The Role of Efflux Pumps in Antibiotic Resistance of Escherichia coli
The Role of Efflux Pumps in Antibiotic Resistance of Escherichia coli
Mojtaba Asadi,1,*
1. MSc in Bacteriology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
Introduction: Antibiotic resistance has emerged as one of the most significant challenges in healthcare. Among various bacteria contributing to this issue, Escherichia coli, a naturally occurring inhabitant of the human and animal gastrointestinal tract, can lead to severe infections under certain conditions. Several mechanisms contribute to the antibiotic resistance of this organism, with efflux pumps being one of the most critical factors. Efflux pumps are membrane proteins responsible for expelling toxic compounds and antibiotics from within bacterial cells, thereby reducing the intracellular concentration of these drugs and diminishing their effectiveness.
Methods: One of the most notable efflux systems in E. coli is the AcrAB-TolC pump, which enables the bacteria to efficiently extrude a broad range of antibiotics, including tetracyclines, fluoroquinolones, and beta-lactams. This system comprises three components: AcrA and AcrB located in the inner membrane and TolC, which serves as a channel in the outer membrane. It utilizes the proton motive force (PMF) for energy, actively pumping antibiotics out of the cell. To investigate the role of efflux pumps in the antibiotic resistance of Escherichia coli, various laboratory and molecular techniques were employed, as 1- Determination of Minimum Inhibitory Concentration (MIC): The MIC was assessed in the presence and absence of efflux pump inhibitors. A reduction in MIC in the presence of these inhibitors would indicate a significant involvement of efflux pumps in antibiotic resistance. 2- The expression levels of the genes AcrA, AcrB, and TolC, which are associated with efflux pumps, were quantified using PCR techniques. An increase in the expression of these genes typically corresponds to a higher level of antibiotic resistance. 3- The sensitivity of the bacteria to antibiotics was evaluated using the Disk Diffusion Test in the presence of efflux pump inhibitors. This testing can provide insights into the role of efflux pumps in mediating antibiotic resistance.
Results: Efflux pumps not only confer resistance to specific antibiotics but also facilitate multi-drug resistance due to the non-specific nature of certain pumps. For instance, the AcrAB-TolC system can effectively expel various classes of antibiotics, allowing E. coli to develop resistance against multiple pharmacological agents. The increased activity of efflux pumps can lead to reduced concentration of administered antibiotics to levels insufficient for bacterial eradication. The regulation of efflux pump expression is controlled by complex mechanisms involving multiple regulatory factors, such as MarA, SoxS, and Rob, which play critical roles in the induction of these systems. Extensive efforts are underway to combat resistance mediated by efflux pumps. One promising strategy is the use of efflux pump inhibitors.
Conclusion: The combination of antibiotics with these inhibitors is currently under investigation and may contribute to reducing drug resistance in E. coli. In summary, efflux pumps are key players in the development of antibiotic resistance in E. coli, significantly impacting the efficacy of antibacterial treatments. A better understanding of these systems and the development of novel approaches to mitigate their activity can potentially enhance strategies to control antibiotic resistance and improve therapeutic outcomes.