Zinc oxide nanoparticles inhibits quorum sensing and virulence in Pseudomonas aeruginosa

Background: Quorum sensing inhibitionis an advanced strategy that aims to interfere with bacterial cell-to-cell communication systems (quorum sensing), which regulate virulence factors production in Pseudomonas aeruginosa, in order to overcome the globalcrisis of antimicrobial resistance.Objectives: Study the potential quorum sensing inhibitory effect of Zinc oxide (ZnO)nanoparticlesin Pseudomonas aeruginosa and the impact on production of virulence factors.Methods: Quorum sensing inhibitory effect of ZnO was evaluated by assessing its ability to reducePseudomonas aeruginosa virulence factors production; rhamnolipids, pyocyanin, pyoverdin, hemolysins, elastase and proteases. Furthermore, qRT-PCR was performed to determine ZnO inhibitory effect onQS-regulatory geneslasI, lasR,rhlI, rhlR, pqsA and pqsR that control virulence factors secretion. Moreover, mice survival test was conducted to investigate the influence of ZnO on Pseudomonas aeruginosa-induced mortality in vivo.Results: ZnO revealed a statistically significant reduction in the production of QS-controlled virulence factors rhamnolipids, pyocyanin, pyoverdin, hemolysins, elastase and proteases. Furthermore, ZnO exhibited a significant decrease in the relative expression of QS-regulatory geneslasI, lasR,rhlI, rhlR,pqsA and pqsR. Additionally, ZnO significantly reduced the pathogenesis of Pseudomonas aeruginosa in vivoConclusion: ZnO nanoparticles can be used as a quorum sensing inhibitor in Pseudomonas aeruginosa infections either as an adjuvant or alternative to conventional antimicrobials.Keywords: Pseudomonas aeruginosa, ZnO, quorum sensing, virulence inhibition

Zinc oxide nanoparticles inhibits quorum sensing and virulence in Pseudomonas aeruginosa

Background: Quorum sensing inhibitionis an advanced strategy that aims to interfere with bacterial cell-to-cell communication systems (quorum sensing), which regulate virulence factors production in Pseudomonas aeruginosa, in order to overcome the globalcrisis of antimicrobial resistance. Objectives: Study the potential quorum sensing inhibitory effect of Zinc oxide (ZnO)nanoparticlesin Pseudomonas aeruginosa and the impact on production of virulence factors. Methods: Quorum sensing inhibitory effect of ZnO was evaluated by assessing its ability to reducePseudomonas aeruginosa virulence factors production; rhamnolipids, pyocyanin, pyoverdin, hemolysins, elastase and proteases. Furthermore, qRT-PCR was performed to determine ZnO inhibitory effect onQS-regulatory geneslasI, lasR,rhlI, rhlR, pqsA and pqsR that control virulence factors secretion. Moreover, mice survival test was conducted to investigate the influence of ZnO on Pseudomonas aeruginosa-induced mortality in vivo. Results: ZnO revealed a statistically significant reduction in the production of QS-controlled virulence factors rhamnolipids, pyocyanin, pyoverdin, hemolysins, elastase and proteases. Furthermore, ZnO exhibited a significant decrease in the relative expression of QS-regulatory geneslasI, lasR,rhlI, rhlR,pqsA and pqsR. Additionally, ZnO significantly reduced the pathogenesis of Pseudomonas aeruginosa in vivo Conclusion: ZnO nanoparticles can be used as a quorum sensing inhibitor in Pseudomonas aeruginosa infections either as an adjuvant or alternative to conventional antimicrobials. DOI: https://dx.doi.org/10.4314/ahs.v19i2.28 Cite as: Saleh MM, Sadeq RA, Abdel Latif HK, Abbas HA, Askoura M. Zinc oxide nanoparticles inhibits quorum sensing and virulence in Pseudomonas aeruginosa. Afri Health Sci.2019;19(2): 2043-2055. https://dx.doi.org/10.4314/ahs.v19i2.2

Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen and one of the leading causes of nosocomial infections worldwide. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms overcoming their effects. Of these resistance mechanisms, the active efflux pumps in Pseudomonas aeruginosa that belong to the resistance nodulation division (RND) plays a very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. Beside its role against the antimicrobial agents, these pumps can extrude biocides, detergents, and other metabolic inhibitors. It is clear that efflux pumps can be targets for new antimicrobial agents. Peptidomimetic compounds such as phenylalanine arginyl β-naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic, hence, restoring its antibacterial activity. The advantage of EPIs is the difficulty to develop bacterial resistance against them, but the disadvantage is their toxic property hindering their clinical application. The structure activity relationship of these compounds showed other derivatives from PAβN that are higher in their activity with higher solubility in biological fluids and decreased toxicity level. This raises further questions on how can we compact Pseudomonas infections. Of particular importance, the recent resurgence in the use of older antibiotics such as polymyxins and probably applying stricter control measures in order to prevent their spread in clinical sittings