Growing emergence of drug-resistant Pseudomonas aeruginosa and attenuation of its virulence using quorum sensing inhibitors: A critical review

Document Type : Review Article

Authors

1 Department of Pharmaceutical Science, SHALOM Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS), Naini, Prayagraj, India

2 Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad - 121 001, Haryana, India

3 Department of Chemistry, De La Salle University, Manila, Metro Manila, Philippines

Abstract

A perilous increase in the number of bacterial infections has led to developing throngs of antibiotics for increasing the quality and expectancy of life. Pseudomonas aeruginosa is becoming resistant to all known conventional antimicrobial agents thereby posing a deadly threat to the human population. Nowadays, targeting virulence traits of infectious agents is an alternative approach to antimicrobials that is gaining much popularity to fight antimicrobial resistance. Quorum sensing (QS) involves interspecies communication via a chemical signaling pathway. Under this mechanism, cells work in a concerted manner, communicate with each other with the help of signaling molecules called auto-inducers (AI). The virulence of these strains is driven by genes, whose expression is regulated by AI, which in turn acts as transcriptional activators. Moreover, the problem of antibiotic-resistance in case of infections caused by P. aeruginosa becomes more alarming among immune-compromised patients, where the infectious agents easily take over the cellular machinery of the host while hidden in the QS mediated biofilms. Inhibition of the QS circuit of P. aeruginosa by targeting various signaling pathways such as LasR, RhlR, Pqs, and QScR transcriptional proteins will help in blocking downstream signal transducers which could result in reducing the bacterial virulence. The anti-virulence agent does not pose an immediate selective pressure on growing bacterium and thus reduces the pathogenicity without harming the target species. Here, we review exclusively, the growing emergence of multi-drug resistant (MDR) P. aeruginosa and the critical literature survey of QS inhibitors with their potential application of blocking P. aeruginosa infections.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 6
June 2021
Pages 699-719

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