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PMID: 10940033 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The stringent response of Mycobacterium tuberculosis is required for long-term survival.

Journal of bacteriology ·Vol. 182 ·No. 17 ·2000-09-00 ·Pages 4889-98

Primm TP, Andersen SJ, Mizrahi V, Avarbock D, Rubin H, Barry CE

Abstract

The stringent response utilizes hyperphosphorylated guanine [(p)ppGpp] as a signaling molecule to control bacterial gene expression involved in long-term survival under starvation conditions. In gram-negative bacteria, (p)ppGpp is produced by the activity of the related RelA and SpoT proteins. Mycobacterium tuberculosis contains a single homolog of these proteins (Rel(Mtb)) and responds to nutrient starvation by producing (p)ppGpp. A rel(Mtb) knockout strain was constructed in a virulent strain of M. tuberculosis, H37Rv, by allelic replacement. The rel(Mtb) mutant displayed a significantly slower aerobic growth rate than the wild type in synthetic liquid media, whether rich or minimal. The growth rate of the wild type was equivalent to that of the mutant when citrate or phospholipid was employed as the sole carbon source. These two organisms also showed identical growth rates within a human macrophage-like cell line. These results suggest that the in vivo carbon source does not represent a stressful condition for the bacilli, since it appears to be utilized in a similar Rel(Mtb)-independent manner. In vitro growth in liquid media represents a condition that benefits from Rel(Mtb)-mediated adaptation. Long-term survival of the rel(Mtb) mutant during in vitro starvation or nutrient run out in normal media was significantly impaired compared to that in the wild type. In addition, the mutant was significantly less able to survive extended anaerobic incubation than the wild-type virulent organism. Thus, the Rel(Mtb) protein is required for long-term survival of pathogenic mycobacteria under starvation conditions.

MeSH Terms
Cell Line Culture Media Genotype Guanosine Pentaphosphate/metabolism Humans Ligases/genetics,metabolism Macrophages/microbiology Mutagenesis Mycobacterium tuberculosis/growth & development,metabolism Phenotype Time Factors
Chemicals
Culture Media Guanosine Pentaphosphate Ligases guanosine 3',5'-polyphosphate synthetases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Primm T P
Tuberculosis Research Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20852, USA.
Andersen S J
Mizrahi V
Avarbock D
Rubin H
Barry C E
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.182.17.4889-4898.2000
Published
2000-09-00
Pages
4889-98
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC111369
Subset
IM
Grants
NIAID NIH HHS · R01 AI043420 · United States
Intramural NIH HHS · Z01 AI000783-11 · United States
NIAID NIH HHS · R01-AI43420 · United States
External Links
PubMed source DOI: 10.1128/JB.182.17.4889-4898.2000 PMC Full Text View journal details
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