PUBLICATION
Rifabutin is bactericidal against intracellular and extracellular forms of Mycobacterium abscessus
- Authors
- Johansen, M.D., Daher, W., Roquet-Banères, F., Raynaud, C., Alcaraz, M., Maurer, F.P., Kremer, L.
- ID
- ZDB-PUB-200822-5
- Date
- 2020
- Source
- Antimicrobial Agents and Chemotherapy 64(11): (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/pharmacology
- Humans
- Microbial Sensitivity Tests
- Mycobacterium Infections, Nontuberculous*/drug therapy
- Mycobacterium abscessus*
- Rifabutin/pharmacology
- Zebrafish
- PubMed
- 32816730 Full text @ Antimicrob. Agents Chemother.
Citation
Johansen, M.D., Daher, W., Roquet-Banères, F., Raynaud, C., Alcaraz, M., Maurer, F.P., Kremer, L. (2020) Rifabutin is bactericidal against intracellular and extracellular forms of Mycobacterium abscessus. Antimicrobial Agents and Chemotherapy. 64(11):.
Abstract
Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. In this context, rifabutin (RFB) has been shown to be active against M. abscessus and has raised renewed interest in using rifamycins for the treatment of M. abscessus pulmonary diseases. Herein, we compared the in vitro and in vivo activity of RFB against the smooth and rough variants of M. abscessus, differing in their susceptibility profile to several drugs and physiopathologial characteristics. While the activity of RFB is greater against rough strains than in smooth strains in vitro, suggesting a role of the glycopeptidolipid layer in susceptibility to RFB, both variants were equally susceptible to RFB inside human macrophages. RFB treatment also led to a reduction in the number and size of intracellular and extracelluar mycobacterial cords. Furthermore, RFB was highly effective in a zebrafish model of infection and protected the infected larvae from M. abscessus-induced killing. This was corroborated with a significant reduction in the overall bacterial burden, as well as decreased numbers of abscesses and cords, two major pathophysiological traits in infected zebrafish. This study indicates that RFB is active against M. abscessus both in vitro and in vivo, further supporting its potential usefulness as part of combination regimens targeting this difficult-to-treat mycobacterium.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping