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Persistence Pays for Bacteria Too!

© Neal Rolfe Chamberlain

When I was in graduate school the common saying while we were conducting experiments was, "persistence pays". We used that saying often because many times our experiments did not work as they were supposed to or they took us to different conclusions than we originally thought we would get. Intelligence is important in research however, the willingness to go in day after frustrating day and work to get answers requires for the most part persistence.

Almost 60 years ago (W.B. Bigger, 1944, Lancet, p. 497-500) researchers found that bacteria can be persistent too. They discovered that when bacteria are given high doses of antibiotics almost every bacterial cell died within 6 hours of exposure. Only a very small percentage survived. These persistent bacteria when grown up without antibiotic and then given the same antibiotic all over again once again died off in large numbers. This persistence phenomenon was not due to the bacteria acquiring some sort of resistance to the antibiotic. If they were resistant when exposed to the antibiotic a second time only a very few of the bacteria would die. Rather every time the antibiotic was given 99.999 percent of the bacterial cells were killed by the antibiotic. Only 0.0001 percent survived but this very small percentage of bacterial cells consistently survived experiment after experiment.

For many years no one thought any more about this persistence phenomenon. Many thought it was some experimental artifact that could be explained by the fact that the antibiotic used in those experiments only killed actively growing bacteria and the bacteria they were treating stopped growing. However, recently other investigators (K. Lewis et. al.) have used antibiotics that do not require actively growing bacteria to kill (quinolones). Even using quinolones they found these pesky persistent bacteria. Not nearly as many bacterial cells but they were persistent just the same.

A recent journal article by N.Q. Balaban et. al. (www.sciencexpress.org/12 August 2004/Page 1/10.1126/science.1099390) demonstrated how these bacteria resist killing by antibiotics. They were able to grow bacteria on specially grooved slides and filmed the bacteria before, during and after antibiotic treatment. They could follow several hundred different bacteria cells at a time. When they added an antibiotic called ampicillin they killed almost all of the bacteria on the slide. However, one persistent bacterial cell grew very slowly before antibiotic treatment and when treated with ampicillin did not die. When the antibiotic was taken away that one cell started to grow again. To see this for yourself click here to get to the supporting online material. The S2 movie is the better one of the two movies.

So it does appear that some persistent bacteria grow slower. They are called