2. Academic Validation
  3. Degarelix limits the survival of mycobacteria and granuloma formation

Degarelix limits the survival of mycobacteria and granuloma formation

  • Microb Pathog. 2024 Oct 20:197:107046. doi: 10.1016/j.micpath.2024.107046.
Jiaqing Li 1,  Jing Gao 2,  Yaxian Gao 1,  Chenyue Shi 3,  Xinya Guo 2,  Huimin Huang 1,  Jie Wang 2,  Xiaochen Huang 2,  Haizhen Chen 4,  Jin Huang 5,  Wenjuan Wang 6,  Hua Yang 7
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China; School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China.
  • 2 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
  • 3 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China; Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 4 Medical Laboratory Center, Children's Hospital of Shanxi Province, Taiyuan, 030001, China.
  • 5 Department of Biochemistry and Molecular Biology, Guizhou Medical University, Guiyang, 561113, China. Electronic address: xinyuehx@163.com.
  • 6 School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China. Electronic address: reality0337@126.com.
  • 7 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China; School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China. Electronic address: yanghua97065@163.com.
PMID: 39433139 DOI: 10.1016/j.micpath.2024.107046
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.

Keywords

Degarelix; Mycobacterium; Treatment; Tuberculous granuloma; Zebrafish.

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