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Ramos J

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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The in vitro activity of products formed from exposure of chlorpromazine to a 266nm laser beam against species of mycobacteria of human interest

Chlorpromazine (CPZ) was exposed to a 266 nm laser beam for different periods of time ranging from minutes to 24 h. At intervals, the products from irradiation were evaluated by thin-layer chromatography (TLC) and evaluated for their activity against mycobacteria of human interest (Mycobacterium tuberculosis, M. avium, M. intracellulare and their corresponding reference strains or clinical isolates).
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Ethidium bromide transport across Mycobacterium smegmatis cell-wall: correlation with antibiotic resistance.

BACKGROUND:
Active efflux systems and reduced cell-wall permeability are considered to be the main causes of mycobacterial intrinsic resistance to many antimicrobials. In this study, we have compared the Mycobacterium smegmatis wild-type strain mc2155 with knockout mutants for porins MspA (the main porin of M. smegmatis) and MspC, the efflux pump LfrA (the main efflux pump system of M. smegmatis) and its repressor LfrR for their ability to transport ethidium bromide (EtBr) on a real-time basis.
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Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity

The disturbing emergence of multidrug-resistant strains of Mycobacterium tuberculosis(Mtb) has been driving the scientific community to urgently search for new and efficient antitubercular drugs. Despite the various drugs currently under evaluation, isoniazid is still the key and most effective component in all multi-therapeutic regimens recommended by the WHO. This paper describes the QSAR-oriented design, synthesis and in vitro antitubercular activity of several potent isoniazid derivatives (isonicotinoyl hydrazones and isonicotinoyl hydrazides) against H37Rv and two resistant Mtb strains.
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