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Abstract:

Nitroxyl (HNO) is a highly elusive and reactive molecule. Nitroxyl biological effects and pharmacological potential are becoming increasingly relevant. Mycobacterium tuberculosis infection needs new and more efficient drugs. Reactive Nitrogen and Oxygen Species (RNOS) are key compounds used by the immune system to fight intracellular infections, particularly Mycobacterium tuberculosis. In this context, we analyzed HNO potential to kill mycobacteria. We evaluated the viability and biological response of mycobacteria towards HNO releasing compounds. Our results show that HNO donors can affect mycobacterial growth, for both Mycobacterium smegmatis and Mycobacterium tuberculosis. The effect can be observed using a single dose or with successive additions of lower concentrations of the donor, mimicking continuous HNO exposure. When analyzing the effect of the simultaneous addition of sub-inhibitory concentrations of HNO with antibiotics commonly used for Mycobacterium tuberculosis infection treatment we observed: a positive effect on Rifampicin, Kanamycin and Delamanid activity; and a negative effect on Isoniazid and Ethambutol activity. Regarding a possible mechanism of action, based on the recently developed fluoromycobacteriophage assay, we propose that HNO acts by interfering with general mycobacterial physiological state. The results of this study positions HNO donors as potential candidates as new drugs for a new tuberculosis treatment. © 2018 Elsevier Ltd

Registro:

Documento: Artículo
Título:Evaluation of nitroxyl donors’ effect on mycobacteria
Autor:Galizia, J.; Acosta, M.P.; Urdániz, E.; Martí, M.A.; Piuri, M.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
Palabras clave:Azanone; HNO; Mycobacteria; Nitric oxide; RNOS; Tuberculosis; amitrole; antimycobacterial agent; cysteine; delamanid; ethambutol; isoniazid; kanamycin; methanesulfohydroxamic acid; n acetyl s nitrosopenicillamine; nitric oxide donor; nitroxyl; rifampicin; unclassified drug; nitrogen oxide; nitroxyl; tuberculostatic agent; antibacterial activity; Article; bacterial growth; bacterial viability; bactericidal activity; colony forming unit; controlled study; drug effect; drug exposure; drug half life; drug mechanism; minimum inhibitory concentration; mycobacteriophage; Mycobacterium smegmatis; Mycobacterium tuberculosis; nonhuman; priority journal; tuberculosis; dose response; drug interaction; growth, development and aging; metabolism; microbial viability; Mycobacterium smegmatis; Mycobacterium tuberculosis; Antibiotics, Antitubercular; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Interactions; Microbial Viability; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nitrogen Oxides
Año:2018
Volumen:109
Página de inicio:35
Página de fin:40
DOI: http://dx.doi.org/10.1016/j.tube.2018.01.006
Título revista:Tuberculosis
Título revista abreviado:Tuberculosis
ISSN:14729792
CODEN:TUBEC
CAS:amitrole, 61-82-5; cysteine, 4371-52-2, 52-89-1, 52-90-4; delamanid, 681492-22-8; ethambutol, 10054-05-4, 1070-11-7, 3577-94-4, 74-55-5; isoniazid, 54-85-3, 62229-51-0, 65979-32-0; kanamycin, 11025-66-4, 61230-38-4, 8063-07-8; n acetyl s nitrosopenicillamine, 79032-48-7; rifampicin, 13292-46-1; nitrogen oxide, 11104-93-1; Antibiotics, Antitubercular; Antitubercular Agents; Nitrogen Oxides; nitroxyl
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v109_n_p35_Galizia

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Citas:

---------- APA ----------
Galizia, J., Acosta, M.P., Urdániz, E., Martí, M.A. & Piuri, M. (2018) . Evaluation of nitroxyl donors’ effect on mycobacteria. Tuberculosis, 109, 35-40.
http://dx.doi.org/10.1016/j.tube.2018.01.006
---------- CHICAGO ----------
Galizia, J., Acosta, M.P., Urdániz, E., Martí, M.A., Piuri, M. "Evaluation of nitroxyl donors’ effect on mycobacteria" . Tuberculosis 109 (2018) : 35-40.
http://dx.doi.org/10.1016/j.tube.2018.01.006
---------- MLA ----------
Galizia, J., Acosta, M.P., Urdániz, E., Martí, M.A., Piuri, M. "Evaluation of nitroxyl donors’ effect on mycobacteria" . Tuberculosis, vol. 109, 2018, pp. 35-40.
http://dx.doi.org/10.1016/j.tube.2018.01.006
---------- VANCOUVER ----------
Galizia, J., Acosta, M.P., Urdániz, E., Martí, M.A., Piuri, M. Evaluation of nitroxyl donors’ effect on mycobacteria. Tuberculosis. 2018;109:35-40.
http://dx.doi.org/10.1016/j.tube.2018.01.006