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Global Health and Tropical Medicine

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Mycobacterial aminoglycoside acetyltransferases: A little of drug resistance, and a lot of other roles

Aminoglycoside acetyltransferases are important determinants of resistance to aminoglycoside antibiotics in most bacterial genera. In mycobacteria, however, aminoglycoside acetyltransferases contribute only partially to aminoglycoside susceptibility since they are related with low level resistance to these antibiotics (while high level aminoglycoside resistance is due to mutations in the ribosome). Instead, aminoglycoside acetyltransferases contribute to other bacterial […]
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Boldine-derived Alkaloids inhibit the activity of DNA topoisomerase I and growth of Mycobacterium tuberculosis

The spread of multidrug-resistant isolates of Mycobacterium tuberculosis requires the discovery of new drugs directed to new targets. In this study, we investigated the activity of two boldine-derived alkaloids, seconeolitsine (SCN) and N-methyl-seconeolitsine (N-SCN), against M. tuberculosis. These compounds have been shown to target DNA topoisomerase I enzyme and inhibit growth of Streptococcus pneumoniae. Both SCN and N-SCN inhibited M. tuberculosis growth at […]
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The EU approved antimalarial pyronaridine shows antitubercular activity and synergy with rifampicin, targeting RNA polymerase

The search for compounds with biological activity for many diseases is turning increasingly to drug repurposing. In this study, we have focused on the European Union-approved antimalarial pyronaridine which was found to have in vitro activity against Mycobacterium tuberculosis (MIC 5 μg/mL). In macromolecular synthesis assays, pyronaridine resulted in a severe decrease in incorporation of 14C-uracil […]
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Role of the mmr ef- flux pump in drug resistance in Mycobacterium tuberculosis

Efflux pumps are membrane proteins capable of actively transporting a broad range of substrates from the cytoplasm to the exterior of the cell. Increased efflux activity in response to drug treatment may be the first step in the development of bacterial drug resistance.
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Inhibition of drug efflux in mycobacteria with phenothiazines and other putative efflux inhibitors.

Mycobacteria are responsible for some of the oldest diseases known to man, usually associated with high morbility and mortality rates. An example is tuberculosis (TB), a major public health problem that accounts for eight million new cases each year.
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