Efflux MexAB-Mediated Resistance in P. aeruginosa Isolated from Patients with Healthcare Associated Infections

Abstract

Today, one of the most important challenges for physicians is the adequate treatment of infections due to multidrug resistant organism (MDR). Pseudomonas aeruginosa is considered an opportunistic organism causing different types of healthcare associated infections (HAIs). We aimed to investigate the MDR and pandrug resistance (PDR) rate in P. aeruginosa in our region and detect efflux-pump mexAB genes and the proposed binding interactions of five different categories of antimicrobial agents with the mexB pump. A total of 180 non-duplicated P. aeruginosa strains were isolated from patients with HAIs in the Suez Canal University Hospital. Phenotypically, minimum inhibitory concentration (MIC) was done for all MDR and PDR strains before and after addition of efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Molecular detection of mexA and mexB genes was done by using polymerase chain reaction (PCR). Most of the isolated strains (126 strains) were MDR (70%); only 10 samples (5.5%) were PDR. MexA and mexB genes were detected in 88.2% (120 strains) and 70.5% (96 strains) of stains, respectively. All PDR strains (10 stains) carried both mexA and mexB genes. Efflux mexAB genes were detected in all MDR and PDR strains (136 strains). Molecular modeling studies were performed to investigate the modes of intermolecular binding interactions between the antimicrobial agents and mexB key amino acids that resulted in MDR and PDR. The current study reported high prevalence of MDR and PDR P. aeruginosa in patients with HAIs in the Suez Canal University Hospitals.

Effect of Titanium Dioxide Nanoparticles on the Expression of Efflux Pump and Quorum-Sensing Genes in MDR Pseudomonas aeruginosa Isolates

“…In the present study, twenty-five P. aeruginosa isolates recovered from different clinical specimens were considered as multidrug resistant isolates, as these strains were non-susceptible (resistant or intermediate) to one antimicrobial agent in three or more different antimicrobial classes [ 15 ].…”

“…These results suggested that efflux pumps are the main mechanism of resistance in the tested isolates. Many studies from Egypt reported that the efflux pump was the main cause of the decrease in ciprofloxacin and meropenem resistance, as the MICs of ciprofloxacin and meropenem significantly reduced after the addition of CCCP [ 15 , 31 ].…”

Expression of Mex AB-Opr M efflux pump system and meropenem resistance in Pseudomonas aeruginosa isolated from surgical intensive care unit

“…Pseudomonas aeruginosa (P. aeruginosa) is one of the important pathogens reported in community and healthcare-associated infections (HAIs). Emergence of pan drug-resistant (PDR) and multidrug-resistant strains (MDR) is considered a significant public health issue not only impairing the antibacterial agents' effectiveness but also wasting the efforts for developing new drugs [1].…”

Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

“…In 2007, an Algerian study on 199 strains demonstrated an overproduction of MexAB-OprM in 24% of strains [ 103 ]. Currently, depending on the studies, overexpression of mexA and mexB measures between 50 to 88% in clinical P. aeruginosa strains [ 104 , 105 ]. A study investigated 147 P. aeruginosa isolates from 89 clinical samples from various hospital countries (Australia, USA, and the Netherlands), 20 veterinary and 38 wastewater origins collected from 2012 to 2017 [ 106 ].…”