**Author details**

the bacterium to the neighbouring cells before establishment of the adaptive immune response (Urdahl KB et al., 2011). Type I interferons regulate the levels of interferon-γ and production of the IL-1β which are critical determinants of immunity to tuberculosis (Novikov A et al., 2011). Eicosanoids play decisive roles in the fate of the infected macrophages (apoptosis versus necrosis) by regulating the level of tumor necrosis factor. Thus, several of the host molecular pathways converge to dictate the delicate balance between host immune response and mycobacterial pathogenesis. We need to further understand their inter-relation and cross regulation in greater details to tackle the mycobacterial infection appropriately. There are intensive research and development activities in progress around the globe to tackle the epidemic of tuberculosis. Bedaquiline-the new drug approved for treatment of the MDR tuberculosis-was released finally in December 2012. According to WHO report on tuberculosis 2013, there are around ten drugs in various phases of clinical trials and many in the preclinical stages (Table 1). Also there are many new TB vaccines in the various phases of clinical development. Whether they are pre-or post-exposure vaccines and other details viz. their immune-therapeutic potential, killed whole cell or extract etc. are nicely elaborated in the

Lead compounds Cyclopeptides, Diarylquinoline, DprE Inhibitors, InhA inhibitor, LeuRS

Translocase-1 inhibitors

Phase II AZD5847, Bedaquiline (TMC-207), Linezolid, *PA-824, Rifapentine,*

Phase III Delamanid (OPC-67689), Gatifloxacin, Moxiflloxacin, Rifapentine

Note: Four of the drugs in phase II trials (italicized) are novel and part of the combination regimens.

/CD45<sup>−</sup>

*SQ-109, Sutezolid (PNU-100480)*

The current research is also helping us to better understand the life cycle and survival strategies of the pathogen. Recently, work by Das B et al., 2013, suggested that M tb persists inside the

showed that the pathogen remains alive even after the full regimen treatment of the patients

produce low levels of reactive oxygen species, are quiescent in nature and have self renewal capability. This makes them an ideal place for M tb to survive for a long time. The immuneprivileged nature of the bone marrow also supports the dormant life of the pathogen and M tb is able to live a non replicating life inside the bone marrow mesenchymal stem cells (Das B. et al., 2013). The part of the extracellular life of M tb in the form of pellicle or biofilms inside the liquefied granuloma and alternate hiding places has yet to be clearly elucidated. The

mesenchymal stem cells in the bone marrow of tuberculosis patients. They

mesenchymal stem cells express drug efflux pumps,

Preclinical development CPZEN-45, DC-159a, Q203, SQ609, SQ641, TBI-166

inhibitor, Macrolides, Mycobacterial Gyrase inhibitors, Pyrazinamide analogs, Riminophenazines, Ruthenium (II) complexes, Spectinamides,

WHO report on tuberculosis, 2013.

80 Trends in Infectious Diseases

Laboratory toxicity testing PBTZ-169, TBA-354

**Table 1.** Development Pipeline for new TB drugs (WHO, 2013)

CD271+

/CD45<sup>−</sup>

with anti-TB drugs. The CD271+

Ramesh Chandra Rai

Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aru‐ na Asaf Ali Marg, New Delhi, India
