Resistance in gram-negative bacilli: the emergence of RND efflux pumps

The rise of antimicrobial resistance has been a significant problem in recent decades, decreasing the effectiveness of antibiotics and making the treatment of infections increasingly difficult. This phenomenon can be acquired through various mechanisms, with antibiotic efflux mediated by proteins known as efflux pumps being one of the most important. Currently, these protein systems are classified into six major families. The resistance-nodulation-cell division (RND) superfamily significantly contributes to multidrug resistance, particularly against tetracyclines, aminoglycosides, β-lactams, macrolides, and fluoroquinolones. This is largely due to its broad substrate specificity and widespread distribution among Gram-negative bacteria, including members of the Enterobacterales order and non-fermenting bacilli, with pumps connecting the inner and outer membranes throughout the periplasm and forming complexes that efficiently expel antibiotics from the cell. Given the importance of these efflux proteins in bacterial resistance and physiology, several authors have sought to characterize and report new isolates and emerging pumps worldwide, as awareness of low antimicrobial susceptibility and its contributors can aid decision-making for infection control. Therefore, this study aimed to gather and analyze available data in the literature regarding the functioning and emergence of efflux pumps belonging to the RND family and highlight those with greater clinical importance, along with previously identified inhibitors to combat this resistance mechanism.