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Amaral L

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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Therapy Of XDR TB with thioridazine a drug beyond patent protection but eligible for patent “as new use”

Mycobacterium tuberculosis that is resistant to Isoniazid (INH) and Rifampin (Rif) and hence, multi-drug resistant (MDR) has progressed to extensive drug resistant (XDR) status. XDR strains of Mycobacterium tuberculosis (XDR Mtb) are resistant, in addition to INH and Rif, to any fluoroquinolone, streptomycin and to any of the injectable anti-TB drugs kanamycin, amikacin and capreomycin.
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Non-antibiotics reverse resistance of bacteria to antibiotics.

BACKGROUND: Most clinical isolates that exhibit a multi-drug resistant phenotype owe that resistance to over-expressed efflux pumps. Compounds that are efflux pump inhibitors (EPIs) reduce or reverse resistance to antibiotics to which the bacterial strain is initially resistant. We have evaluated non-antibiotics to reduce resistance of commonly encountered bacterial pathogens to antibiotics. MATERIALS AND METHODS: […]
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Characterization of antimicrobial resistance of Salmonella enterica food and animal isolates from Colombia: identification of a qnrB19-mediated quinolone resistance marker in two novel serovars

Ninety-three Salmonella isolates recovered from commercial foods and exotic animals in Colombia were studied. The serotypes, resistance profiles and where applicable the quinolone resistance genes were determined. Salmonella Anatum (n=14), Uganda (19), Braenderup (10) and Newport (10) were the most prevalent serovars, and resistance to tetracycline (18.3%), ampicillin (17.2%) and nalidixic acid (14%) was most […]
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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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Clinical relevance of multiple single-nucleotide polymorphisms in Pneumocystis jirovecii pneumonia: development of a multiplex PCR-single-base-extension.

Use of the old antipsychotic phenothiazine thioridazine (THZ) for therapy of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) infection is now being seriously considered.
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New patentable use of an old neuroleptic compound thioridazine to combat tuberculosis: a gene regulation perspective.

Use of the old antipsychotic phenothiazine thioridazine (THZ) for therapy of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) infection is now being seriously considered.
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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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Role of calcium in the efflux system of Escherichia coli.

Efflux of antibiotics by Escherichia coli AG100 is performed by a variety of efflux pumps, ensuring survival of the bacterium in widely diverse media. At pH 5, efflux is independent of metabolic energy during the period of time the assay is conducted; at pH 8 it is totally dependent upon metabolic energy.
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