AUTHOR=Pearce Camron M. , Shaw Timothy D. , Podell Brendan , Jackson Mary , Henao-Tamayo Marcela , Obregon-Henao Andres , Lam Ha , Alshiraihi Ilham M. , O'Neal Wanda , Livraghi-Butrico Alessandra , Hickey Anthony J. , Meibohm Bernd , Gonzalez-Juarrero Mercedes 

TITLE=Mycobacterium abscessus pulmonary infection and associated respiratory function in cystic fibrosis-like βENaC mice

JOURNAL=Frontiers in Tuberculosis

VOLUME=2

YEAR=2024

URL=https://www.frontiersin.org/journals/tuberculosis/articles/10.3389/ftubr.2024.1473341

DOI=10.3389/ftubr.2024.1473341

ISSN=2813-7868

ABSTRACT=<sec><title>Introduction</title><p>Chronic pulmonary infection with <italic>Mycobacterium abscessus</italic> (<italic>M. abscessus</italic>) is a significant cause of morbidity and mortality in people with cystic fibrosis (CF). Developing an animal model of <italic>M. abscessus</italic> pulmonary infection, especially under CF conditions, is essential to understanding clinical pulmonary <italic>M. abscessus</italic> infection. βENaC transgenic mice are known to develop spontaneous CF-like disease characterized by airway mucus obstruction and inflammation. The aim of this study was to evaluate the suitability of βENaC mice as a preclinical model and characterize their respiratory function during <italic>M. abscessus</italic> lung infection.</p></sec><sec><title>Methods</title><p>Mice received an intrapulmonary aerosol of <italic>M. abscessus</italic> using a high-pressure syringe device (Penn-Century) for subsequent characterization of disease progression and respiratory function. Whole body unrestrained plethysmography (WBP) data was collected to monitor lung function and endpoints determined organ bacterial burden and associated pathology.</p></sec><sec><title>Results</title><p>Endpoint CFU data in the lung and spleen showed that there was no significant difference in bacterial clearance between βENaC and WT mice. WBP data showed an impairment in overall respiratory function during and after <italic>M. abscessus</italic> infection in both strains of mice. Interestingly, even in wildtype control mice, lung dysfunction persisted after bacterial clearance.</p></sec><sec><title>Discussion</title><p>Even with CF-like features, the βENaC transgenic mice cleared <italic>M. abscessus</italic> at a similar rate than WT mice, however, the associated respiratory monitoring revealed that there are long-term implications of <italic>M. abscessus</italic> lung exposure. The clear decline in respiratory function, even after <italic>M. abscessus</italic> clearance, suggests that WBP coupled animal modeling provides important insight that is relevant to disease burden and treatment efficacy. The <italic>M. abscessus</italic> clearance in the βENaC mice may help improve the fields understanding of CF-modulated immune deficiencies in <italic>M. abscessus</italic> pulmonary infection.</p></sec>