruginosa as an anti-planktonic, anti-biofilm, and anti-virulence agent. Future studies should further examine specific mechanisms of action against PA14 and PAO1, along with testing against clinical isolates in AST and host-mimicking conditions.