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Couto I

Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis.

Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype.
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From multidrug-resistant to extensively drug-resistant tuberculosis in Lisbon, Portugal: The stepwise mode of resistance acquisition

The development and transmission of extensively drug-resistant (XDR) tuberculosis (TB) constitutes a serious threat to the effective control of TB in several countries. Here, in an attempt to further elucidate the dynamics of the acquisition of resistance to second-line drugs and investigate an eventual role for eis promoter mutations in aminoglycoside resistance, we have studied a set of multidrug-resistant (MDR)/XDR-TB isolates circulating in Lisbon, Portugal.
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Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis

Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages.
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Identification of efflux pump-mediated multidrug-resistant bacteria by the ethidium bromide-agar cartwheel method.

BACKGROUND/AIM:
Bacterial multidrug resistance may be mediated by the overexpression of efflux pumps. Conventional evaluation of efflux activity using efflux pump substrates, such as ethidium bromide, requires specialised instrumentation. The agar-based method, previously reported, has been modified to evaluate as many as twelve bacterial strains and has been termed the ethidium bromide-agar cartwheel method.
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Genetic response of Salmonella enterica serotype Enteritidis to thioridazine rendering the organism resistant to the agent.

Thioridazine (TZ)-induced accumulation of the universal efflux pump substrate ethidium bromide and its subsequent efflux by Salmonella strains with various degrees of overexpressed efflux pumps takes place automatically at pH 7.4, is independent of a metabolic source, is not affected by a proton ionophore and is precluded by palmitic acid.
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Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB

Phenothiazines have their primary effects on the plasma membrane of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources, energy providing enzymes such as ATPases, and genes that regulate and code for permeability aspects of the bacterium.
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High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations

The purpose of this study was to determine the levels of isoniazid and ethionamide resistance and to identify associated mutations in endemic multidrug-resistant (MDR) strains of Mycobacterium tuberculosis from the Lisbon metropolitan area, Portugal.
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Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus.

BACKGROUND:
Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones.
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Competition between substrates of the efflux pump system of Salmonella enteritidis.

AIM:
To determine whether tetracycline competes with ethidium bromide (EB), used as substrate of efflux pumps, for extrusion by the efflux pump system of Salmonella enteritidis NCTC 13349 reference strain.
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Biocide and antimicrobial susceptibility of methicillin-resistant staphylococcal isolates from horses

The aim of this study was to evaluate the biocide and antimicrobial susceptibility of methicillin-resistant staphylococcal isolates from horses. Fourteen methicillin-resistant staphylococci (MRS) were subjected to an extensive genotype characterization, including SCCmec, dru, spa, PFGE and MLST typing. Antimicrobial susceptibility testing was performed and resistance genes were detected by PCR. Minimum bactericidal concentrations (MBCs) of four biocides [chlorhexidine acetate (CHA), benzalkonium chloride (BAC), triclosan (TCL) and glutaraldehyde (GLA)] were determined following the recommendations of document NF EN 1040.
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