Multidrug Efflux Pumps in Staphylococcus aureus: an Update

Abstract

The emergence of infections caused by multi- or pan-resistant bacteria in the hospital or in the community settings is an increasing health concern. Albeit there is no single resistance mechanism behind multiresistance, multidrug efflux pumps, proteins that cells use to detoxify from noxious compounds, seem to play a key role in the emergence of these multidrug resistant (MDR) bacteria. During the last decades, experimental data has established their contribution to low level resistance to antimicrobials in bacteria and their potential role in the appearance of MDR phenotypes, by the extrusion of multiple, unrelated compounds. Recent studies suggest that efflux pumps may be used by the cell as a first-line defense mechanism, avoiding the drug to reach lethal concentrations, until a stable, more efficient alteration occurs, that allows survival in the presence of that agent. In this paper we review the current knowledge on MDR efflux pumps and their intricate regulatory network in Staphylococcus aureus, a major pathogen, responsible from mild to life-threatening infections. Particular emphasis will be given to the potential role that S. aureus MDR efflux pumps, either chromosomal or plasmid-encoded, have on resistance towards different antimicrobial agents and on the selection of drug - resistant strains. We will also discuss the many questions that still remain on the role of each specific efflux pump and the need to establish appropriate methodological approaches to address all these questions.

Identification of DNA gyrase Subunit a Mutations Associated with Ciprofloxacin Resistance in Staphylococcus aureus Isolated from Nasal Infection in Kurdistan-Iran

“…The results of Hauschild demonestrate that all amino acid alteration cause fluoroquinolone resistance in gyrA were related to the Ser84->Leu and in one sample Glu88->Asp was observed (Hauschild et al, 2012). In the study of Santos Costa reported that nearly all gyrA mutations related to fluoroquinolone resistance in Staphylococcus aures was Ser84->Leu and in 3 isolates Glu88->Lys was identified (Costa et al, 2013). In the study of Rasha Ser84->Leu, two silent mutations in Ile86 and Leu103, Glu88->Lys, Gly106->Asp, Ser112->Arg in GyrA was reported (Hashem et al, 2013).…”

“…However, shortly after their introduction into the clinical practice, the first bacteria showing antibioticresistant were described. Since then the development of new antibiotics have been attend by the constant increase of antibiotic-resistant bacterial strains and different mechanisms used by bacteria to repress the fatal effect of these compounds (Costa et al, 2013). In the last decades concern about bacterial resistance to antibacterial agents because of counter availability, indiscriminate and inappropriate usage of antimicrobial agents has been arised (Neuhauser et al, 2003).…”

Prevalence of AmpC β-lactamase among Gram-negative bacteria recovered from clinical specimens in Benin City, Nigeria

“…The development of new antibiotics has been accompanied by the steady increase of antibiotic-resistant bacterial strains and the diversity of mechanisms used by bacteria to surpass the lethal effect of these compounds [2]. Many bacterial species show multi-or panresistant phenotypes and most of these multidrug resistant (MDR) bacteria can cause lifethreatening infections, and are of major concerns both in the hospital and the community [3,4].…”

Evaluation of Different Drugs in Down-Regulation of Efflux Pump Genes expression in Methicillin-Resistant <I>Staphylococcus aureus</I> Strains

“…It has been reported that efflux pumps contribute a varying degree of resistance to antibacterial agents (Costa et al, 2013). The efflux activity has been correlated with increased resistance to antibiotics.…”

“…Further, our data demonstrated that vancomycin+ceftriaxone+VRP1020 combination displayed a 4 fold reduction in MIC which might be due to synergistic activity of vancomycin+ceftriaxone+VRP1020. It has been suggested that efflux pumps belonging to the MFS, particularly NorA and NorB, utilize the proton motive force to energize the transport of antimicrobial compounds across the cell membrane, via an H+: Drug antiport mechanism (Costa et al, 2013;Martins et al, 2009).…”