Open AccessTransmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology
Author(s) -
Sheetal Verma,
Kamlesh Bhatt,
Arianne Lovey,
Rodrigo RibeiroRodrigues,
Joan E. Durbin,
Edward C. Jones-López,
Moisés Palaci,
Solange Alves Vinhas,
David Alland,
Reynaldo Dietze,
Jerrold J. Ellner,
Padmini Salgame
Publication year - 2019
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1007613
Subject(s) - mycobacterium tuberculosis , tuberculosis , lung , transmission (telecommunications) , phenotype , mycobacterium , biology , microbiology and biotechnology , lesion , nontuberculous mycobacteria , pathological , immunology , pathology , virology , medicine , gene , genetics , electrical engineering , engineering
In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respectively. We found that C3HeB/FeJ mice infected with Mtb-LT strains exhibited significantly higher bacterial burden compared to Mtb-HT strains and also developed diffused inflammatory lung pathology. In stark contrast, a significant number of mice infected with Mtb-HT strains developed caseating granulomas, a lesion type with high potential to cavitate. None of the Mtb-HT infected animals developed diffused inflammatory lung pathology. A link was observed between increased in vitro replication of Mtb-LT strains and their ability to induce significantly high lipid droplet formation in macrophages. These results support that distinct early interactions of Mtb-HT and Mtb-LT strains with macrophages and subsequent differential trajectories in pathological disease may be the mechanism underlying their transmission potential.