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Science of sleep.
The scientists used fluorescent proteins--green and red in these images--to determine whether E. coli bacteria were active.

Gefen et al., PNAS 105 (22 April 2008)

Sleep Deprivation for Germs

Most antibiotics kill only microbes that are growing and multiplying, leaving untouched a select few that are hibernating. A new study suggests that a dose of the right nutrients can awaken these bacteria for just long enough to kill them with antibiotics. If the strategy works in humans, it might provide a more effective way to treat persistent diseases such as tuberculosis and urinary-tract infections.

During infections, bacteria may slow or stop their growth. They enter this "stationary" state when nutrients are scarce, which occurs often in an infected host. A few bacteria eventually shut down and become completely dormant. Biophysicist Nathalie Balaban and her team at Hebrew University in Jerusalem wanted to figure out what makes these bacteria tick.

To study the cycle in the lab, the team added fresh nutrients to a stationary culture of Escherichia coli bacteria. Most of the cells started growing and dividing again, as expected, making them more vulnerable to antibiotics. But a small minority became active only temporarily: The first hour and a half after fresh nutrients were added, they restarted their protein-production machinery, as if they were gearing up to start dividing. Then they shut down completely to become dormant. Once in this persistent state, they are invulnerable to antibiotics, and they can't be tempted to wake up with nutrients. During the 1.5 hours of yawning, however, they were susceptible to antibiotics, the group reports online today in the Proceedings of the National Academy of Sciences; ampicillin killed the vast majority.

This suggests that a way to prevent bacterial persistence is to give a patient a dose of the nutrient that is limiting the growth of microbes--depending on the microbe, this might be iron, zinc, or some other component--while administering an antibiotic at the same time, Balaban says.

It's an "unexpected and unusual" finding, says microbiologist Kim Lewis of Northeastern University in Boston, who also studies persistence. However, he's not sure how useful the study will prove to be. Previous studies have shown that some bacteria become completely dormant--and untreatable--as soon as they enter the stationary phase. With the strategy proposed by Balaban, bacteria that are already asleep would not be reawakened, Lewis says.