**5. Acknowledgment**

252 Understanding Tuberculosis – Deciphering the Secret Life of the Bacilli

All of the presented results support an idea that amount of FA in surrounding medium play a determinative role in formation and reactivation of *M. smegmatis* nonculturable cells (fig. 12). Thus 0.18-10.6 μМ of oleic acid possess a resuscitation effect. A little larger number of FA (33-59 μМ ) accumulates in culture liquid during transition into nonculturable state. And finally, as it was shown previously, oleic acid in amount of 92 μМ inhibits growth of

Fig. 12. Correlation between a state of *M. smegmatis* and a quantity of extracellular FA.

and resistant to anti-tuberculosis drugs in such conditions [Nazarova, 2010].

Pathogen *M. tuberculosis* by itself as well as particular bacterial lipids are reported to induce loading of macrophages with lipid bodies resulting in formation of foamy macrophages [Russell, 2009]. So it seems that mycobacterial lipids passed by macrophages to each other cause such differentiation of immune cells influencing on total tissue remodelling of the infection site. Inside of such altered foamy macrophages mycobacteria have an access and actually use host lipids from the lipid drops, which leads to their transition into a state similar to the nonreplicating state [Peyron, 2008]. Cultivation of mycobacteria in medium enriched with lipid substances showed that bacilli do form cells with changed morphology

When as a consequence of total 'lipidation' of granuloma macrophages mycobacteria find themselves in the excess of surrounding lipids, this excess induces a dormant state in pathogens. If immune system of the host is active enough, granuloma either undergoes resolution, or remains balanced. But in case of active disease development caseum is accumulated in the centre of some granulomas; this leads to necrosis and collapse of granuloma, and to release of virulent bacilli into airways [Kaplan, 2003]. Since during this release mycobacteria appear to be finally not in stressful conditions and not surrounded or surrounded with a little amount of lipid substances, they might reactivate, as it can be

mycobacterial cells.

**4. Conclusion** 

The authors acknowledge Dr. Arseny S. Kaprelyants and his laboratory at Bach Institute of Biochemistry (Russian Academy of Sciences), and Dr. Larisa N. Chernousova's research group at Central TB research Institute (Russian Academy of Medical Sciences) for consistent and efficient collaboration.
