Marine-Fungi-Derived Gliotoxin Promotes Autophagy to Suppress Mycobacteria tuberculosis Infection in Macrophage

The (MTB) infection causes tuberculosis (TB) and has been a long-standing public-health threat. It is urgent that we discover novel antitubercular agents to manage the increased incidence of multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains of MTB and tackle the adverse effects o...

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Bibliographic Details
Published in:Marine drugs 2023-11, Vol.21 (12), p.616
Main Authors: Fu, Jun, Luo, Xiaowei, Lin, Miaoping, Xiao, Zimin, Huang, Lishan, Wang, Jiaxi, Zhu, Yongyan, Liu, Yonghong, Tao, Huaming
Format: Article
Language:English
Subjects:
Acids
Antitubercular agents
Autophagy
Cell growth
Cytokines
Cytotoxicity
Deep sea
Deep water
Drug development
Drug resistance
Drugs
Fungi
Gliotoxin
Health risks
Helvolic acid
Infections
Infectious diseases
Investigations
Leukemia
Macrophages
marine natural product
Microscopy
Multidrug resistance
Mycobacterium tuberculosis (MTB)
Natural products
Public health
Tuberculosis
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:The (MTB) infection causes tuberculosis (TB) and has been a long-standing public-health threat. It is urgent that we discover novel antitubercular agents to manage the increased incidence of multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains of MTB and tackle the adverse effects of the first- and second-line antitubercular drugs. We previously found that gliotoxin ( ), 12, 13-dihydroxy-fumitremorgin C ( ), and helvolic acid ( ) from the cultures of a deep-sea-derived fungus, sp. SCSIO Ind09F01, showed direct anti-TB effects. As macrophages represent the first line of the host defense system against a mycobacteria infection, here we showed that the gliotoxin exerted potent anti-tuberculosis effects in human THP-1-derived macrophages and mouse-macrophage-leukemia cell line RAW 264.7, using CFU assay and laser confocal scanning microscope analysis. Mechanistically, gliotoxin apparently increased the ratio of LC3-II/LC3-I and Atg5 expression, but did not influence macrophage polarization, IL-1β, TNF-a, IL-10 production upon MTB infection, or ROS generation. Further study revealed that 3-MA could suppress gliotoxin-promoted autophagy and restore gliotoxin-inhibited MTB infection, indicating that gliotoxin-inhibited MTB infection can be treated through autophagy in macrophages. Therefore, we propose that marine fungi-derived gliotoxin holds the promise for the development of novel drugs for TB therapy.
ISSN:1660-3397
1660-3397
DOI:10.3390/md21120616