Mycobacterium tuberculosis

Mycobacterium tuberculosis enoyl-ACP reductase InhA Tuberculosis is a serious, widespread and often fatal infectious disease caused by Mycobacterium tuberculosis. Tuberculosis has long been treated using the drug isoniazid and it has been found that the target for the drug is an NADH-specific enoyl-acyl carrier protein (ACP) reductase coded for by the inhA gene. The exact mechanism of action for isoniazid is still unknown and remains fertile ground for research.

The prevalence and mortality of tuberculosis in the world today, coupled with strains that are increasingly resistant to front-line antibiotic treatments, the isolation of the mechanism and suggestion of other targets for tuberculosis treatments is a high priority. A naturally occurring mutation at residue S94 has been identified, which engenders resistance to isoniazid. The exact nature of the changes this mutation causes in the active site is unknown, and identification of these changes could lead to fresh research into new drugs for treating tuberculosis, or help identify a cofactor to increase the effectiveness of isoniazid.

These two systems play a role in either human pain pathways or human pathogenic bacterial activity. Further understanding of the relationship between the structure and dynamics of these systems has the potential to provide targets for pharmaceutical research. This is especially important in the case of the bacterial protein; in an age where antibiotic resistance is becoming more serious and widespread, new front-line drugs are needed in order to prevent the deaths of millions of people. Novel targets for research have a role to play in the search for more effective antibiotics, and understanding the structure and dynamics of these proteins—and how they are related—is an important step towards this.