Evaluation of nitroxyl donors’ effect on mycobacteria

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 i...

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Publicado:	2018
Materias:	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 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 Antibiotics, Antitubercular Antitubercular Agents Dose-Response Relationship, Drug Drug Interactions Microbial Viability Nitrogen Oxides
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v109_n_p35_Galizia http://hdl.handle.net/20.500.12110/paper_14729792_v109_n_p35_Galizia
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_14729792_v109_n_p35_Galizia
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spelling	paper:paper_14729792_v109_n_p35_Galizia2023-06-08T16:17:33Z Evaluation of nitroxyl donors’ effect on mycobacteria 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 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 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v109_n_p35_Galizia http://hdl.handle.net/20.500.12110/paper_14729792_v109_n_p35_Galizia
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Evaluation of nitroxyl donors’ effect on mycobacteria
topic_facet	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
description	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
title	Evaluation of nitroxyl donors’ effect on mycobacteria
title_short	Evaluation of nitroxyl donors’ effect on mycobacteria
title_full	Evaluation of nitroxyl donors’ effect on mycobacteria
title_fullStr	Evaluation of nitroxyl donors’ effect on mycobacteria
title_full_unstemmed	Evaluation of nitroxyl donors’ effect on mycobacteria
title_sort	evaluation of nitroxyl donors’ effect on mycobacteria
publishDate	2018
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v109_n_p35_Galizia http://hdl.handle.net/20.500.12110/paper_14729792_v109_n_p35_Galizia
_version_	1768541626768031744

Evaluation of nitroxyl donors’ effect on mycobacteria

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