Efflux pump-mediated resistance to new beta lactam antibiotics in multidrug-resistant gram-negative bacteria

Abstract

The emergence and spread of bacteria resistant to commonly used antibiotics poses a critical threat to modern medical practice. Multiple classes of bacterial efflux pump systems play various roles in antibiotic resistance, and members of the resistance-nodulation-division (RND) transporter superfamily are among the most important determinants of efflux-mediated resistance in gram-negative bacteria. RND pumps demonstrate broad substrate specificities, facilitating extrusion of multiple chemical classes of antibiotics from the bacterial cell. Several newer beta-lactams and beta-lactam/beta-lactamase inhibitor combinations (BL/BLI) have been developed to treat infections caused by multidrug resistant bacteria. Here we review recent studies that suggest RND efflux pumps in clinically relevant gram-negative bacteria may play critical but underappreciated roles in the development of resistance to beta-lactams and novel BL/BLI combinations. Improved understanding of the genetic and structural basis of RND efflux pump-mediated resistance may identify new antibiotic targets as well as strategies to minimize the emergence of resistance. Dulanto Chiang and Dekker discuss recent work on efflux pump-mediated antibiotic resistance in gram-negative bacteria. They highlight evidence implicating RND-class efflux pumps in resistance to new broad spectrum beta lactam and beta lactam/beta lactamase inhibitor antibiotics, and implications for therapy and antibiotic development.