**Author details**

Matthias Stehr1 , Ayssar A. Elamin1 and Mahavir Singh1,2\*

\*Address all correspondence to: Mahavir.Singh@helmholtz-hzi.de

1 LIONEX Diagnostics and Therapeutics GmbH, Braunschweig, Germany

2 Department of Genome Analytics, Helmholtz Centre for Infection Research, Braunsch‐ weig, Germany

### **References**

[1] Murphy D. J., Brown J. R. Identification of gene targets against dormant phase *Mycobacterium tuberculosis* infections. BMC Infect. Dis. 2007;7 84.


**7. Conclusion**

46 Tuberculosis - Current Issues in Diagnosis and Management

**Author details**

Matthias Stehr1

weig, Germany

**References**

The formation of lipid inclusions during infection in the host as well as in the pathogen during intracellular infection with *M. tuberculosis* and *M. leprae* plays an important role in pathogen‐ esis. A hallmark of intracellular infection is the formation of foamy macrophages. *M. tubercu‐ losis* and *M. leprae* induce the formation of lipid droplets in the host cell. The accumulated lipids are used as energy and carbon source. In fact *M. tuberculosis* seems to switch completely to fatty acid catabolism at the transition from the acute to the chronic phase of infection. The central role of fatty acid metabolism during the dormant state of *M. tuberculosis* is underlined by the finding that both isocitrate lyase, icl and icl2, are essential for intracellular replication in the lung [79,80]. The TAG metabolism and the resulting formation of lipid inclusions of host and pathogen play a fundamental role in infection. Indeed TAG-derived fatty acids from the host cell are imported into *M. tuberculosis* and incorporated into bacterial TAG [46]. In conclusion the enzymes involved in lipid droplet metabolism are essential for survival of the pathogen in the lung and thus attractive targets for novel drugs. Especially enzymes with DGAT activity such as Tgs and Ag85A seem to be promising drug target candidates. Another promising targets seem to be the recently discovered cell wall associated and secreted esterases, which are involved in the utilization of host cell lipids such as Rv0183 and LipY [55, 75,76]. Future studies should also focus on the lipid metabolism of *M. leprae*, an organism which upregulates several genes of the host´s lipid metabolism during infection [92]. The regulation of lipid droplet formation in the host cell is another important topic. Recent sudies revealed that intracellular pathogens induce the expression of LDL receptor and scavenger receptors CD36 and LOX1 for the internalization of native and oxidized fatty acids. Especially the generation of oxidized lipids by macrophage-derived reactive oxygen species seems to be an

important mechanism for the induction of scavenger receptors.

\*Address all correspondence to: Mahavir.Singh@helmholtz-hzi.de

1 LIONEX Diagnostics and Therapeutics GmbH, Braunschweig, Germany

*Mycobacterium tuberculosis* infections. BMC Infect. Dis. 2007;7 84.

and Mahavir Singh1,2\*

2 Department of Genome Analytics, Helmholtz Centre for Infection Research, Braunsch‐

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**Chapter 4**

**The Role of Antibodies in the Defense Against**

Throughout history tuberculosis (TB) has been a health problem for humanity. In the beginning of civilization, when human population densities were sparse, this disease may have been fairly harmless. However, with the increase in population densities, probably from the 17th to

Bacille Calmette Guérin (BCG) is effective to prevent miliary and meningeal TB in infants [1]. The reports about the efficacy of this vaccine for the prevention of adults pulmonary TB are contradictory and the consensus is that the protection conferred by BCG against this form of TB is questionable [1]. The wide use of BCG vaccination has been unable to prevent nearly two million deaths associated with TB that are produced every year. Currently the World Health Organization no longer recommends BCG vaccination in children born from HIVpositive mothers which complicate the implementation of BCG vaccination programs [2]. The imple‐ mentation of standard drug treatment for TB is difficult in the areas of the highest incidence of the disease. Treatment is further complicated by the limited effectiveness of the current

Nowadays there is an increasing realization of the need for new animal models to test vaccine efficacy in more realistic scenarios, overcoming the limitations of current models in use. In addition, the elucidation of the significance of antibody-mediated defense against intracellular pathogens, in particular against *Mycobacterium tuberculosis*, constitutes an exciting new

> © 2013 Acosta et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

approach to improve the rational design of new vaccines, therapies and diagnostics.

**Tuberculosis**

Armando Acosta, Yamile Lopez,

Aharona Glatman-Freedman

http://dx.doi.org/10.5772/53950

**1. Introduction**

Norazmi Mohd Nor, Rogelio Hernández Pando, Nadine Alvarez, Maria Elena Sarmiento and

Additional information is available at the end of the chapter

19th centuries, TB took epidemic proportions [1].

therapeutic schemes against drug resistant strains of TB [3-5].

