The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 7 September 2004. doi:10.1084/jem.20040646
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 5, 647-657
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Karakousis, P. C.
Right arrow Articles by Bishai, W. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karakousis, P. C.
Right arrow Articles by Bishai, W. R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ISONIAZID
*RIFAMPIN
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Dormancy Phenotype Displayed by Extracellular Mycobacterium tuberculosis within Artificial Granulomas in Mice

Petros C. Karakousis1, Tetsuyuki Yoshimatsu1, Gyanu Lamichhane1, Samuel C. Woolwine1, Eric L. Nuermberger1, Jacques Grosset1, and William R. Bishai1,2

1 Department of Medicine, Center for Tuberculosis Research, Johns Hopkins University School of Medicine
2 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21231

Address correspondence to William R. Bishai, Dept. of Medicine, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1503 E. Jefferson St., Rm. 112, Baltimore, MD 21231. Phone: (410) 955-3507; Fax: (410) 614-8173; email: wbishai1{at}jhmi.edu

Mycobacterium tuberculosis residing within pulmonary granulomas and cavities represents an important reservoir of persistent organisms during human latent tuberculosis infection. We present a novel in vivo model of tuberculosis involving the encapsulation of bacilli in semidiffusible hollow fibers that are implanted subcutaneously into mice. Granulomatous lesions develop around these hollow fibers, and in this microenvironment, the organisms demonstrate an altered physiologic state characterized by stationary-state colony-forming unit counts and decreased metabolic activity. Moreover, these organisms show an antimicrobial susceptibility pattern similar to persistent bacilli in current models of tuberculosis chemotherapy in that they are more susceptible to the sterilizing drug, rifampin, than to the bactericidal drug isoniazid. We used this model of extracellular persistence within host granulomas to study both gene expression patterns and mutant survival patterns. Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that relMtb is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas. Interestingly, the dormancy phenotype of extracellular M. tuberculosis within host granulomas appears to be immune mediated and interferon-{gamma} dependent.

Key Words: microarrays • gene expression • antibiotics • latency • persistence

Abbreviations used in this paper: ORF, open reading frame; PVDF, polyvinylidene fluoride; RLU, relative light unit; Tn, transposon.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS