Drugs with new lease of life as quorum sensing inhibitors: for combating MDR Acinetobacter baumannii infections

In this study, four FDA-approved drugs (besides azithromycin as positive QSI) were tested for potential QS inhibition against clinicalA. baumannii isolates andP. aeruginosa (PAO1) standard strain. The inhibitory effect of these drugs on virulence factors of both microbes has been investigated. The studied virulence factors include biofilm formation, twitching and swarming motilities, proteolytic enzyme production, and resistance to oxidative stress. The four tested drugs (erythromycin, levamisole, chloroquine, and propranolol) inhibited QS inChromobacterium violaceum by 84, 72, 55.1, and 37.3%, respectively. They also significantly inhibited virulence factors in both PAO1 andA. baumannii at sub-inhibitory concentrations. These findings were confirmed by qRT-PCR and mice mortality test, where tested drugs highly repressed the expression ofabaI gene and showed significantly improved mice survival rates. In addition, molecular docking studies against AbaI and AbaR proteins of QS system inA. baumannii revealed the potential inhibition of QS by tested drugs. Beside their known activities, the tested drugs could be given new life as QSIs to combatA. baumannii nosocomial infections (alone or in combination with antimicrobials).
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research