from Keith Poole writing in Microbial Efflux Pumps: Current Research:

Antibiotic efflux systems are common in Pseudomonas aeruginosa, with chromosomally-encoded multidrug efflux systems of the Resistance Nodulation Division (RND) family, specifically MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY-OprM, of particular importance in clinical settings. Despite the broad substrate specificity of many of these, their clinical importance is limited to fluoroquinolone resistance (MexAB-OprM, MexCD-OprJ and MexEF-OprN), β-lactam resistance (MexAB-OprM, MexXY-OprM) and aminoglycoside resistance (MexXY-OprM). Expression of these systems is governed by the products of regulatory genes (mexAB-oprM: mexR, nalC, nalD; mexCD-oprJ: nfxB; mexEF-oprN: mexT; mexXY: mexZ) whose mutation is typically responsible for acquired multidrug resistance in lab and clinical isolates. With few exceptions these efflux systems are not inducible by substrate antimicrobials, consistent with antimicrobial efflux not being their intended function. Indeed, recent data highlight their induction by environmental stresses (oxidative stress, nitrosative stress, envelope stress) suggestive of a role in stress response systems in this organism. Significantly, such stresses may provide a selective pressure for antibiotic-resistant efflux mutants in vivo independent of antibiotic exposure. Given the importance of these efflux systems in intrinsic and acquired multidrug resistance in P. aeruginosa, strategies aimed at interfering with efflux-mediated resistance are being investigated.

Further reading: Microbial Efflux Pumps: Current Research

from Maria Rosalia Pasca, Silvia Buroni and Giovanna Riccardi writing in Microbial Efflux Pumps: Current Research:

It is well known that drug efflux systems contribute to the development of multi-resistance patterns in several bacterial pathogens. The selection and diffusion of Mycobacterium tuberculosis multidrug-resistant (MDR-TB), extensively drug-resistant (XDR-TB) and, more recently, totally drug-resistant (TDR) strains constitute a serious threat for tuberculosis global control. Mycobacteria, such as M. tuberculosis and Mycobacterium smegmatis, possess several putative drug efflux transporters, but their role in resistance is still a hard topic and needs to be further investigated as resistance to several drugs is usually the result of the combination of independent mutations in genes encoding either the drug target or the enzymes involved in drug activation. However, as the genetic basis of resistance to some antitubercular agents is not fully known for some clinical isolates, we cannot rule out an efflux mechanism in these strains. Several drug efflux transporters have been described in mycobacteria as responsible for resistance to aminoglycosides, chloramphenicol, fluoroquinolones, isoniazid, linezolid, rifampicin, tetracycline and other compounds but most of them were isolated in laboratory rather than in hospitals. This review highlights recent advances in our understanding of efflux-mediated drug resistance in mycobacteria, including the distribution of efflux systems in these organisms, their substrate profiles and their contribution to drug resistance.

Further reading: Microbial Efflux Pumps: Current Research

from Zhangqi Shen, Chih-Chia Su, Edward W. Yu and Qijing Zhang writing in Microbial Efflux Pumps: Current Research:

As a major food-borne pathogen, Campylobacter is frequently exposed to antibiotics used for both animal production and human medicine. The increasing prevalence of antibiotic resistant Campylobacter has become a significant concern for public health. Among all known antibiotic resistance mechanisms, multidrug efflux systems play essential roles in the intrinsic and acquired resistance to structurally diverse antimicrobials. In Campylobacter, several multidrug efflux pumps, such as CmeABC, CmeDEF, CmeG, and Acr3, have been functionally characterized, which revealed that these efflux systems not only contribute to the resistance of antimicrobials, but also play important roles in facilitating the adaptation of Campylobacter to various environments, including the intestinal tract of animal hosts. The expression of these efflux transporters are controlled by transcriptional regulators, which sense the presence of toxic substrates and modulates the transcription of these efflux genes. Inhibiting the production or function of these multidrug efflux transporters, especially CmeABC, has been evaluated using efflux pump inhibitors and antisense peptide nucleic acid (PNA), demonstrating the potential of this approach for controlling antibiotic resistance in Campylobacter. In this paper, we will review the recent advance in understanding multidrug efflux systems and discuss the development of potential intervention strategies by targeting antimicrobial efflux pumps in Campylobacter.

Further reading: Microbial Efflux Pumps: Current Research

from Yaramah M. Zalucki, Alexandra D. Mercante, Jason M. Cloward, Elizabeth A. Ohneck, Justin L. Kandler, Maira Goytia, Paul J.T. Johnson and William M. Shafer writing in Microbial Efflux Pumps: Current Research:

The export action of efflux pumps is a nearly universal mechanism used by bacteria to escape the action of toxic compounds in their environment. Antimicrobials faced by bacteria include various biocides (natural or synthetic) and classical antibiotics used in therapy of infections. Certain efflux pumps also export antimicrobials produced by their hosts and this ability likely enhances the survival of the infecting pathogen, especially during early stages of infection when mediators of innate host defense normally function to reduce the microbial load. This review is concerned with the roles of efflux pumps produced by Neisseria gonorrhoeae in contributing to its resistance to antimicrobials used in therapy of infections or those that participate in innate host defense. Specific emphasis is placed on the genetic organization, transcriptional regulation, and function of gonococcal efflux pumps. The major theme of this review is that in addition to their role in enhancing bacterial resistance to classical antibiotics and biocides, certain efflux pumps, such as those harbored by strict human pathogens like gonococci, can also influence in vivo fitness and survival of bacteria since they provide a mechanism to resist natural antimicrobials produced by their host.

Further reading: Microbial Efflux Pumps: Current Research