Additive Effects of N-Acetylcysteine and [R₄W₄] Combination Treatment on Mycobacterium avium

Authors

Kayvan Sasaninia, Western University of Health SciencesFollow
Iffat Hasnin Era, Western University of Health Sciences
Nezam Newman, Western University of Health Sciences
Jesse Melendez, Western University of Health Sciences
Wajiha Akif, Western University of Health Sciences
Eashan Sharma, Western University of Health Sciences
Omid Nikjeh, Western University of Health Sciences
Ira Glassman, Western University of Health Sciences
Cristián Jiménez, California State Polytechnic State University
Navya Sharma, Chapman University
Ama Xu, University of California, Riverside
Maria Lambros, Western University of Health Sciences
Miou Zhou, Western University of Health Sciences
Rakesh Tiwari, Chapman UniversityFollow
Vishwanath Venketaraman, Western University of Health SciencesFollow

Document Type

Article

Publication Date

10-24-2025

Abstract

Mycobacterium avium is an opportunistic pathogen and a leading contributor to nontuberculous mycobacterial infections in immunocompromised individuals. However, treatment duration, antibiotic toxicity, and resistance present challenges in the management of mycobacterium infections, prompting the need for novel treatment. N-acetylcysteine (NAC) has demonstrated potent antimycobacterial activity, while antimicrobial peptides such as the cyclic [R₄W₄] have shown additive effects when combined with first-line antibiotics. This study aimed to investigate the mechanism and efficacy of NAC and [R₄W₄] combination therapy against M. avium. A membrane depolarization assay was used to evaluate the effects of NAC and [R₄W₄] on M. avium cell membrane integrity. Antimycobacterial activity was assessed by treating cultures with varying concentrations of NAC, [R₄W₄], a combination, or a sham treatment. The same regimens were applied to M. avium-infected THP-1-derived macrophages to assess intracellular efficacy. NAC and [R₄W₄] each disrupted the M. avium membrane potential, with enhanced effects in combination. The combination treatment significantly reduced M. avium survival in both the culture and infected macrophages compared with NAC alone and untreated controls. [R₄W₄] and NAC also demonstrated potent antibacterial activity, while the lowest MIC and the combination of [R₄W₄] and NAC displayed additive effects, indicating an improved bacterial inhibition compared to individual treatments. These findings demonstrate the additive activity of NAC and [R₄W₄] against M. avium in vitro and suggest that combining antioxidant compounds with antimicrobial peptides may represent a promising strategy for treating mycobacterial infections.

Comments

This article was originally published in International Journal of Molecular Sciences, volume 26, issue 21, in 2025. https://doi.org/10.3390/ijms262110361

Recommended Citation

Sasaninia, K.; Era, I.H.; Newman, N.; Melendez, J.; Akif, W.; Sharma, E.; Nikjeh, O.; Glassman, I.; Jiménez, C.; Sharma, N.; et al. Additive Effects of N-Acetylcysteine and [R₄W₄] Combination Treatment on Mycobacterium avium. Int. J. Mol. Sci. 2025, 26, 10361. https://doi.org/10.3390/ijms262110361

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Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.