Inside Science (01.03.13)
Researchers have discovered one manner in which bacteria evade antibiotics. The study used the Mycobacterium smegmatis because it is similar to Mycobacterium tuberculosis, the bacterium that causes TB, but safer than using the TB bacterium.
The prevailing thought about the way antibiotics work is that antibiotics attack bacteria as they divide, preventing them from building cell walls. One theory maintains that bacteria contain some cells that do not divide (persister cells). Since these cells do not divide, they are not affected by drugs that attack cell division and remain unaffected.
The scientists used isoniazid, one of the first line of TB drugs, in the experiments. Isoniazid is a “pro-drug,” which means it does not work until it interacts with chemicals in the bacterial cell. The drug is switched on when it meets an enzyme known as KatG, which is produced by the cell. The researchers found that cells produced KatG in random pulses, and the drug did not work between pulses, hence cells that were not producing KatG survived. According to John McKinney of the Swiss Institute and one of the lead authors of the study, pulsing is infrequent and short-lived. The team has not been able to find a pattern in the pulsing so far. Most cells moved from birth to the next division without pulsing. This means that the drug would have to be present long enough to catch all the cells when they were pulsing in order to end the infection. If not, the surviving cells would mutate resistance.
The study, “Dynamic Persistence of Antibiotic-Stressed Mycobacteria,” was published in the journal Science, (2013; 339(6115):91-95).