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

作者信息

Rimal Binayak, Panthi Chandra M, Howe Ruth A, Lamichhane Gyanu

机构信息

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.

出版信息

Dis Model Mech. 2025 Sep 1;18(9). doi: 10.1242/dmm.052310. Epub 2025 May 29.


DOI:10.1242/dmm.052310
PMID:40289546
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.

摘要

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本文引用的文献

[1]
Oral oxaborole MRX-5 exhibits efficacy against pulmonary in mouse.

Antimicrob Agents Chemother. 2024-11-6

[2]
Efficacy of epetraborole against in a mouse model of lung infection.

Antimicrob Agents Chemother. 2024-8-7

[3]
An optimized cyclophosphamide-treated mouse model of pulmonary infection.

Antimicrob Agents Chemother. 2024-8-7

[4]
Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations.

Tuberculosis (Edinb). 2024-7

[5]
Epidemiology of Mycobacterium abscessus.

Clin Microbiol Infect. 2024-6

[6]
Efficacy of Omadacycline-Containing Regimen in a Mouse Model of Pulmonary Mycobacteroides abscessus Disease.

mSphere. 2023-4-20

[7]
Preclinical murine models to study lung infection with Mycobacterium abscessus complex.

Tuberculosis (Edinb). 2023-1

[8]
Microbiological profile, preclinical pharmacokinetics and efficacy of CRS0393, a novel antimycobacterial agent targeting MmpL3.

Tuberculosis (Edinb). 2023-1

[9]
Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review.

Int J Infect Dis. 2022-12

[10]
Clofazimine as a comparator for preclinical efficacy evaluations of experimental therapeutics against pulmonary M. abscessus infection in mice.

Tuberculosis (Edinb). 2022-12

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