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Evaluation of nitroxyl donors' effect on mycobacteria
Jordana Galizia1, Mariano Prado Acosta1, Estefanía Urdániz1
1Departamento 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.
Tuberculosis (Edinburgh, Scotland)
|March 22, 2018
Summary
Nitroxyl (HNO) donors show potential for treating tuberculosis by impacting mycobacterial growth. HNO enhances some antibiotics while reducing others, suggesting a novel therapeutic approach for Mycobacterium tuberculosis infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Nitroxyl (HNO) is a reactive molecule with emerging biological significance.
- Mycobacterium tuberculosis infection requires novel therapeutic strategies.
- Reactive Nitrogen and Oxygen Species (RNOS) play a role in combating intracellular infections.
Purpose of the Study:
- To investigate the potential of nitroxyl (HNO) donors in combating mycobacteria.
- To evaluate the effects of HNO on the viability and growth of Mycobacterium species.
- To explore the synergistic or antagonistic effects of HNO with existing tuberculosis drugs.
Main Methods:
- Assessing mycobacterial viability and growth in response to HNO releasing compounds.
- Testing single and multiple low-dose exposures to HNO donors.
- Evaluating the combined effects of sub-inhibitory HNO concentrations with standard tuberculosis antibiotics (Rifampicin, Kanamycin, Delamanid, Isoniazid, Ethambutol).
- Utilizing a fluoromycobacteriophage assay to probe the mechanism of action.
Main Results:
- HNO donors significantly affected the growth of both Mycobacterium smegmatis and Mycobacterium tuberculosis.
- Continuous or single-dose HNO exposure demonstrated antimicrobial effects.
- HNO enhanced the activity of Rifampicin, Kanamycin, and Delamanid against M. tuberculosis.
- HNO reduced the efficacy of Isoniazid and Ethambutol.
Conclusions:
- Nitroxyl donors exhibit direct antimycobacterial activity.
- HNO influences the efficacy of current tuberculosis treatments, with varied effects on different antibiotics.
- HNO appears to disrupt the general physiological state of mycobacteria.
- HNO donors represent promising candidates for developing new tuberculosis therapeutics.