Extrapulmonary dissemination of mycobacterium bovis but not mycobacterium tuberculosis in a bronchoscopic rabbit model of cavitary tuberculosis

Gueno G. Nedeltchev, Tirumalai R. Raghunand, Mandeep S Jassal, Shichun Lun, Qi Jian Cheng, William Ramses Bishai

Research output: Contribution to journalArticle

Abstract

The rabbit model of tuberculosis is attractive because of its pathophysiologic resemblance to the disease in humans. Rabbits are naturally resistant to infection but may manifest cavitary lung lesions. We describe here a novel approach that utilizes presensitization and bronchoscopic inoculation to reliably produce cavities in the rabbit model. With a fixed inoculum of bacilli, we were able to reproducibly generate cavities by using Mycobacterium bovis Ravenel, M. bovis AF2122, M. bovis BCG, M. tuberculosis H37Rv, M. tuberculosis CDC1551, and the M. tuberculosis CDC1551 ΔsigC mutant. M. bovis infections generated cavitary CFU counts of 10 6 to 10 9 bacilli, while non-M. bovis species and BCG yielded CFU counts that ranged from 10 4 to 10 s bacilli. Extrapulmonary dissemination was almost exclusively noted among rabbits infected with M. bovis Ravenel and AF2122. Though all of the species yielded secondary lesions at intrapulmonary sites, M. bovis infections led to the most apparent gross pathology. Using the M. tuberculosis id and dosR gene expression patterns as molecular sentinels, we demonstrated that both the cavity wall and cavity lumen are microenvironments associated with hypoxia, upregulation of the bacterial dormancy program, and the use of host lipids for bacterial catabolism. This unique cavitary model provides a reliable animal model to study cavity pathogenesis and extrapulmonary dissemination.

Original languageEnglish (US)
Pages (from-to)598-603
Number of pages6
JournalInfection and Immunity
Volume77
Issue number2
DOIs
Publication statusPublished - Feb 2009

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ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

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