title: Mycobacterium abscessus morphotype comparison in a murine model.
abstract: Pulmonary infections with Mycobacterium abscessus (M. abscessus) are increasingly prevalent in patients with lung diseases such as cystic fibrosis. M. abscessus exists in two morphotypes, smooth and rough, but the impact of morphotype on virulence is unclear. We developed an immune competent mouse model of pulmonary M. abscessus infection and tested the differences in host inflammatory response between the morphotypes of M. abscessus. Smooth and rough morphotypes of M. abscessus were isolated from the same American Type Culture Collection strain. Wild type and cystic fibrosis mice were intratracheally inoculated with known quantities of M. abscessus suspended in fibrin plugs. At the time of sacrifice lung and splenic tissues and bronchoalveolar lavage fluid were collected and cultured. Bronchoalveolar lavage fluid was analyzed for leukocyte count, differential and cytokine expression. Pulmonary infection with M. abscessus was present at both 3 days and 14 days post-inoculation in all groups at greater levels than systemic infection. Inoculation with M. abscessus rough morphotype resulted in more bronchoalveolar lavage fluid neutrophils compared to smooth morphotype at 14 days post-inoculation in both wild type (p = 0.01) and cystic fibrosis (p<0.01) mice. Spontaneous in vivo conversion from smooth to rough morphotype occurred in 12/57 (21%) of mice. These mice trended towards greater weight loss than mice in which morphotype conversion did not occur. In the described fibrin plug model of M. abscessus infection, pulmonary infection with minimal systemic dissemination is achieved with both smooth and rough morphotypes. In this model M. abscessus rough morphotype causes a greater host inflammatory response than the smooth based on bronchoalveolar lavage fluid neutrophil levels.
authors: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Lindsay J
authors: LJ
authors: Caverly
authors: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
authors: Silvia M
authors: SM
authors: Caceres
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
authors: Cori
authors: C
authors: Fratelli
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
authors: Carrie
authors: C
authors: Happoldt
authors: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Kelley M
authors: KM
authors: Kidwell
authors: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
authors: Kenneth C
authors: KC
authors: Malcolm
authors: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
authors: Jerry A
authors: JA
authors: Nick
authors: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America; Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
authors: David P
authors: DP
authors: Nichols
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D009165:Mycobacterium Infections, Nontuberculous / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009170:Nontuberculous Mycobacteria / Q000166:cytology*; D013154:Spleen / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines