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PMID: 17384189 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Mycobacterial bacilli are metabolically active during chronic tuberculosis in murine lungs: insights from genome-wide transcriptional profiling.

Journal of bacteriology ·Vol. 189 ·No. 11 ·2007-06-00 ·Pages 4265-74

Talaat AM, Ward SK, Wu CW, Rondon E, Tavano C, Bannantine JP, Lyons R, Johnston SA

Abstract

Chronic tuberculosis represents a major health problem for one-third of the world's population today. A key question relevant to chronic tuberculosis is the physiological status of Mycobacterium tuberculosis during this important stage of infection. To examine the molecular bases of chronic tuberculosis and the role of host immunity in mycobacterial growth, we determined the mycobacterial transcriptional profiles during chronic and reactivation phases of murine tuberculosis using in vivo microarray analysis (IVMA). Following 28 days of aerosol infection, mycobacterial counts remained stable, although the bacilli were metabolically active with a 50% active transcriptome. The expression of genes involved in lipid and carbohydrate pathways was significantly enriched during the middle stage of chronic tuberculosis, suggesting a nutrient-rich microenvironment. A total of 137 genes were significantly regulated in mid-chronic tuberculosis (45 and 60 days) compared to an early stage (14 days) of infection. Additional sets of genes, including the virulence regulator virS, were up-regulated during the reactivation stage, indicating their possible roles in mycobacterial resurgence. Interestingly, a set of potential transcriptional regulators was significantly induced at the late stage of chronic tuberculosis. Bioinformatic analysis identified a large number of genes that could be regulated by one of the potential transcriptional regulators encoded by rv0348, including the sigF operon. Taken together, IVMA provided a better definition of the transcriptional machinery activated during chronic and reactivation stages of tuberculosis and identified a novel transcriptional regulator. A similar approach can be adopted to study key stages of intracellular pathogens.

MeSH Terms
Animals Bacterial Proteins/genetics,metabolism Chronic Disease Cluster Analysis Electrophoretic Mobility Shift Assay Gene Expression Profiling Gene Expression Regulation, Bacterial Genome, Bacterial Mice Mice, Inbred BALB C Mycobacterium tuberculosis/genetics,growth & development,metabolism Oligonucleotide Array Sequence Analysis Transcription, Genetic Tuberculosis, Pulmonary/microbiology,pathology
Chemicals
Bacterial Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Talaat Adel M
Laboratory of Bacterial Genomics, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706-1581, USA. [email protected]
Ward Sarah K
Wu Chia-Wei
Rondon Elizabeth
Tavano Christine
Bannantine John P
Lyons Rick
Johnston Stephen A
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.00011-07
Email
[email protected]
Published
2007-06-00
Epub
2007-00-23
Pages
4265-74
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC1913421
Subset
IM
Grants
NIAID NIH HHS · R21 AI066235 · United States
NIGMS NIH HHS · T32 GM007215 · United States
NIAID NIH HHS · R21AI066235 · United States
NIGMS NIH HHS · T32GM007215 · United States
External Links
PubMed source DOI: 10.1128/JB.00011-07 PMC Full Text View journal details
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