Researchers have identified a host of genetic mutations, including some novel ones, in the genomes of tuberculosis (TB)-causing bacteria that have developed resistance to multiple antibiotics1. This knowledge will shed light on the molecular mechanisms of drug resistance and assist in the design of novel antibiotics.
The emergence and spread of drug-resistant TB-causing bacteria is of global concern. Prolonged and expensive treatments are needed for patients with drug-resistant bacteria. During such treatments, the antibiotics unleash their toxic effects and further increase the risks of resistance.
To understand the mechanisms of drug resistance, an international research team, including researchers from the Foundation for Medical Research, Mumbai in India, sequenced the genomes of TB-causing bacteria isolated from patients living in 30 countries. They homed in on a number of mutations in the genes that created drug-resistant bacteria.
Of all the drug-resistant bacteria, 31.2% were resistant to at least one drug, 15.1% were multidrug-resistant and 4.3% were extensively resistant to drugs.
The drug-resistant bacteria harboured a mutation in a gene that codes for a specific protein involved in transporting antibiotics across the membrane – a potent mechanism to render the antibiotics ineffective.
Besides genetic mutations due to changes in single bases in genes, the scientists also identified genetic mutations such as insertion and deletion of bases in specific genes, predominantly genes that encode enzymes known to metabolise drugs.
Such insertion and deletion of bases in genes will be potentially useful for designing molecular tests for detecting resistance, the researchers say.