A BALB/c mouse model of Mycobacterium abscessus lung infection based on once-weekly cyclophosphamide administration

Abstract

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.