Stealth tactics of bacteria revealed

WE ARE now privy to the ways bacteria outsmart antibiotics, thanks to a technique which measures the evolution of antibiotic resistance.

A team led by Erdal Toprak and Adrian Veres at Harvard University developed the "morbidostat", a device that constantly monitors the growth of bacteria in the presence of an antibiotic, increasing the concentration of the drug as the bacteria evolve resistance.

Using the morbidostat, the team investigated how Escherichia coli responded to three different antibiotics over 25 days.

Levels of resistance increased for all three drugs. However, resistance to chloramphenicol and doxycycline developed smoothly over time, whereas resistance to trimethoprim happened in discrete steps.

The team sequenced the genome of E. coli from the final stage of the experiment. Bacteria resistant to chloramphenicol and doxycycline had a large number of changes all over their genome, suggesting that lots of small mutations outsmart the drugs. For trimethoprim resistance, most changes took place in just one gene. The bacteria had to wait for mutations to occur in this small area, which explains why resistance evolved in stages.

Further sequencing revealed the same mutations occurring in the same order in every trimethoprim-resistant population (Nature Genetics, DOI: 10.1038/ng.1034). Knowing about these pathways of resistance could help to find drug doses to minimise resistance.

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