**6. References**


Lipid Surrounding of Mycobacteria: Lethal and Resuscitating Effects 255

Nazarova, Е.V., Zhogina, Y.А., Morozova, N.S., Shleeva, M.О., Sorokoumova, G.М.,

Nazarova, E.V., Shleeva, M.O., Morozova, N.S., Kudykina, Yu.K., Vostroknutova, G.N.,

Peyron, P., Vaubourgeix, J., Poquet, Y., Levillain, F., Botanch, C., Bardou, F., Daffé, M.,

Raynaud, C., Guilhot, C., Rauzier, J., Bordat, Y., Pelicic, V., Manganelli, R., Smith, I., Gicquel,

Russell, D.G., VanderVen, B.C., Lee, W., Abramovitch, R.B., Kim, M.J., Homolka, S.,

Schaloske, R.H., Blaesius, D., Schlatterer, C., & Lusche, D.F. (2007). Arachidonic acid is a

Schnappinger, D., Ehrt, S., Voskuil, M.I., Liu, Y., Mangan, J.A., Monahan, I.M., Dolganov, G.,

Shakina, Y.V., Troshkina, O.A., Petrova, E.E., Salina, E.G., Sorokoumova, G.M., Shvets, V.I.,

Shleeva, M., Mukamolova, G.V., Young, M., Williams, H.D., & Kaprelyants, A.S. (2004).

Smirnova, T.G., Mikulovich, J.L., Andreevskaya, S.N., Sorokoumova, G.M., Chernousova,

resuscitation. *Microbiology*, Vol. 150, Pt. 6, (June 2004), pp. 1687–1697 Shleeva, M.O., Kudykina, Y.K., Vostroknutova, G.N., Suzina, N.E., Mulyukin, A.L., &

antituberculosis drugs. *Zh. Mikrobiol. (Moscow)*, No. 6, pp. 7-11

*Cities"*, Moscow Russia, March 15-17, 2010, pp. 454-455

6, (June 2011), pp. 636-644

10, No. 9, (September 2009), pp. 943 - 948

(December 2007), pp. 1281–1289

No. 2, (March 2011), pp. 146-154

704

*Cell Host Microbe*, Vol. 8, No. 1, (July 2010), pp. 68-76

2008), pp. e1000204

Selischeva, А.А., Kaprelyants, А.S., & Shvets, V.I. (2010) The Influence of carbon source on antituberculous drug resistance of mycobacteria, *Proceedings of The Moscow International Scientific and Practical Conference "Biotechnology: Ecology of Big* 

Ruzhitsky, A.O., Selishcheva, A.A., Sorokoumova, G.M., Shvets, V.I., & Kaprelyants A.S. (2011). Role of lipid components in formation and reactivation of *Mycobacterium smegmatis* "nonculturable" cells. *Biochemistry (Moscow)*, Vol. 76, No.

Emile, J.F., Marchou, B., Cardona, P.J., de Chastellier, C., & Altare, F. (2008). Foamy macrophages from tuberculous patients' granulomas constitute a nutrient-rich reservoir for *M. tuberculosis* persistence. *PLoS Pathog*., Vol. 4, No. 11, (November

B., & Jackson M. (2002). Phospholipases C are involved in the virulence of *Mycobacterium tuberculosis. Mol. Microbiol.*, Vol. 45, No. 1, (July 2002), pp. 203-217 Russell, D.G., Cardona, P.-J., Kim, M.-J., Allain, S., & Altare F. (2009). Foamy macrophages

and the progression of the human tuberculosis granuloma. *Nature Immunology*, Vol.

Niemann, S., & Rohde, K.H. (2010). *Mycobacterium tuberculosis* wears what it eats.

chemoattractant for *Dictyostelium discoideum* cells. *J. Biosci*., Vol. 32, No. 7,

Efron, B., Butcher, P.D., Nathan, C., & Schoolnik, G.K. (2003). Transcriptional adaptation of *Mycobacterium tuberculosis* within macrophages: insights into the phagosomal environment. *J. Exp. Med.*, Vol. 198, No. 5, (September 2003), pp. 693-

Kaprelyants, A.S., & Selishcheva, A.A. (2007). Susceptibility of *Mycobacterium smegmatis*, grown on the media, contained various carbon substrates, to

Formation of 'non-culturable' cells of *Mycobacterium smegmatis* in stationary phase in response to growth under suboptimal conditions and their Rpf-mediated

Kaprelyants, A.S. (2011). Dormant ovoid cells of *Mycobacterium tuberculosis* are formed in response to gradual external acidification. *Tuberculosis (Edinb)*, Vol. 91,

L.N., Selishcheva, A.A., & Shvets V.I. (2011). Cardiolipin lysoderivatives suppress


Dole, V.P. (1956). A relation between non-esterified fatty acids in plasma and the metabolism of glucose. *J. Clin. Invest*., Vol. 35, No. 2, (February 1956), pp. 150-154 Fenhalls, G., Stevens, L., Moses, L., Bezuidenhout, J., Betts, J.C., Helden Pv.P., Lukey, P.T., &

Kanetsuna, F. (1985). Bactericidal effect of fatty acids on mycobacteria, with particular

Kaplan, G., Steyn, L.M., Bekker, L.G., Post, F.A., & Wainwright, H.C. (2003). *Mycobacterium* 

Kondo, E., & Kanai, K. (1976). An attempt to cultivate mycobacteria in simple synthetic

Kondo, E., & Kanai, K. (1985). Mechanism of bactericidal activity of lysolecithin and its

Lu, Y., Wu, Y.R., & Han, B. (2005). Anaerobic induction of isocitrate lyase and malate

McKinney, J.D., Honer zu Bentrup, K., Munoz-Elias, E.J., Miczak, A., Chen, B., Chan, W.T.,

Mishra, K.C., de Chastellier, C., Narayana, Y., Bifani, P., Brown, A.K., Besra, G.S., Katoch,

Mizushima, T., Natori, S., & Sekimizu, K. (1992). Inhibition of *Escherichia coli* DNA

Morris, R. P., Nguyen, L., Gatfield, J., Visconti, K., Nguyen, K., Schnappinger, D., Ehrt, S.,

Munoz-Elias, E.J., & McKinney, J.D. (2005). *Mycobacterium tuberculosis* isocitrate lyases 1 and

*Infect Immun*, Vol. 76, No. 1, (January 2008), pp. 127-140

102, No. 34, (August 2005), pp. 12200-12205

*Infect Immun*., Vol. 70, No. 11, (November 2002), pp.6330-6338

*Infect. Immun*., Vol. 71, No. 12, (December 2003), pp. 7099–7108

Vol. 29, No. 2, pp.127-141

pp.406-414

454

pp. 503-506

(June 2005), pp. 638-644

29, No. 3, (June 1976), pp.109-121

Duncan, K. (2002). In situ detection of *Mycobacterium tuberculosis* transcripts in human lung granulomas reveals differential gene expression in necrotic lesions.

reference to the suggested mechanism of intracellular killing. *Microbiol Immunol*.,

*tuberculosis* growth at the cavity surface: a microenvironment with failed immunity.

liquid medium containing lecithin-cholesterol liposomes. *Jpn. J. Med. Sci. Biol*, Vol.

biological implication. *Jpn. J. Med. Sci. Biol*, Vol. 38, No. 4, (August 1985), pp.181-194

synthase in submerged rice seedlings indicates the important metabolic role of the glyoxylate cycle. *Acta Biochim. Biophys. Sin. (Shanghai)*, Vol. 37, No. 6, (June 2005),

Swenson, D., Sacchettini, J.C., Jacobs, Jr. W.R., & Russell, D.G. (2000). Persistence of *Mycobacterium tuberculosis* in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. *Nature*, Vol. 406, No. 6797, (August 2000), pp. 735–738 Mikulovich, J.L., Andreevskaya, S.N., Smirnova, T.G., Sorokoumova, G.M., Chernousova,

L.N., Selishcheva, A.A., & Shvets, V.I. (2010). The influence of cardiolipin liposomes on growth and survival of *Mycobacterium tuberculosis* H37Rv in vitro, *Proceedings of The Moscow International Scientific and Practical Conference "Biotechnology: Ecology of Big Cities"*, Moscow, Russia, March 15-17, 2010, pp. 453-

V.M., Joshi, B., Balji, K.N., & Kremer, L. (2008). Functional role of the PE domain immunogenicity of the *Mycobacterium tuberculosis* triacylglycerol hygrolase LipY.

topoisomerase I activity by phospholipids. *Biochem. J.,* Vol. 285, Part. 2, (July 1992),

Liu, Y., Heifets, L., Pieters, J., Schoolnik, G., & Thompson, C.J. (2005). Ancestral antibiotic resistance in *Mycobacterium tuberculosis*. *Proc. Natl. Acad. Sci. U.S.A.*, Vol.

2 are jointly required for *in vivo* growth and virulence. *Nature Med.*, Vol. 11, No. 6,


**14** 

**Heat Shock Proteins in** *Mycobacterium* 

Tuberculosis (TB) is an infectious disease of global concern. Worldwide TB kills two million people each year. About 90% of those infected with *Mycobacterium tuberculosis* have asymptomatic, latent TB infection (sometimes called LTBI) (Smith, 2003; Wayne & Sohaskey, 2001). Years after initial infection, the bacilli may resume growth, the outcome of which is active TB. If left untreated, the death rate for active TB cases is more than 50%. Approximately 95% of new cases and 98% of deaths occur in developing nations, where human immunodeficiency virus (HIV) infections are common, this is generally because of the unavailability of proper treatment. The causative agent, *M. tuberculosis* has a cell wall which has a very low permeability for most antibiotics and chemotherapeutic agents. Another critical problem is the development of multi-drug resistant TB (MDR-TB) or extremely drug resistant TB (XDR-TB) (Chiang et al., 2010; Eismont, 2009; WHO report, 2010). Every year in the world, around 440,000 new MDR-tuberculosis cases are found due to bacilli that are resistant to the two main antitubercular drugs, isoniazid and rifampicin. The XDR-TB is a recently developed form. The mortality rate in the case of XDR-TB can go from 50 to 100%. *M. tuberculosis* mutants, resistant to any single drug are naturally present in any large bacterial population, irrespective of exposure to drugs. Despite the availability of effective chemotherapy and the moderately protective vaccine, new anti-TB agents are urgently needed to decrease the global incidence of TB (Cox et al., 2006; Ducati et al., 2006).

**2. Mycobacterial infection and survival of pathogen inside the host** 

On infection, *M. tuberculosis* resides mainly in the host macrophage, inside an endocytic vacuole called the phagosome. The pathogenic mycobacteria inhibit phagosome-lysosome fusion (Hestvik et al., 2005; Pieters & Gatfield, 2002). Lack of maturation of phagosomes containing pathogenic *M. tuberculosis* within macrophages has been widely recognized as a crucial factor for the persistence of mycobacterial pathogen. Mycobacteria have been shown to remain within phagosomes for a long time after infection by EM analysis (Jordao et al., 2008). It is unclear whether blocking of phagosome–lysosome fusion is essential for *M.* 

**1. Introduction** 

*tuberculosis***: Involvement in Survival** 

**and Virulence of the Pathogen** 

Divya Bajaj and Janendra K. Batra

*National Institute of Immunology* 

*Aruna Asaf Ali Marg* 

*New Delhi India* 

the survival both susceptible and resistant strains of *Mycobacterium tuberculosis*. *Russian Journal of Biopharmaceuticals*, Vol. 3, No. 2, pp. 19-27

