Analusis Of Potential Drug Target Of Drug Resistant Mycobacterium Tuberculosis Based On Bioinformatics

Tuberculosis(TB) is one of the most serious global health issues, the pathogenesis of which is still not clear. In recent years, owing to the abuse of antibiotics and the epidemic of co-infection of Mycobacterium Tuberculosis and HIV, the worsening problem of mycobacterium tuberculosis multiple drug-resistance has became a major challenge for TB control, which is also an important reasons for the global spread and worsened epidemic of TB. Anti-tuberculosis drugs, such as rifampin and isoniazid, were discovered firstly in 1963, since then, no novel efficient anti-tuberculosis drug that could substitute for the traditional ones was developed. The reason is that the quantity of effective therapeutic targets for TB control is far from enough, which cannot meet the current needs, especially for the multiple drug-resistant TB treatment. Thus, the high-throughput screening for therapeutic targets is the first and the most important step for the development of novel anti-tuberculosis drugs and for the TB controlThe cell wall of mycobacterium tuberculosis is mainly composed of capsule, mycolic acid, peptidoglycan, arabinose and intima. These components play an important role in the process that maintain the integrity of the mycobacterium tuberculosis cell morphology, against the erosion of chemicals, escape the immune, generate the drug resistance and increase the pathogenicity of mycobacterium tuberculosis. So, the mycobacterium tuberculosis cell wall related components and biosynthesis pathways could be used as the target of anti-tuberculosis drugs. Just as the traditional anti-tuberculosis drugs including isoniazid, the therapeutic target of which is the inhibition of the mycolic acid synthesis pathway [6]. But, the mycobacterium tuberculosis genotype is extremely complex and changeable, traditional targets such as inh A, ahp C, nadh, kat G, Kas A have all showed mutations associated with drug resistance. Hence, it is urgent to screen new mycobacterium tuberculosis cell wall relevant genes. In addition, the components and functions of mycobacterium tuberculosis cell wall are quite complex and various. Traditional methods to screen the mycobacterium tuberculosis cell wall associated genes are expensive and inefficient, which use the technologies of gene knockout and RNA interference to screen the potential cell wall synthesis associated genes or the target molecules in metabolism. Along with the limitation of experimental methodology, there is still no efficient technology to systematically screen the cell wall synthesis relevant molecules. Thus, the foundation of a novel module for panoramic scanning and screening of the mycobacterium tuberculosis cell wall synthesis related genes is awaited urgently. For the reasons above, in our study, we collected all gene microarrays of mycobacterium tuberculosis H37 Rv before the date May 2013, which totally contained 2738 microarrays of 43 series. Then we established the co-regulatory networks of mycobacterium tuberculosis cell wall synthesis associated genes, unknown genes and other genes by means of integration and clustering [10]. And the module analysis and the high-throughput annotation of mycobacterium tuberculosis cell wall associated genes provided a molecular basis for the research and development of novel efficient, sensitive anti-tuberculosis drugs with less harmful effects.Until now just understood that INH effect TB on the both sides of this, Kat G gene and cell wall.It had proved that Kat G can activate INH inducible gene Rv0341, Rv0341 and Rv0341. Tuberculosis can change the thickness of cell wall to resistant INH. About INH had an unsolved mysteries that how to eliminate the TB. INH must have some more profound influence on TB and destroy the bacterium. But how to observed and uncovered this influence is difficulty. It is often the most important. How to research the drug-target. We want to use side-effect similarity to find new drug-target.It is a complex phenomenological that medicine cure disease, People used primary function to beat disease and circumvention side-effect, But these side-effect were used to predicted the drug-target [15864270]. Monica Campillos used phenotypic side-effect similarities to infer two drugs share a target [18621671]. The theory sustained our reason that similar side-effect was used to search drug-target. INH is the most major drug for treat TB. However the drug could injure our body for example liver, vitamin B6 and Oxidative stress and so on. It is hint that had similar target in the organ or biological process. INH also influence therefor both bacterium and human had co-target of INH. The sequence of gene of human compared with sequence gene of TB. Large scale sequence data were compared to find a part of the same in the gene of human and bacterium. And verify possibility by method of statistics and biology. It is very slowly that targets for drugs have so far been predicted on the basis of molecular or cellular features. We increased the efficiency that find new drug-target. Take the reason that isoniazid how to kill the TB.