In vitro and in vivo antibacterial activity of sudapyridine (WX-081) combined with other drugs against Mycobacterium abscessus

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2025-06-03 DOI:10.1016/j.tube.2025.102655

Hong Wang , Luyao Zheng , Lei Fu , Weiyan Zhang , Shaoyu Dong , Xiaoyou Chen , Yu Lu

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引用次数: 0

Abstract

The management of Mycobacterium abscessus (MAB) infection presents formidable challenges, necessitating the development of innovative antimicrobial agents and more efficacious combination therapies. The objective of this study was to investigate the in vitro, intracellular, and in vivo antibacterial activity of sudapyridine (WX-081) in combination with clarithromycin (CLR), clofazimine (CFZ), rifabutin (RFB), and linezolid (LZD) against MAB. In vitro, the interaction between WX-081 and other drugs was assessed using the checkerboard method against MAB. Synergistic or additive effects were observed when combining WX-081 with other drugs against all strains tested. The intracellular activity of WX-081 in combination with CLR, CFZ, RFB, and LZD against the MAB reference strain in J774A.1 cells was evaluated. The combination of WX-081 and CFZ or RFB exhibited potent inhibitory activity against MAB in macrophages. To evaluate pharmacodynamics, immunosuppressed BALB/c mice were infected with MAB to establish a murine model for assessing two-drug and three-drug combinations. In vivo studies demonstrated that the combination of WX-081 with CLR or both CLR and CFZ displayed antibacterial activity and significantly prevented mouse mortality. Our study demonstrates that the concurrent use of WX-081 with CLR or CLR plus CFZ holds significant promise as a clinical intervention for MAB infection.

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苏达吡啶（WX-081）联合其他药物对脓肿分枝杆菌的体外和体内抗菌活性研究

脓肿分枝杆菌（MAB）感染的管理面临着巨大的挑战，需要开发创新的抗菌药物和更有效的联合治疗。本研究旨在探讨苏达吡啶（WX-081）与克拉霉素（CLR）、氯法齐明（CFZ）、利福布汀（RFB）和利奈唑胺（LZD）联用对MAB的体外、细胞内和体内抗菌活性。体外，采用棋盘法检测WX-081与其他药物对MAB的相互作用。WX-081与其他药物联用对所有菌株均有协同或加性作用。WX-081与CLR、CFZ、RFB和LZD联合对J774A单克隆抗体参考菌株的胞内活性。评估1个细胞。WX-081与CFZ或RFB联合使用对巨噬细胞的MAB有较强的抑制作用。为了评估药效学，我们用MAB感染免疫抑制的BALB/c小鼠，建立小鼠模型来评估两药和三药联合用药。体内研究表明，WX-081与CLR或CLR与CFZ联合使用均具有抗菌活性，可显著防止小鼠死亡。我们的研究表明，WX-081与CLR或CLR + CFZ同时使用，作为单克隆抗体感染的临床干预具有重要的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.