PUBLICATION
Degarelix limits the survival of mycobacteria and granuloma formation
- Authors
- Li, J., Gao, J., Gao, Y., Shi, C., Guo, X., Huang, H., Wang, J., Huang, X., Chen, H., Huang, J., Wang, W., Yang, H.
- ID
- ZDB-PUB-241022-11
- Date
- 2024
- Source
- Microbial pathogenesis 197: 107046 (Journal)
- Registered Authors
- Keywords
- Degarelix, Mycobacterium, Treatment, Tuberculous granuloma, Zebrafish
- MeSH Terms
-
- Disease Models, Animal
- Granuloma*/drug therapy
- Granuloma*/microbiology
- Zebrafish*
- Antitubercular Agents/pharmacology
- Autophagy/drug effects
- Animals
- Mice
- Microbial Viability/drug effects
- Mycobacterium Infections, Nontuberculous/drug therapy
- Mycobacterium Infections, Nontuberculous/microbiology
- Tuberculosis/drug therapy
- Tuberculosis/microbiology
- Mycobacterium marinum*/drug effects
- Mycobacterium marinum*/pathogenicity
- Macrophages*/drug effects
- Macrophages*/microbiology
- Oligopeptides/pharmacology
- Interferon-gamma/metabolism
- Drug Repositioning
- Rifampin/pharmacology
- Rifampin/therapeutic use
- Humans
- Mycobacterium tuberculosis/drug effects
- Mycobacterium tuberculosis/genetics
- PubMed
- 39433139 Full text @ Microb. Pathog.
Citation
Li, J., Gao, J., Gao, Y., Shi, C., Guo, X., Huang, H., Wang, J., Huang, X., Chen, H., Huang, J., Wang, W., Yang, H. (2024) Degarelix limits the survival of mycobacteria and granuloma formation. Microbial pathogenesis. 197:107046.
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is a serious health hazard, characterized by tuberculous granuloma formation, which may facilitate bacterial survival. At the same time, the identification of multidrug-resistant and extremely drug-resistant Mtb strains, and the progressive accumulation of mutations in biological targets of frontline antimicrobials, has made TB treatments more difficult. Therefore, new and rapid drug development for TB is warranted. Recently, drug repurposing has received considerable attention. In this study, we applied the anticancer drug degarelix to anti-TB research and found that it inhibits mycobacteria survival and pathological damage in Mycobacterium marinum-infected zebrafish and Mtb-infected mice. Supplementation of degarelix matched the bactericidal activities of rifampicin (RFP) toward M. marinum in zebrafish. Mechanistically, degarelix significantly increased interferon (IFN)-γ levels in M. marinum-infected zebrafish. Degarelix had no direct anti-mycobacterial activity in vitro but significantly reduced the survival of H37Rv in macrophages. The effect of degarelix could be reversed by 3-methyladenine (3-MA), which inhibits the class III phosphatidylinositol (PI) 3 kinase required for autophagy initiation. However, no effect on later steps in autophagy could be detected. Our findings demonstrate the potential of degarelix on limiting mycobacterial survival and granuloma formation, which may generate novel TB therapeutics.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping