Non-interchangeable functions of efflux transporters of in survival under infection-associated stress.

Unlabelled: is a challenging opportunistic pathogen due to its intrinsic and acquired mechanisms of antibiotic resistance. A large repertoire of efflux transporters actively expels antibiotics, toxins, and metabolites from cells and enables growth of in diverse environments. In this study, we analyzed the roles of representative efflux pumps from the Resistance-Nodulation-Division (RND), Major Facilitator Superfamily (MFS), and Small Multidrug Resistance (SMR) families of proteins in the susceptibility of to antibiotics and bacterial growth under stresses imposed by human hosts during bacterial infections: an elevated temperature, osmotic stress, low iron, bile salts, and acidic pH.

Survival under Infection-Associated Stresses Depends on the Expression of Resistance-Nodulation-Division and Major Facilitator Superfamily Efflux Pumps.

Multidrug efflux transporters are major contributors to the antibiotic resistance of in clinical settings. Previous studies showed that these transporters are tightly integrated into the physiology of and have diverse functions. However, for many of the efflux pumps, such functions remain poorly defined.

Making sense of drug-efflux transporters in the physiological environment.

Bacterial drug-efflux transporters act synergistically with diffusion barriers of cellular membranes and other resistance mechanisms to protect cells from antibiotics and toxic metabolites. Their critical roles in clinical antibiotic and multidrug resistance are well established. In addition, a large body of evidence has been accumulated in support of their important contributions to bacterial growth and proliferation during infections.

Loss of RND-Type Multidrug Efflux Pumps Triggers Iron Starvation and Lipid A Modifications in Pseudomonas aeruginosa.

Transporters belonging to the esistance-odulation-ivision (RND) superfamily of proteins are invariably present in the genomes of Gram-negative bacteria and are largely responsible for the intrinsic antibiotic resistance of these organisms. The numbers of genes encoding RND transporters per genome vary from 1 to 16 and correlate with the environmental versatilities of bacterial species. Pseudomonas aeruginosa strain PAO1, a ubiquitous nosocomial pathogen, possesses 12 RND pumps, which are implicated in the development of clinical multidrug resistance and known to contribute to virulence, quorum sensing, and many other physiological functions.