Whole genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) is still in its infancy, with less than 50 studies published prior to 2015. Nonetheless, WGS is a powerful tool that will revolutionize tuberculosis (TB) research and TB care in three key areas:
Enhancing our understanding of MTB transmission dynamics and outbreak investigation
For the identification and characterization of TB outbreaks, WGS has a far greater resolution than MIRU-VNTR, the current gold standard genotyping method, which only analyzes a small part of the MTB genome. Insights gained could improve the design of infection control and outbreak investigation and advance interventions for latent TB.
Deciphering the emergence, role of epistatsis, and transmission of drug resistant TB
WGS provides a comprehensive record of all single nucleotide polymorphisms (SNPs), inserts and deletions in the MTB genome, producing a far greater amount of information than the current line probe assays that only target the most frequent resistance-conferring mutations for a limited number of drugs. WGS is therefore expected to result in radical improvements in diagnosis and management of drug resistant TB.
Generating new insights into the adaptation and evolution of MTB under therapeutic pressure for drug sensitive or drug resistant TB
Studying within‐host MTB pathogen adaptation and diversity WGS can link epidemiology to pathogen biology. As such, WGS could challenge long-standing dogma’s and generate new hypotheses regarding the pathogenic and virulence mechanisms of MTB. We expect this to result in insights that will aid in the identification of novel drug targets.