Treating drug resistant TB could create vicious cycle

Mycobacterium tuberculosis, the microbe responsible for TB Copyright: NIAID

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The main treatment for drug-resistant tuberculosis (TB) could increase the appearance of resistant bacteria if used inappropriately, say researchers who have identified the genetic cause of this ironic twist.

Denise O’Sullivan of the University College London Medical School in the United Kingdom will present the findings today (5 April) at a meeting of the UK Society for General Microbiology.

Quinolones are antibiotics used to combat strains of the TB bacterium, Mycobacterium tuberculosis, that are resistant to conventional drugs. They kill the bacterium by chopping up its DNA.

But low doses of quinolones that do not kill the bacterium can boost the rate at which its DNA mutates up to 120-fold, increasing the chance of it evolving into a form that can resist quinolones entirely, regardless of dosage.

To find out what caused the dramatic increase in mutations, O’Sullivan looked at how quinolones affect the bacterium’s genes.

She found that when TB bacteria survive low doses of a quinolone called ciprofloxacin, they activate a system — known as the ‘SOS response’ — that repairs damaged DNA.

But as the system repairs DNA, it also often causes mutations.

Stephen Gillespie, who supervised O’Sullivan’s research, says that if the same happened in TB patients, it could lead to the emergence of bacteria that are resistant to quinolones and other anti-TB drugs.

Patients are given quinolones because the TB strain they carry is resistant to the conventional drugs. But as Gillespie points out this is often because these patients did not complete their course of conventional drugs.

The researchers say the findings underline the importance of adhering to drug prescriptions — a challenge in developing countries where poverty and a poor health infrastructure mean that patients often stop taking their pills before completing the treatment.