Antibacterial Activity of combinatorial treatments composed of transition-metal/antibiotics against Mycobacterium tuberculosis

• Published in: Scientific reports 2019-04, Vol.9 (1), p.5471, Article 5471
• Main Authors: Montelongo-Peralta, L. Z., León-Buitimea, A., Palma-Nicolás, J. P., Gonzalez-Christen, J., Morones-Ramírez, J. R.
• Format: Article
• Language: English
• Subjects: 631/326/22/1290; 631/326/2522; A549 Cells; Animals; Antibacterial activity; Antibiotics; Antitubercular Agents - pharmacology; Antitubercular Agents - toxicity; Bacteria; Bactericidal activity; Cell Proliferation; Cell Survival; Cytotoxicity; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Drug Synergism; Gram-positive bacteria; Humanities and Social Sciences; Humans; Isoniazid; Isoniazid - pharmacology; Isoniazid - toxicity; Macrophages; Metals; Mice; Microbial Sensitivity Tests; multidisciplinary; Multidrug resistance; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Public health; RAW 264.7 Cells; Rifampin; Science; Science (multidisciplinary); Silver Nitrate - pharmacology; Silver Nitrate - toxicity; Strains (organisms); Toxicity Tests; Tuberculosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-42049-5

Notwithstanding evidence that tuberculosis (TB) is declining, one of the greatest concerns to public health is the emergence and spread of multi-drug resistant strains of Mycobacterium tuberculosis (MDR-TB). MDR-TB are defined as strains which are resistant to at least isoniazid (INH) and rifampicin, the two most potent TB drugs, and their increasing incidence is a serious concern. Recently, notable efforts have been spent on research to pursue novel treatments against MDR-TB, especially on synergistic drug combinations as they have the potential to improve TB treatment. Our research group has previously reported promising synergistic antimicrobial effects between transition-metal compounds and antibiotics in Gram-negative and Gram-positive bacteria. In this work, we evaluated antimycobacterial activity of transition-metals/antibiotics combinatorial treatments against first-line drug resistant strains of Mycobacterium tuberculosis . Our data showed that INH/AgNO 3 combinatorial treatment had an additive effect (bactericidal activity) in an isoniazid-resistant clinical strain of Mycobacterium tuberculosis . Moreover, in vitro evaluation of cytotoxicity induced by both, the individual tratments of AgNO 3 and INH and the combinatorial treatment of INH/AgNO 3 in murine RAW 264.7 macrophages and human A549 lung cells; showed no toxic effects. Together, this data suggests that the INH/AgNO 3 combinatorial treatment could be used in the development of new strategies to treat resistant strains of Mycobacterium tuberculosis .