Ethylenediaminetetraacetic acid: A non antibiotic adjuvant enhancing Pseudomonas aeruginosa susceptibility

Pseudomonas aeruginosa is an opportunistic bacterium which has been shown to have multi-drug resistance against fluoroquinolones, β-lactams, and aminoglycosides. In this investigation, we studied the effect of different concentrations of ethylenediaminetetraacetic acid (EDTA) on MexA-MexB-OprM efflux pump and subsequent changes in susceptibility and expression. Next, we examined, the expression of mexAB gene following treatment with half of minimum inhibitory concentration (MIC) of drugs. Our results revealed that 10 mM EDTA significantly reduced MIC of all drugs; moreover, the higher reduction (8 fold) was observed with CSE1034. MexA and MexB expression was down regulated at 2.93 and 3.21 fold, respectively with 10 mM EDTA. When the same concentration of EDTA was incorporated with drugs, the CSE1034 down regulates 5.64 and 5.94 fold expression of mexA and mexB, respectively. Moreover, meropenem treated groups exhibited 2.63 and 3.12 fold down regulation in the expression of the genes. However, treatment with piperacillin plus tazobactam, amoxicillin plus clavulanate, cefoperazone plus sulbactam and imipenem plus cilastatin did not produce changes in the expression of MexAB-OprM. Hence, CSE1034 could be one of the best choices to treat infections caused by microorganisms that overexpressed MexAB-Opr-M as compared to other drugs. Furthermore, use of EDTA disodium at appropriated concentrations can be regarded as a safe strategy to fight against the menace provided by the efflux pumps.