Efflux pump inhibitor combined with ofloxacin decreases MRSA biofilm formation by regulating the gene expression of NorA and quorum sensing

Abstract

Carbonyl cyanide p-nitrophenylhydrazone (2e), an efflux pump inhibitor, displayed alone or synergistic efficacy against MRSA in vitro and in vivo through regulating the gene expression of NorA and QS system.

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

“…EPIs can also halt the secretion of virulence factors outside the bacterial cells, which are crucial for the pathogenicity of bacteria. This dual action of EPIs in reducing biofilm formation and inhibiting virulence factor secretion contributes to their potential as valuable tools in combating bacterial infections [ 211 , 212 ]. EPIs, when employed as adjuvants in combination with antibiotics, offer a promising approach to revive the activity of antibiotics that have already become ineffective, thereby restoring their diminished antimicrobial potencies [ 123 , 213 ].…”

“…EPIs can also halt the secretion of virulence factor outside the bacterial cells, which are crucial for the pathogenicity of bacteria. This dua action of EPIs in reducing biofilm formation and inhibiting virulence factor secretion con tributes to their potential as valuable tools in combating bacterial infections [211,212] EPIs, when employed as adjuvants in combination with antibiotics, offer a promising ap proach to revive the activity of antibiotics that have already become ineffective, thereby restoring their diminished antimicrobial potencies [123,213]. As an example, PAβN (Fig ure 4), a well-researched and extensively developed EPI of Mex pumps, has garnered sig nificant attention [123,[214][215][216].The application of PAβN results in a noteworthy reduc tion in the inherent susceptibility of P. aeruginosa to fluoroquinolone antibiotics, such a levofloxacin, with a substantial 8-fold increase in susceptibility.…”

Thymoquinone’ potent impairment of multidrug-resistant Staphylococcus aureus NorA efflux pump activity

“…TQ’s simultaneous actions on S. aureus cell envelopes and anti-efflux activities could be the reason for this variation in reduction. In S. aureus lineages exposed to ciprofloxacin, DNA topoisomerase mutations have been found; these changes result in increased levels of norA gene expression, which significantly enhances resistance evolvability 1 . The first basal efflux that the clinically isolated bacteria in this study displayed may have been caused by intrinsic resistance, or previous exposure to fluoroquinolone 45 (Fig.…”

“…Most of these isolates depend on the MDR efflux system (MES), which is implicated in resistance to multiple antimicrobials. To overcome the extrusion of antibiotics out of bacterial cells, an alternative combination of the antibiotics used with natural MES inhibitors is currently expanding drastically 1 . Efflux systems comprise a single-class extruding system that induces resistance to multiple classes of antibiotics.…”