Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria (original) (raw)
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Methods in molecular biology (Clifton, N.J.), 2010
It is known that bacteria showing a multi-drug resistance phenotype use several mechanisms to overcome the action of antibiotics. As a result, this phenotype can be a result of several mechanisms or a combination of thereof. The main mechanisms of antibiotic resistance are: mutations in target genes (such as DNA gyrase and topoisomerase IV); over-expression of efflux pumps; changes in the cell envelope; down regulation of membrane porins, and modified lipopolysaccharide component of the outer cell membrane (in the case of Gram-negative bacteria). In addition, adaptation to the environment, such as quorum sensing and biofilm formation can also contribute to bacterial persistence. Due to the rapid emergence and spread of bacterial isolates showing resistance to several classes of antibiotics, methods that can rapidly and efficiently identify isolates whose resistance is due to active efflux have been developed. However, there is still a need for faster and more accurate methodologies. Conventional methods that evaluate bacterial efflux pump activity in liquid systems are available. However, these methods usually use common efflux pump substrates, such as ethidium bromide or radioactive antibiotics and therefore, require specialized instrumentation, which is not available in all laboratories.
Bacterial resistance to antibiotics: Active efflux and reduced uptake
Advanced Drug Delivery Reviews, 2005
Antibiotic resistance of bacterial pathogens is a fast emerging global crisis and an understanding of the underlying resistance mechanisms is paramount for design and development of new therapeutic strategies. Permeability barriers for and active efflux of drug molecules are two resistance mechanisms that have been implicated in various infectious outbreaks of antibioticresistant pathogens, suggesting that these mechanisms may be good targets for new drugs. The synergism of reduced uptake and efflux is most evident in the multiplicative action of the outer membrane permeability barrier and active efflux, which results in high-level intrinsic and/or acquired resistance in many clinically important Gram-negative bacteria. This review summarizes the current knowledge of these two important resistance mechanisms and potential strategies to overcome them. Recent advances in understanding the physical structures, function and regulation of efflux systems will facilitate exploitation of pumps as new drug targets. D
World Journal of Pharmaceutical and Life Sciences, 2018
n line with the high multidrug-resistance rates observed in bacteria and the importance of resistance mechanisms in the management of infectious diseases, the present investigation was conducted to detect with an efflux pump inhibitor (reserpine) efflux pump-expressing bacterial isolates from clinical specimens at the Laboratory of Microbiology of the Université des Montagnes Teaching Hospital. Standard disk diffusion and minimal inhibitory concentration techniques were used as recommended by CASFM, 2016. Susceptibility tests were performed on a total of 51 multidrug-resistant isolates with and without reserpine at the sub-inhibitory concentration. Out of these, 30 eventually selected as potential efflux pump-positive isolates further underwent the micro-dilution at varying concentrations of antibiotic/reserpine combinations. The minimal inhibitory concentration test values recorded with antibiotic/reserpine combination revealed improved effectiveness for Erythromycin, Tetracycline, Gentamicin, Azithromycin, Ciprofloxacin and Ofloxacin. 1024 μg/mL for reserpine was sub-inhibitory, but when it was used at 32μg / mL with Ofloxacin the MIC value recorded dropped by about 1/8 compared to the value recorded when Ofloxacin was used alone on some isolates; and about 1/2 to 1/4 with other antibiotics. Overall, 47% of isolates were positive for efflux pump expression, overwhelmed by Enterobacteriaceae (62.7%) and Micrococaceae (17.6%) and, namely Enterobacter (78%), Escherichia (57%), Staphylococcus (56 %), and Klebsiella (25%). Since organisms from these genera are most frequent etiologies of IDs further work is necessary to detect efflux pump- positive isolates in the routine process.
Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants
Microorganisms, 2016
Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics.
Efflux pumps and drug resistance in Gram-negative bacteria
Trends in Microbiology, 1994
The outer membrane of Gram-negative bacteria can only slow down the influx of lipophilic inhibitors, and so these bacteria need active efflux pumps of broad specificity to survive. Pumps such as the Escherichia coli Acr system and its homologs make Gram-negative bacteria resistant to dyes, detergents and antibiotics.
Multidrug Efflux Pumps at the Crossroad between Antibiotic Resistance and Bacterial Virulence
Frontiers in microbiology, 2016
Multidrug efflux pumps can be involved in bacterial resistance to antibiotics at different levels. Some efflux pumps are constitutively expressed at low levels and contribute to intrinsic resistance. In addition, their overexpression may allow higher levels of resistance. This overexpression can be transient, in the presence of an effector (phenotypic resistance), or constitutive when mutants in the regulatory elements of the expression of efflux pumps are selected (acquired resistance). Efflux pumps are present in all cells, from human to bacteria and are highly conserved, which indicates that they are ancient elements in the evolution of different organisms. Consequently, it has been suggested that, besides antibiotic resistance, bacterial multidrug efflux pumps would likely contribute to other relevant processes of the microbial physiology. In the current article, we discuss some specific examples of the role that efflux pumps may have in the bacterial virulence of animals' a...