Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling.

作者: Joanna C. Betts , Pauline T. Lukey , Linda C. Robb , Ruth A. McAdam , Ken Duncan

DOI: 10.1046/J.1365-2958.2002.02779.X

关键词:

摘要: The search for new TB drugs that rapidly and effectively sterilize the tissues are thus able to shorten duration of chemotherapy from current 6 months has been hampered by a lack understanding metabolism bacterium when in 'persistent' or latent form. Little is known about condition which bacilli survive, although laboratory models have shown Mycobacterium tuberculosis can exist non-growing, drug-resistant state may mimic persistence vivo. Using nutrient starvation, we established model M. arrests growth, decreases its respiration rate resistant isoniazid, rifampicin metronidazole. We used microarray proteome analysis investigate response starvation. Proteome 6-week-starved cultures revealed induction several proteins. Microarray enabled us monitor gene expression during adaptation starvation confirmed changes seen at protein level. This provided evidence slowdown transcription apparatus, energy metabolism, lipid biosynthesis cell division addition stringent other genes play role maintaining long-term survival within host. Thus, generated with agents active against persistent number potential targets expressed under these conditions.

参考文章(65)
Jason V. Brooks, Synthia K. Furney, Ian M. Orme, Metronidazole Therapy in Mice Infected with Tuberculosis Antimicrobial Agents and Chemotherapy. ,vol. 43, pp. 1285- 1288 ,(1999) , 10.1128/AAC.43.5.1285
R. O. Loebel, E. Shorr, H. B. Richardson, The Influence of Foodstuffs upon the Respiratory Metabolism and Growth of Human Tubercle Bacilli. Journal of Bacteriology. ,vol. 26, pp. 139- 166 ,(1933) , 10.1128/JB.26.2.139-166.1933
Patricia L. Tavormina, William S. Reznikoff, Carol A. Gross, Identifying interacting regions in the beta subunit of Escherichia coli RNA polymerase Journal of Molecular Biology. ,vol. 258, pp. 213- 223 ,(1996) , 10.1006/JMBI.1996.0244
C A Reeve, A T Bockman, A Matin, Role of protein degradation in the survival of carbon-starved Escherichia coli and Salmonella typhimurium. Journal of Bacteriology. ,vol. 157, pp. 758- 763 ,(1984) , 10.1128/JB.157.3.758-763.1984
R. O. Loebel, E. Shorr, H. B. Richardson, The Influence of Adverse Conditions upon the Respiratory Metabolism and Growth of Human Tubercle Bacilli Journal of Bacteriology. ,vol. 26, pp. 167- 200 ,(1933) , 10.1128/JB.26.2.167-200.1933
Jeffery S. Cox, Bing Chen, Michael McNeil, William R. Jacobs, Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature. ,vol. 402, pp. 79- 83 ,(1999) , 10.1038/47042
James A. Triccas, Brigitte Gicquel, François-Xavier Berthet, Vladimir Pelicic, Use of fluorescence induction and sucrose counterselection to identify Mycobacterium tuberculosis genes expressed within host cells. Microbiology. ,vol. 145, pp. 2923- 2930 ,(1999) , 10.1099/00221287-145-10-2923
Theresa M. Michele, Chiew Ko, William R. Bishai, Exposure to antibiotics induces expression of the Mycobacterium tuberculosis sigF gene: implications for chemotherapy against mycobacterial persistors. Antimicrobial Agents and Chemotherapy. ,vol. 43, pp. 218- 225 ,(1999) , 10.1128/AAC.43.2.218
Yossef Av-Gay, Sarwat Jamil, Steven J. Drews, Expression and Characterization of the Mycobacterium tuberculosis Serine/Threonine Protein Kinase PknB Infection and Immunity. ,vol. 67, pp. 5676- 5682 ,(1999) , 10.1128/IAI.67.11.5676-5682.1999