Characterization of new mouse models of acute and chronicinfection for antimicrobial drug screening.

Abstract

(MAB), a rapidly growing non-tuberculous mycobacterium, is becoming increasingly recognized as a significant pathogen affecting humans. These bacteria particularly impact individuals with cystic fibrosis (CF), non-CF bronchiectasis, and compromised immune systems. Treating pulmonary infections with MAB is challenging due to the bacteria's inherent and acquired resistance to many antibiotics, including most anti-tuberculosis antibiotics. Antibiotic therapy of MAB infection is lengthy, involves multiple oral and parenteral administered drugs, induces significant toxicity, and, on many occasions, fails to cure. Consequently, developing more effective antibiotics has become a high priority. Preclinical studies to evaluate antibiotic efficacy against MAB are challenging because they fail to establish a progressive and sustained pulmonary infection in commonly used animal models. To address this issue, the course of MAB pulmonary infection was evaluated in 15 immunocompetent or deficient mouse strains. We report bacterial burden and histopathology and classify the models according to their ability to clear or sustain progressive infection beyond 28 days. We also examined the potential of these models for drug screening. Our findings provide a foundation for selecting suitable mouse models of pulmonary MAB infection for drug discovery.