Mycobacterium Tuberculosis Essay

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Mycobacterium tuberculosis is responsible for two million deaths per year and infects one third of the global population throughout their lifetime (Sharma, 2006). The highest prevalence of tuberculosis infection throughout the world is in sub-Saharan Africa and Southeast Asia (Raviglione et al, 1995).

Difficulties in Treatment

Emergence of multi Drug Resistant Tuberculosis

Up until approximately 1984, the prevalence of tuberculosis was rapidly decreasing by an average of 6% per year. However, beginning in 1985, this decline reversed itself and the prevalence of Tuberculosis started to rapidly increase. One of the reasons for this increase in prevalence is the emergence of a multi-drug resistant form of tuberculosis.(Dooley 1992). These strains have been termed multi-drug resistant due to their resistance to both major anti-tuberculosis drugs known as rifampicin and isoniazid(Zager, 2008). Resistance to these drugs result primarily from incorrect drug prescription from health providers, lack of access to drug supply, improper adherence by patients, and poor quality control for drugs (Shah et al, 2007).

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However, another important factor to consider is the emergence of human immunodeficiency virus. As described in the graph above, as HIV emerged and began to continuously become more prevalent, so did the prevalence of Tuberculosis. It is possible that not only can HIV increase the risk of reactivating a latent form of Mycobacterium tuberculosis, but it also increase the speed of Tuberculosis progression (Corbett et al, 2003). In addition, it is hypothesized that HIV infection could possibly lead to malabsorption of anti-tuberuclosis drugs and led to the acquisit...

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...ible for the role that Valine 215 and Isoleucine 214 accomplish in establishing the hydrophobicity of KasB. Additionally, the importance of Valine 215 and Isoleucine 214 was further solidified when the replacement of these residues with Alanine 211 led to the loss of hydrophobicity of the entire core (Sudharsan et al, 2007).

Tunnel
As previously mentioned, Thiolactomycin was found to bind poorly to KasB enzyme. In part, this is due to unique positioning of Arg 200 (highlighted in pink) which binds β6 and α10. This causes an apparent elongation of α10 (highlighted in green) which then causes an axial shift towards the surface of the protein. Subsequently, results in Arg 213 (highlighted in cyan) further shifted toward surface. Furthermore, this causes the opening of the tunnel become more restricted which may have prevent the entrance of drugs such as Thiolactomycin.
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