2. Academic Validation
  3. N-Acetylcysteine as a Host-Directed Therapy Against Clarithromycin-Resistant Mycobacterium abscessus

N-Acetylcysteine as a Host-Directed Therapy Against Clarithromycin-Resistant Mycobacterium abscessus

  • Pathogens. 2025 Mar 21;14(4):302. doi: 10.3390/pathogens14040302.
Shuqi Yang 1 2,  Ying Zhang 1 2,  Jinchuan Xu 1 3,  Zhenyan Chen 1 2,  Yang Ren 1 2,  Yujiao Long 1 2,  Xuejiao Huang 1 2,  Juanxi Liu 1 2,  Huan Huang 1 2,  Shiqi Xie 1 2,  Ruiqing Ma 1 2,  Yajuan Dong 1 2,  Xiaoyong Fan 1 2 4,  Zhidong Hu 1 2,  Feng Li 1 2 4
Affiliations

Affiliations

  • 1 Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China.
  • 2 Tuberculosis Research Center, Shanghai Public Health Clinical Center, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China.
  • 3 Central Laboratory of Clinical Laboratory Diagnosis, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
  • 4 Shanghai Institute of Infectious Diseases and Biosecurity, 138 Medical College Road, Xuhui District, Shanghai 200032, China.
PMID: 40333083 DOI: 10.3390/pathogens14040302
Abstract

(1) Background: The treatment of Mycobacterium abscessus (M. abscessus) infections resistant to clarithromycin (CLR) is highly challenging. Traditional non-tuberculous mycobacteria (NTM) chemotherapy may disturb the immune homeostasis of the host by increasing oxidative stress; therefore, host-directed immunotherapy is an alternative option for infections caused by M. abscessus. (2) Method: A clinical isolate of CLR-resistant M. abscessus was screened, and then the therapeutic effects of N-acetylcysteine (NAC) against CLR-resistant M. abscessus Infection were evaluated in Tohoku Hospital Pediatrics-1 (THP-1) cells and murine models. RNA Sequencing and Western blot were used to profile the protective immune responses induced by NAC. The contribution of candidate signaling pathways was confirmed by the corresponding inhibitor and agonist. (3) Results: NAC immunotherapy led to a significant reduction in Bacterial loads both in THP-1 cells and murine Infection models, which was associated with enhanced antioxidant effects and downregulation of Apoptosis signal-regulating kinase 1 (ASK1)-mitogen-activated protein ki-nase/extracellular signal-regulated kinase 3/6 (MKK3/6)-p38 mitogen-activated protein kinase (MAPK)-mediated inflammatory immune responses. The inhibitor of p38 signaling mimicked the protective effect of NAC, while the agonist attenuated it, suggesting that the p38 pathway is crucial in NAC-mediated immune protection against M. abscessus Infection. (4) Conclusion: Our study suggests that NAC could be used as a host-directed therapy agent against drug-resistant M. abscessus Infection.

Keywords

Mycobacterium abscessus; N-acetylcysteine; clarithromycin; host-directed therapy; immune regulation; non-tuberculous mycobacteria.

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