Rimal Binayak, Panthi Chandra M, Howe Ruth A, Lamichhane Gyanu
Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Center for Nontuberculous Mycobacteria and Bronchiectasis, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Dis Model Mech. 2025 Sep 1;18(9). doi: 10.1242/dmm.052310. Epub 2025 May 29.
Mycobacterium abscessus is a fast-growing non-tuberculous mycobacterium that can cause chronic lung disease leading to rapid decline in lung function. There are no FDA-approved therapies for this disease. To support the development of new treatments, an animal model of M. abscessus lung infection that is simple to implement and requires minimal resources is crucial to encourage broad adoption. We present a mouse model using the immunocompetent BALB/c strain, which is both widely available and cost effective. Since BALB/c mice naturally clear M. abscessus infections, immunosuppression is necessary to sustain bacterial growth in the lungs. Once-weekly intraperitoneal injections of the immunosuppressant cyclophosphamide at 250 mg/kg successfully induced proliferation of M. abscessus during the acute phase, followed by stabilization characteristic of chronic infection. This model demonstrated the efficacy of imipenem - an antibiotic commonly used in clinical settings - by significantly reducing bacterial burdens, mirroring their effects in human cases. However, clofazimine, which is also used to treat this disease, was bacteriostatic. This cost-effective and accessible mouse model is suitable for diverse laboratory environments and provides a valuable tool for preclinical evaluation of treatments for M. abscessus lung disease.
脓肿分枝杆菌是一种生长迅速的非结核分枝杆菌，可导致慢性肺部疾病，致使肺功能迅速下降。目前尚无美国食品药品监督管理局（FDA）批准的针对该疾病的疗法。为支持新治疗方法的研发，一种易于实施且所需资源最少的脓肿分枝杆菌肺部感染动物模型对于促进广泛应用至关重要。我们展示了一种使用具有免疫活性的BALB/c品系小鼠的模型，该品系小鼠广泛可得且成本效益高。由于BALB/c小鼠能自然清除脓肿分枝杆菌感染，因此需要进行免疫抑制以维持肺部细菌生长。每周一次腹腔注射250 mg/kg的免疫抑制剂环磷酰胺，在急性期成功诱导了脓肿分枝杆菌的增殖，随后呈现出慢性感染的稳定特征。该模型通过显著降低细菌载量，证明了临床常用抗生素亚胺培南的疗效，这与该药物在人类病例中的效果相符。然而，同样用于治疗该疾病的氯法齐明具有抑菌作用。这种具有成本效益且易于获取的小鼠模型适用于各种实验室环境，为脓肿分枝杆菌肺部疾病治疗的临床前评估提供了有价值的工具。
