**8. Acknowledgement**

Work reported from the Sharma lab has been generously funded by the Department of Biotechnology-DBT- (Government of India), New Delhi

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**7** 

*Russia* 

*Mycobacterium tuberculosis* **Transcriptome** 

The infectious diseases caused by intracellular bacterial pathogens, such as *M. tuberculosis*, are among the most important problems in public health worldwide. The development of an infectious process depends on intricate interactions between the host defence systems and the specific systems regulating mycobacterial gene expression. Changes in expression in response to host defence are a necessary condition for the *M. tuberculosis* survival and functioning. Tracking these changes makes possible to analyze the biochemical cascades that are triggered in response to host defence mechanisms and to find the targets for designing new therapeutics and monitoring bacterial infections; in addition, these results are useful for both theoretical (for example, dynamics of the pathogen transcriptome changes during longterm persistence in the host) and applied (for example, the study of the bacterial response to

The completion of the *M. tuberculosis* genome sequence in 1998 (Cole et al., 1998) marked the beginning of the so called post genome era, the main characteristic of which are large scale studies of genome functional activity. The information on the bacterial genome organization allowed to construct macro- and microarrays containing fragments of a majority of ORFs, which enabled analysis of the pathogen transcription profile variations under different conditions. It's no wonder that the first study of the *M. tuberculosis* transcriptome using microarray technology was carried out in the first year after the publication of the genome sequence (Wilson et al., 1999). In as little as 5 years, there have been published many reports with the results of using microarrays for *in vitro* mycobacterial transcriptome analysis (for

However, the *in vivo* analysis of mycobacterial gene expression during infection process, which is of special scientific interest, is rather complicated, and this can explain a relatively small number of such works. Experiments with analysis of a pathogen transcriptome *in vivo* are determined by the choice of: (1) an experimental model of infection; (2) a method of pathogen RNA isolation; (3) a method of analysis of RNA or cDNA enriched in bacterial

**1. Introduction** 

various therapeutic interventions) research.

review, see (Butcher, 2004; Kendall et al., 2004)).

transcripts. The brief features of these steps are given in the review.

*In Vivo* **Studies – A Key to** 

**Understand the Pathogen** 

Tatyana Azhikina and Timofey Skvortsov

*Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS* 

**Adaptation Mechanism** 

Zhang, Y., Lathigra, R., Garbe, T., Catty, D. & Young, D. (1991). Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of *Mycobacterium tuberculosis.* Molecular Microbiology 5, 381-391.
