Dear Nagendra, 

I have summarized a number of publications which can give you a good idea on how to target the microorganism with negligible side effects to humans.

1-Therapeutic applications

Because TB requires cholesterol to persist during an infection, inhibiting the Mce4 transporter can be a novel therapeutic option. Understanding the mechanism of the Mce4 transport system can provide insight into possible anti-mycobacterial targets.

Targeting the KstR regulation system may also be a possible treatment. If the KstR proteins are prohibited from unbinding its operator and de-repressing its regulon, TB’s cholesterol catabolism genes would not be expressed. As a result, the ability for TB to persist inside macrophages would be lost and thus would be faster to treat.

Within the cholesterol catabolism pathway, there are many metabolites that may be toxic. Cholestenone, the first product of the cholesterol pathway, has shown to be toxic and can kill the cell. Cholestenone is used up by CYP125, and knocking out CYP125 causes an accumulation of toxic cholestenone which kills the cell.Furthermore, a previous study revealed that knocking out HsaC resulted in catechol formation15, which can harm the cell due to formation of free radicals that can cause irreparable DNA damage. Inhibiting CYP125 and HsaC may also be possible therapeutic options in which the cell poisons itself to death .

Ouellet, H. et al. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol. Microbiol. 77, 730 (2010).

Ouellet, H., Johnston, J. B. & de Montellano, P. R. O. Cholesterol catabolism as a therapeutic target in Mycobacterium tuberculosis. Trends Microbiol. 19, 530 (2011).

Schweigert, N., Zehnder, A. J. & Eggen, R. I. Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. Environ. Microbiol. 3, 81 (2001).

https://microbewiki.kenyon.edu/index.php/Mycobacterium_tuberculosis

2-A recent review entitled " Virulence factors of the Mycobacterium tuberculosis complex"  by Forrellad MA. et al. published in Virulence. 2013 Jan 1; 4(1): 3–66 lists the virulence factors that are mainly involved in the interaction of MTBC species with the host macrophages : One set of these virulence factors is implicated in the adaptation of the bacilli to the limited nutritional condition of the macrophages and includes proteins required for the uptake of nutrients and ions as well as for the switching of carbon metabolism that occurs when mycobacteria reside inside host cells. Another set comprises proteins that participate in the mechanisms triggered by mycobacteria to counteract the microbicidal host cell responses, such as: (1) arresting the normal progression of the phagosome and increasing the resistance to host toxic compounds (cell wall barrier and specific effectors), (2) escaping from the intracellular compartment and (3) avoiding the development of localized, productive immune responses.

The above mentioned factors if targeted, the target will be solely for the microbe and it is expected that side effects of drugs targeting these factors will be minimal. 

The following is the review abstract for quick view:

Abstract

The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544749/

3-Another review which may be interesting to read entitled " THE MAGIC BULLETS AND TUBERCULOSIS DRUG TARGETS" by Zhang Y. published in Annual Review of Pharmacology and Toxicology Vol. 45: 529-564 (Volume publication date February 2005).

ABSTRACT 

Modern chemotherapy has played a major role in our control of tuberculosis. Yet tuberculosis still remains a leading infectious disease worldwide, largely owing to persistence of tubercle bacillus and inadequacy of the current chemotherapy. The increasing emergence of drug-resistant tuberculosis along with the HIV pandemic threatens disease control and highlights both the need to understand how our current drugs work and the need to develop new and more effective drugs. This review provides a brief historical account of tuberculosis drugs, examines the problem of current chemotherapy, discusses the targets of current tuberculosis drugs, focuses on some promising new drug candidates, and proposes a range of novel drug targets for intervention. Finally, this review addresses the problem of conventional drug screens based on inhibition of replicating bacilli and the challenge to develop drugs that target nonreplicating persistent bacilli. A new generation of drugs that target persistent bacilli is needed for more effective treatment of tuberculosis.

http://www.annualreviews.org/doi/full/10.1146/annurev.pharmtox.45.120403.100120

Hoping this will be helpful,

Rafik

We published this article about proteins exclusive of M. tuberculosis complex (Mtbc) and absent in non-Mtbc mycobacteria whose genome was sequenced in 2014. Just the first part of results, the rest is about antigen evaluation. It may help you. We did not compared with human genome.

go for the nonhomologous drug targets of MTb search on google u will find many papers.

You may get maximum information for ant-TB therapy and the target on which peptide is acting.

http://webs.iiitd.edu.in/raghava/antitbpdb/

Article AntiTbPdb: a knowledgebase of anti-tubercular peptides