Efflux pumps play an important role in the emergence of antibiotic-resistant Pseudomonas aeruginosa strains. The present study aimed to assess the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps in carbapenem-resistant and multidrug-resistant (MDR) P. aeruginosa strains isolated from clinical specimens between June 2019 and January 2022 in Ardabil city. The presence of efflux pump-encoding genes, i.e. mexA, mexC, mexE, and mexY, was assessed using the polymerase chain reaction (PCR) technique in 48 carbapenem-resistant and MDR P. aeruginosa strains. Real-time reverse transcription PCR was employed to evaluate the expression levels of mexA, mexC, mexE, and mexY genes. All 48 carbapenem-resistant and MDR P. aeruginosa strains harbored efflux pump-encoding genes including mexA, mexC, mexE, and mexY according to the PCR results. Overexpression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps was detected in 75% (n = 36), 83.3% (n = 40), 10.4% (n = 5) and 41.6% (n = 20) of the clinical isolates of P. aeruginosa, respectively. This study revealed that the presence and overexpression of efflux pumps are associated with the emergence of carbapenem-resistant and MDR P. aeruginosa strains. Therefore, research on efflux pump inhibitors of P. aeruginosa will be a worthwhile endeavor to increase the clinical efficiency of available antibiotics and prevent ensuing treatment failure.
Housseini B Issa K, Phan G, Broutin I. Functional mechanism of the efflux pumps transcription regulators from Pseudomonas aeruginosa based on 3D structures. Front Mol Biosci 2018; 5: 57.
Vaez H, Salehi-Abargouei A, Ghalehnoo ZR, Khademi F. Multidrug resistant Pseudomonas aeruginosa in Iran: a systematic review and metaanalysis. J Glob Infect Dis 2018; 10: 212–217.
World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. WHO;[cited 24 October 2017]. Available from: http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/.
Rodríguez-Martínez JM, Poirel L, Nordmann P. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 2009; 53: 4783–4788.
Bazghandi SA, Arzanlou M, Peeridogaheh H, Vaez H, Sahebkar A, Khademi F. Prevalence of virulence genes and drug resistance profiles of Pseudomonas aeruginosa isolated from clinical specimens. Jundishapur J Microbiol 2021; 14, e118452.
Khademi F, Ashrafi SS, Neyestani Z, Vaez H, Sahebkar A. Prevalence of class I, II and III integrons in multidrug-resistant and carbapenem-resistant Pseudomonas aeruginosa clinical isolates. Gene Rep 2021; 25, 101407.
Webber MA, Piddock LJ. The importance of efflux pumps in bacterial antibiotic resistance. J Antimicrob Chemother 2003; 51: 9–11.
Laborda P, Alcalde-Rico M, Blanco P, Martínez JL, Hernando-Amado S. Novel inducers of the expression of multidrug efflux pumps that trigger Pseudomonas aeruginosa transient antibiotic resistance. Antimicrob Agents Chemother 2019; 63: e01095–19.
Sobel ML, Neshat S, Poole K. Mutations in PA2491 (mexS) promote MexT-dependent mexEF-oprN expression and multidrug resistance in a clinical strain of Pseudomonas aeruginosa. J Bacteriol 2005; 187: 1246–1253.
Bazghandi SA, Safarirad S, Arzanlou M, Peeri-Dogaheh H, AliMohammadi H, Khademi F. Prevalence of multidrug-resistant Pseudomonas aeruginosa strains in Ardabil. J Ardabil Univ Med Sci 2021; 20: 280–286.
Safarirad S, Arzanlou M, Mohammadshahi J, Vaez H, Sahebkar A, Khademi F. Prevalence and characteristics of metallo-beta-lactamase-positive and high-risk clone ST235 Pseudomonas aeruginosa at Ardabil hospitals. Jundishapur J Microbiol 2021; 14, e115819.
Hassuna NA, Darwish MK, Sayed M, Ibrahem RA. Molecular epidemiology and mechanisms of high-level resistance to meropenem and imipenem in Pseudomonas aeruginosa. Infect Drug Resist 2020; 13: 285–293.
Linares JF, López JA, Camafeita E, Albar JP, Rojo F, Martínez JL. Overexpression of the multidrug efflux pumps MexCD-OprJ and MexEF-OprN is associated with a reduction of type III secretion in Pseudomonas aeruginosa. J Bacteriol 2005; 187: 1384–1391.
Shigemura K, Osawa K, Kato A, Tokimatsu I, Arakawa S, Shirakawa T, et al. Association of overexpression of efflux pump genes with antibiotic resistance in Pseudomonas aeruginosa strains clinically isolated from urinary tract infection patients. J Antibiot 2015; 68: 568–572.
Farra A, Islam S, Strålfors A, Sörberg M, Wretlind B. Role of outer membrane protein OprD and penicillin-binding proteins in resistance of Pseudomonas aeruginosa to imipenem and meropenem. Int J Antimicrob Agents 2008; 31: 427–433.
Al Rashed N, Joji RM, Saeed NK, Bindayna KM. Detection of overexpression of efflux pump expression in fluoroquinolone-resistant Pseudomonas aeruginosa isolates. Int J Appl Basic Med Res 2020; 10: 37–42.
Khademi F, Maarofi K, Arzanlou M, Peeri-Dogaheh H, Sahebkar A. Which missense mutations associated with DNA gyrase and topoisomerase IV are involved in Pseudomonas aeruginosa clinical isolates resistance to ciprofloxacin in Ardabil? Gene Rep 2021; 24, 101211.
Aeschlimann JR. The role of multidrug efflux pumps in the antibiotic resistance of Pseudomonas aeruginosa and other gram‐negative bacteria:insights from the Society of Infectious Diseases Pharmacists. Pharmacother J Hum Pharmacol Drug Ther 2003; 23: 916–924.
Singh M, Yau YC, Wang S, Waters V, Kumar A. MexXY efflux pump overexpression and aminoglycoside resistance in cystic fibrosis isolates of Pseudomonas aeruginosa from chronic infections. Can J Microbiol 2017; 63: 929–938.
Vaez H, Salehi-Abargouei A, Khademi F. Systematic review and meta-analysis of imipenem-resistant Pseudomonas aeruginosa prevalence in Iran. Germs 2017; 7: 86–97.
Islamieh DI, Goudarzi H, Khaledi A, Afshar D, Esmaeili D. Reduced efflux pumps expression of Pseudomonas aeruginosa with Satureja khuzistanica essential oil. Iran J Med Sci 2020; 45: 463–468.
Poole K. Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms. J Mol Microbiol Biotechnol 2001; 3: 255–264.
Oh H, Stenhoff J, Jalal S, Wretlind B. Role of efflux pumps and mutations in genes for topoisomerases II and IV in fluoroquinolone-resistant Pseudomonas aeruginosa strains. Microb Drug Resist 2003; 9: 323–328.
Pan YP, Xu YH, Wang ZX, Fang YP, Shen JL. Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa. Arch Microbiol 2016; 198: 565–571.
Pourakbari B, Yaslianifard S, Yaslianifard S, Mahmoudi S, Keshavarz-Valian S, Mamishi S. Evaluation of efflux pumps gene expression in resistant Pseudomonas aeruginosa isolates in an Iranian referral hospital. Iran J Microbiol 2016; 8: 249–256.
Lomovskaya O, Warren MS, Lee A, Galazzo J, Fronko R, Lee MA, et al. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa:novel agents for combination therapy. Antimicrob Agents Chemother 2001; 45: 105–116.