Poster: 58Evaluating CFTR G551D transgenic ferrets as an animal model for Mycobacteroides abscessus lung infection in CF

N. Gokanapudi; T. Gupta; K. Sakamoto; B. Ross; A. Stecenko; J. Engelhardt; F. Quinn; B. Rada

doi:10.1016/j.jcf.2026.07.090

Mycobacteroides abscessus has emerged as a multidrug resistant pathogen within the cystic fibrosis (CF) population. This bacterium exhibits morphological dimorphism: smooth (S) or rough (R) colony variants. Despite its clinical urgency, the study of M. abscessus pathogenesis and the development of novel therapeutics have been hindered by the lack of relevant animal models. Conventional murine models fail to achieve sustained bacterial colonization. To address this gap, we utilized the transgenic CFTR-G551D ferret model to establish chronic M. abscessus pulmonary infection. Ferrets are uniquely suited for CF research due to their anatomical and physiological similarities to human lungs. To evaluate the longitudinal dynamics of infection, CFTR G551D ferrets (N=11) were infected intratracheally with either smooth or rough morphotype of M. abscessus isolated from the same CF patient (Emory IRB#00042577). Baseline physiological parameters were established via the collection of pre-infection sera and nasal lavage fluid. Following a 4-week stabilization period, serial nasal wash and blood samples were collected bi-weekly to perform ELISA for the quantification of the humoral immune response (anti-M. abscessus antibodies) against heat-killed, gamma-irradiated, and whole-cell lysates of each bacterial morphotype. At the 12-week study endpoint, a comprehensive necropsy was performed to harvest nasal wash, blood, bronchoalveolar lavage, spleen, lungs, and liver. To assess systemic dissemination, tissue samples were homogenized and quantitatively cultured on selective media. To distinguish M. abscessus from microflora endemic to the G551D ferrets, recovered colonies were validated via PCR using species-specific primers. Our preliminary results of the quantitative bacterial load analysis confirmed that both morphotypes were detectable in the lungs indicating the establishment of chronic bacterial respiratory infection. Bacterial dissemination from lungs to other organs was found in CF ferrets infected with the smooth but not the rough variant. Neutrophilic infiltration was observed in the lungs of all CF ferrets (infected and uninfected). The smooth morphotype elicited a more robust humoral antibody response than the rough variant. Despite this differential immunogenicity, the systemic clinical impact remained minimal; animals infected with either morphotype demonstrated no significant body temperature fluctuations or weight loss. Our initial results indicate that the CFTR G551D ferret represents a promising translational model for characterizing M. abscessus pulmonary infections of CF. The somewhat distinct pathophysiological behaviors of the smooth and rough variants underscore the complexity of this pathogen. Ultimately, the CFTR-G551D ferret platform provides a critical foundation for the preclinical evaluation of novel antimicrobial regimens, therapeutic interventions, and personalized medicine strategies aiming to improve the clinical outcomes of M. abscessus infected CF patients.

Poster: 58Evaluating CFTR G551D transgenic ferrets as an animal model for Mycobacteroides abscessus lung infection in CF

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