Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology | Zendy

Sheetal Verma | Zendy; Kamlesh Bhatt | Zendy; Arianne Lovey | Zendy; Rodrigo RibeiroRodrigues | Zendy; Joan E. Durbin | Zendy; Edward C. JonesLópez | Zendy; Moisés Palaci | Zendy; Solange Alves Vinhas | Zendy; David Alland | Zendy; Reynaldo Dietze | Zendy; Jerrold J. Ellner | Zendy; Padmini Salgame | Zendy

Open Access

Transmission 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. JonesLópez,

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.

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