Sandbox Reserved 1068: Difference between revisions

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[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] is the causative agent of [http://www.cdc.gov/tb/ Tuberculosis] (TB), an infectious disease that affects one-third of the worlds population. Two TB-related conditions exist: latent TB infection and active TB disease. Currently, there are four regimens that are approved for the treatment of latent TB infection through the use of the antibiotics isoniazid, rifampin, and rifapentine.TB disease can also be treated through various antibiotic regimens. There are 10 drugs currently approved by the FDA for treating TB disease. The first-line anti-TB agents are the antibiotics isoniazid, rifampin, ethambutol, and pyrazinamide <ref>Tuberculosis (TB). Ed. Sam Posner. Centers for Disease Control and Prevention, n.d. Web. 9 Apr. 2015.</ref>. Although various treatments for TB infection and TB disease exist, the emergence of [http://www.cdc.gov/tb/publications/factsheets/drtb/mdrtb.htm multi-drug] and [http://www.cdc.gov/tb/topic/drtb/xdrtb.htm extensively-drug] resistant strains of ''M. tuberculosis'' has increased the need for anti-tubercular agents with novel modes of action.

[http://en.wikipedia.org/wiki/Iron#Biological_role Iron] is essential for mycobacterial growth and pathogenesis, therefore the pathways for iron acquisition are potential targets for antibacterial therapies.''M. tuberculosis'' obtains iron through two different pathways: chelating iron from the host through the siderophore mycobactin and the degradation of heme released from damaged red blood cells<ref name="1a"/>. MbtI catalyses the first committed step in the biosynthesis of the siderophore mycobactin and is a potential target for inhibition (Figure 1). The salicylate synthase activity of MbtI produces salicylate and pyruvate from chorismate through an isochorismate intermediate. Inhibition of MbtI activity would decrease the production of salicylate and therefore the synthesis of mycobactin; leading to a decrease in iron acquisition and pathogenesis of ''M. tuberculosis''<ref name= "7a"/> <ref name="1a"/><ref name="5a"/>.

[http://en.wikipedia.org/wiki/Iron#Biological_role Iron] is essential for mycobacterial growth and pathogenesis, therefore the pathways for iron acquisition are potential targets for antibacterial therapies.''M. tuberculosis'' obtains iron through two different pathways: chelating iron from the host through the siderophore mycobactin and the degradation of heme released from damaged red blood cells<ref name="1a"/>. MbtI catalyses the first committed step in the biosynthesis of the siderophore mycobactin and is a potential target for inhibition (Figure 10). The salicylate synthase activity of MbtI produces salicylate and pyruvate from chorismate through an isochorismate intermediate. Inhibition of MbtI activity would decrease the production of salicylate and therefore the synthesis of mycobactin; leading to a decrease in iron acquisition and pathogenesis of ''M. tuberculosis''<ref name= "7a"/> <ref name="1a"/><ref name="5a"/>.

[[Image:Screen Shot 2015-04-10 at 1.27.15 PM.png‎|500 px|center|thumb|Figure 3: Reaction catalyzed by MbtI in the mycobactin biosynthesis pathway<ref name= "2a"/>.]]

[[Image:Screen Shot 2015-04-10 at 1.27.15 PM.png‎|500 px|center|thumb|'''Figure 10:''' Reaction catalyzed by MbtI in the mycobactin biosynthesis pathway. MbtI catalyses the conversion of chorismate to salicylate and pyruvate. Salicylate (red) is then involved in the biosynthesis of mycobactin T <ref name= "2a"/>.]]

==Inhibition Studies==

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 [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] is the causative agent of [http://www.cdc.gov/tb/ Tuberculosis] (TB), an infectious disease that affects one-third of the worlds population. Two TB-related conditions exist: latent TB infection and active TB disease. Currently, there are four regimens that are approved for the treatment of latent TB infection through the use of the antibiotics isoniazid, rifampin, and rifapentine.TB disease can also be treated through various antibiotic regimens. There are 10 drugs currently approved by the FDA for treating TB disease. The first-line anti-TB agents are the antibiotics isoniazid, rifampin, ethambutol, and pyrazinamide <ref>Tuberculosis (TB). Ed. Sam Posner. Centers for Disease Control and Prevention, n.d. Web. 9 Apr. 2015.</ref>.  Although various treatments for TB infection and TB disease exist, the emergence of [http://www.cdc.gov/tb/publications/factsheets/drtb/mdrtb.htm multi-drug] and [http://www.cdc.gov/tb/topic/drtb/xdrtb.htm extensively-drug] resistant strains of ''M. tuberculosis'' has increased the need for anti-tubercular agents with novel modes of action.
-[http://en.wikipedia.org/wiki/Iron#Biological_role Iron] is essential for mycobacterial growth and pathogenesis, therefore the pathways for iron acquisition are potential targets for antibacterial therapies.''M. tuberculosis'' obtains iron through two different pathways: chelating iron from the host through the siderophore mycobactin and the degradation of heme released from damaged red blood cells<ref name="1a"/>. MbtI catalyses the first committed step in the biosynthesis of the siderophore mycobactin and is a potential target for inhibition (Figure 1). The salicylate synthase activity of MbtI produces salicylate and pyruvate from chorismate through an isochorismate intermediate. Inhibition of MbtI activity would decrease the production of salicylate and therefore the synthesis of mycobactin; leading to a decrease in iron acquisition and pathogenesis of ''M. tuberculosis''<ref name= "7a"/> <ref name="1a"/><ref name="5a"/>.
+[http://en.wikipedia.org/wiki/Iron#Biological_role Iron] is essential for mycobacterial growth and pathogenesis, therefore the pathways for iron acquisition are potential targets for antibacterial therapies.''M. tuberculosis'' obtains iron through two different pathways: chelating iron from the host through the siderophore mycobactin and the degradation of heme released from damaged red blood cells<ref name="1a"/>. MbtI catalyses the first committed step in the biosynthesis of the siderophore mycobactin and is a potential target for inhibition (Figure 10). The salicylate synthase activity of MbtI produces salicylate and pyruvate from chorismate through an isochorismate intermediate. Inhibition of MbtI activity would decrease the production of salicylate and therefore the synthesis of mycobactin; leading to a decrease in iron acquisition and pathogenesis of ''M. tuberculosis''<ref name= "7a"/> <ref name="1a"/><ref name="5a"/>.
-[[Image:Screen Shot 2015-04-10 at 1.27.15 PM.png‎|500 px|center|thumb|Figure 3: Reaction catalyzed by MbtI in the mycobactin biosynthesis pathway<ref name= "2a"/>.]]
+[[Image:Screen Shot 2015-04-10 at 1.27.15 PM.png‎|500 px|center|thumb|'''Figure 10:''' Reaction catalyzed by MbtI in the mycobactin biosynthesis pathway. MbtI catalyses the conversion of chorismate to salicylate and pyruvate. Salicylate (red) is then involved in the biosynthesis of mycobactin T <ref name= "2a"/>.]]
 ==Inhibition Studies==