Genomics offers new handle on TB antibiotic resistance

10 September 2013

Research has revealed a high degree of genomic complexity underlying antibiotic resistant tuberculosis (TB).
 
Globally there are approaching nine million cases of tuberculosis annually, and over a million deaths. Although the number of cases in developed countries is low (around 9,000 per year in the UK), the disease remains a significant public health issue around the world, thanks to the emergence and spread of antibiotic resistant strains of the infectious agent, Mycobacterium tuberculosis. Recently, new strains have been identified that are resistant to all known antibiotics. How to control the spread of these most dangerous mycobacteria is a critical issue.
 
Findings published in the journal Nature Genetics provides support in the form of a catalogue of resistance-associated genetic variants found in M. tuberculosis genomes and their evolutionary pathways.  Some M. tuberculosis strains are known to be much more prone to develop resistance than others. Now genetic markers for resistant and resistance-prone strains have been deciphered.
 
Besides identifying novel resistance-associated mutations – some with as yet unknown functions - the new research showed very complex relationships between different genetically determined resistance mechanisms. Some variants increased the rate at which the mycobacteria mutate, making the development of resistance associated mutations more likely, or influenced other mutations, making them more beneficial to the mycobacterial strain.

The knowledge should help identify patients with M. tuberculosis strains at the greatest risk of developing multiple or complete drug resistance, helping with control. Ultimately it may also open avenues of research into potential new antibiotics to treat TB. 

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