MRNA Interferases from Mycobacterium tuberculosis
From DrugPedia: A Wikipedia for Drug discovery
Revision as of 10:25, 6 September 2008
mRNA Interferases from Mycobacterium tuberculosis : a drug candidate for tuberculosis therapy Tuberculosis, an airborne infection that mainly affects the lungs, is classified as a “global health emergency” by the World Health Organisation. It is the most deadly and widespread major infectious disease, claiming the lives of two to three million people a year – one person every 15 seconds. The bacterium’s ability to lie dormant allows it to evade antibiotic treatment because most antibiotics target growing cells. Added to this, there has been a dramatic increase in multi-drug resistant strains of Mycobacterium tuberculosis and increased susceptibility to the disease of HIV-infected individuals. Effective treatment for TB currently requires combinations of expensive drugs for sustained periods of six to 12 months. Toxin targets are also of practical interest because they could be potential new drug targets in pathogenic bacteria Prokaryotic chromosomes code for toxin–antitoxin (TA) loci, often in multiple copies. Experimental evidence indicates that TA loci are stress-response elements that help cells survive unfavorable growth conditions. The first gene in a TA operon codes for an antitoxin that combines with and neutralizes a regulatory ‘toxin’, encoded by the second gene. Mycobacterium tuberculosis has 65 chromosomal toxin–antitoxin loci, including 3 relBE and 9 mazEF loci The toxin component of TA operon MazF proteins involved in RNA interferase. These proteins chop up RNA in a sequence specific manner, which potentially arrests the growth of Mycobacterium tuberculosis. It has been proved that mRNA interferases target longer RNA sequences may alter protein expression through differential mRNA degradation, a regulatory mechanism that may allow adaptation to environmental conditions, including those encountered by M. tuberculosis during infection.
One of the most compelling reasons to look at these proteins is that antibiotics in general work by seeking out and killing actively growing bacteria. It has been found that these proteins are responsible for arresting the growth of TB bacteria and enabling them to lie dormant. If we can get dormant TB bacteria to grow, this may make TB more susceptible to current antibiotic treatment.” Because MazF proteins are present in a range of mycobacteria, the research findings will be applicable to other diseases, including bovine tuberculosis and Johne’s disease in cattle, caused by Mycobacterium avium subspecies paratuberculosis. “The future success in searching for new TB drug treatments will be based on understanding of the biology, dormancy and persistence of the tuberculosis bacterium, In targeting research towards the toxin-antitoxin proteins and the regulation of their genes.
