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Article

Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria

1
Department of Microbiology, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
2
Microbiology Unit, Clinical University Hospital Lozano Blesa, 50009 Zaragoza, Spain
3
State University of New York Upstate Medical Center, Syracuse, NY 13210, USA
4
Department of Microbiology and Immunology, Centre for Tuberculosis Research, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
5
Institute for Infection & Immunity, St. George’s University of London, London SW17 0RE, UK
6
Research & Development Agency of Aragón (ARAID) Foundation, 50018 Zaragoza, Spain
7
CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editors: Jorge H. Leitão and Luis G. Alves
Antibiotics 2021, 10(4), 381; https://doi.org/10.3390/antibiotics10040381
Received: 19 March 2021 / Revised: 29 March 2021 / Accepted: 31 March 2021 / Published: 3 April 2021
Infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide, resulting in a new global health concern. NTM treatment is complex and requires combinations of several drugs for lengthy periods. In spite of this, NTM disease is often associated with poor treatment outcomes. The anti-parasitic family of macrocyclic lactones (ML) (divided in two subfamilies: avermectins and milbemycins) was previously described as having activity against mycobacteria, including Mycobacterium tuberculosis, Mycobacterium ulcerans, and Mycobacterium marinum, among others. Here, we aimed to characterize the in vitro anti-mycobacterial activity of ML against a wide range of NTM species, including Mycobacteroides abscessus. For this, Minimum Inhibitory Concentration (MIC) values of eight ML were determined against 80 strains belonging to nine different NTM species. Macrocyclic lactones showed variable ranges of anti-mycobacterial activity that were compound and species-dependent. Milbemycin oxime was the most active compound, displaying broad-spectrum activity with MIC lower than 8 mg/L. Time kill assays confirmed MIC data and showed bactericidal and sterilizing activity of some compounds. Macrocyclic lactones are available in many formulations and have been extensively used in veterinary and human medicine with suitable pharmacokinetics and safety properties. This information could be exploited to explore repurposing of anti-helminthics for NTM therapy. View Full-Text
Keywords: avermectins; nontuberculous mycobacteria; Mycobacteroides abscessus; selamectin; milbemycin oxime; repurposing avermectins; nontuberculous mycobacteria; Mycobacteroides abscessus; selamectin; milbemycin oxime; repurposing
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MDPI and ACS Style

Muñoz-Muñoz, L.; Shoen, C.; Sweet, G.; Vitoria, A.; Bull, T.J.; Cynamon, M.; Thompson, C.J.; Ramón-García, S. Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria. Antibiotics 2021, 10, 381. https://doi.org/10.3390/antibiotics10040381

AMA Style

Muñoz-Muñoz L, Shoen C, Sweet G, Vitoria A, Bull TJ, Cynamon M, Thompson CJ, Ramón-García S. Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria. Antibiotics. 2021; 10(4):381. https://doi.org/10.3390/antibiotics10040381

Chicago/Turabian Style

Muñoz-Muñoz, Lara, Carolyn Shoen, Gaye Sweet, Asunción Vitoria, Tim J. Bull, Michael Cynamon, Charles J. Thompson, and Santiago Ramón-García. 2021. "Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria" Antibiotics 10, no. 4: 381. https://doi.org/10.3390/antibiotics10040381

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