Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1081510.32607/20758251-2009-1-2-73-77ArticlesСтатьиResearch ArticleM. tuberculosis gene Expression during Transition to the “Non-Culturable” StateM. tuberculosis gene Expression during Transition to the “Non-Culturable” StateSalinaE Gelenasalina@mail.ruMollenkopfH Jmollenkopf@mpiib-berlin.mpg.deKaufmannS HEKaprelyantsA SA.N. Bach Institute of Biochemistry, RASMax Planck Institute for Infection Biology1509200912NO2 (2009)№2 (2009)737717012020Copyright ©; 2009, Salina E.G., Mollenkopf H.J., Kaufmann S.H., Kaprelyants A.S.Copyright ©; 2009, Salina E.G., Mollenkopf H.J., Kaufmann S.H., Kaprelyants A.S.2009Salina E.G., Mollenkopf H.J., Kaufmann S.H., Kaprelyants A.S.Salina E.G., Mollenkopf H.J., Kaufmann S.H., Kaprelyants A.S.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10815

We analyzed the gene expression profile under specific conditions during reversible transition of M. tuberculosis cells to the “non-culturable” (NC ) state in a prolonged stationary phase. More than 500 genes were differentially regulated, while 238 genes were upregulated over all time points during NC cell formation. Approximately a quarter of these upregulated genes belong to insertion and phage sequences indicating a possible high intensity of genome modification processes taking place under transition to the NC state. Besides the high proportion of hypothetical/conserved hypothetical genes in the cohort of upregulated genes, there was a significant number of genes belonging to intermediary metabolism, respiration, information pathways, cell wall and cell processes, and genes encoding regulatory proteins. We conclude that NC cell formation is an active process involved in the regulation of many genes of different pathways. A more detailed analysis of the experimental data will help to understand the precise molecular mechanisms of dormancy/latency/persistence of M. tuberculosis in the future. The list of upregulated genes obtained in this study includes many genes found to be upregulated in other models of M. tuberculosis persistence. Thirteen upregulated genes, which are common for different models, can be considered as potential targets for the development of new anti-tuberculosis drugs directed mainly against latent tuberculosis.

M. tuberculosislatent tuberculosis“non-culturable” cellsglobal gene expression profileGangadharam P. R. J. Tuber. Lung Dis., 1995, 76, 477-479.Wayne L. G. and Lin K.-Y. Infect. Immun., 1982, 37, 1042-1049.Wayne L. G. and Hayes L. G. Infect. Immun., 1996, 64, 2062-2069.Mukamolova G. V., Salina E. G., Kaprelyants A. C. in National Institute of Allergy and Infectious Diseases, NIH (Georgiev, V., ed), Humana Press, USA, 2008, 1, 83-90.Voskuil M. I., Visconti K. C., Schoolnik G. K. Tuberculosis (Edinb.), 2004, 84, 218-227.Shao L., Zhang W., Zhang S., Chen CY., Jiang W., Xu Y., Meng C., Weng X., Chen Z.W. AIDS, 2008, 22(17), 2241-508.Muttucumaru D. G., Roberts G., Hinds J., Stabler R. A., Parish, T. Tuberculosis (Edinb.), 2004, 84, 239-246.Bacon J., James B. W., Wernisch L., Williams A., Morley K. A., Hatch G.J., Mangan J.A., Hinds J., Stoker N.G., Butcher P.D., and Marsh P.D. Tuberculosis (Edinb.), 2004, 84, 205-217.Hampshire T., Soneji S., Bacon J., James B. W., Hinds J., Laing K., Stabler R. A., Marsh P. D., and Butcher P. D. Tuberculosis (Edinb),2004, 84, 228-238.Schnappinger D., Ehrt S., Voskuil M. I., Liu Y., Mangan J. A., Monahan I. M., Dolganov G., Efron B., Butcher P. D., Nathan C., Schoolnik G. K. J. Exp Med., 2003, 198(5), 693-704.Karakousis P. C., Yoshimatsu T., Lamichhane G., Woolwine S. C., Nuermberger E.L., Grosset J., Bishai, W. R. J. Exp. Med., 2004, 200, 647-657.Betts J. C., Lukey P. T., Robb L. C., McAdam R. A., and Duncan K. Mol. Microbiol., 2002, 43, 717-731.Rustad T. R., Harrell M. I., Liao R, Sherman D. R.. PLoS ONE, 2008, 3(1), 1502.Boshoff H. I., Myers T. G., Copp B. R., McNeil M. R., Wilson M. A., and Barry C. E., 3rd J. Biol. Chem., 2004, 279, 40174-40184.