Antimicrobial effect of pimozide by targeting ROS-mediated killing in Staphylococcus aureus

In spite of the higher nosocomial and community-acquired infections caused by Staphylococcus aureus, emerging drug resistance is a leading cause of increased mortality and morbidity associated with the overuse of antimicrobials. It is an emergent need to find out new molecules to combat such infections. In the present study, we analyzed the antibacterial effect of pimozide (PMZ) against gram-positive and gram-negative bacterial strains, including methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) S. aureus. The growth of MSSA and MRSA was completely inhibited at concentrations of 12.5 and 100 mu g/mL, respectively, which is referred to as 1x minimum inhibitory concentration (MIC). The cell viability was completely eliminated within 90 min of PMZ treatment (2x MIC) through reactive oxygen species (ROS)-mediated killing without affecting cell membrane permeability. It suppressed alpha-hemolysin production and biofilm formation of different S. aureus strains by almost 50% at 1x MIC concentration, and was found to detach matured biofilm. PMZ treatment effectively eliminates S. aureus infection in Caenorhabditis elegans and improves its survival by 90% and is found safe to use with no hemolytic effect on human and chicken blood tissues. Taken together, it is concluded that PMZ may turn out to be an effective antibacterial for treating bacterial infections including MSSA and MRSA.

Automated summary

Despite the increase in nosocomial and community-acquired infections caused by Staphylococcus aureus, drug resistance remains a major cause of mortality and morbidity. The study analyzed the antibacterial effect of pimozide against different strains of S. aureus and found it to be effective in inhibiting growth, alpha-hemolysin production, and biofilm formation.