PUBLICATION
L-Tyrosine Limits Mycobacterial Survival in Tuberculous Granuloma
- Authors
- Gao, Y., Li, J., Guo, X., Guan, L., Wang, J., Huang, X., Wang, W., Yang, H.
- ID
- ZDB-PUB-230528-56
- Date
- 2023
- Source
- Pathogens (Basel, Switzerland) 12(5): (Journal)
- Registered Authors
- Keywords
- L-tyrosine, amino acid, mycobacterium, treatment, tuberculous granuloma, zebrafish
- MeSH Terms
- none
- PubMed
- 37242324 Full text @ Pathogens
Citation
Gao, Y., Li, J., Guo, X., Guan, L., Wang, J., Huang, X., Wang, W., Yang, H. (2023) L-Tyrosine Limits Mycobacterial Survival in Tuberculous Granuloma. Pathogens (Basel, Switzerland). 12(5):.
Abstract
Caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), tuberculosis (TB) remains a massive global public health issue. A well-known and key TB trait is caseous necrotic granuloma, which allows mycobacteria to reactivate and disseminate, thus confounding TB eradication programs. Amino acid (AA) metabolism is key to regulating immune responses in Mtb infections; however, it is currently unclear if AAs can be used to treat tuberculous granulomas. Here, we screened 20 proteinogenic AAs using a Mycobacterium marinum-infected zebrafish granuloma model. Only L-tyrosine simultaneously reduced Mycobacterium marinum (M. marinum) levels in zebrafish larvae and adults and inhibited intracellular pathogen survival levels. Mechanistically, L-tyrosine significantly upregulated interferon-γ (IFN-γ) expression in M. marinum -infected zebrafish adults but not in larvae. Using N-acetylcysteine (NAC) to inhibit reactive oxygen species (ROS), L-tyrosine appeared to inhibit Mtb intracellular survival by promoting ROS production. Thus, L-tyrosine as a non-essential AA may reduce mycobacterial survival in both macrophages and tuberculous granulomas. Our research provides a platform for the clinical development of AAs for active or latent TB patients infected with drug-sensitive or drug-resistant Mtb.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping