Abstract

Gram-negative bacteria pose a significant threat to global public health due to their ability to develop multidrug resistance (MDR). Among the key mechanisms driving this resistance is the action of efflux pumps, which actively transport antibiotics and other toxic compounds out of bacterial cells, reducing drug efficacy. Efflux pumps such as the Resistance-Nodulation-Division (RND), ATP-Binding Cassette (ABC), Major Facilitator Superfamily (MFS), Small Multidrug Resistance (SMR), and Multidrug and Toxic Compound Extrusion (MATE) systems contribute to intrinsic and acquired resistance in major pathogens, including Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. These pumps not only expel antibiotics but also play a role in bacterial virulence, biofilm formation, and survival in hostile environments. Addressing efflux-mediated resistance requires novel therapeutic approaches, including efflux pump inhibitors (EPIs), combination therapies, and alternative antimicrobials. Understanding the structure, function, and regulation of efflux pumps is crucial for developing effective strategies to counteract MDR Gram-negative bacterial infections and improve treatment outcomes.