How Bacteria Persist Despite Antibiotics

Persistence pays off – for bacteria as well as people. Researchers at the Hebrew University of Jerusalem and Rockefeller University in New York have demonstrated the constant presence of antibiotic-tolerant “persistent cells” within bacteria colonies and have shown, through mathematical modeling, how these cells develop into “normal” cells following their survival of even heavy dosages of antibiotics.

The findings have consequences for development of new tactics for overcoming the common problem of resistance by bacteria to medicinal treatment.

It has been known for some time that when an antibiotic is administered to counteract a specific bacterium, not all of the bacterial cells may die. Persistent cells can remain that will reinfect the patient later – the condition we commonly refer to as relapse. What was not known was the exact nature of these persistent cells nor how they function.

In their research with E. coli bacteria, the Hebrew University and Rockefeller University researchers discovered that persistent cells are a kind of reserve population that is constantly being produced within bacteria, regardless of whether the bacteria are being attacked by an antibiotic or not. These cells are slow-growing and – apparently because of their “retarded” or “non-mature” state – are not susceptible to antibiotics.

Translating their observations into a mathematical model, the researchers have shown how these persistent cells slowly but surely continue growing until they reach a “normal” growth stage. At that point, the former persistent cells are now themselves susceptible to antibiotic attack.

The work of the researchers – Prof. Nathalie Questembert-Balaban, head of the biophysics laboratories at the HU Racah Institute of Physics; Prof. Stanislas Leibler of Rockefeller University; and his students Jack Merrin, Remy Chait and Lukasz Kowalik – appeared in a recent issue of Science magazine.

Prof. Balaban observes that if the timing could be worked out so that the persistent cells could be “hit” with antibiotics at the point that they reach a normal growth stage, then perhaps the problem of relapse could be overcome. Alternatively, perhaps further study of the nature of the persistent cells could lead to drugs that would take direct action against them in their initial state.

The discoveries by the Hebrew and Rockefeller universities scientists might also point in the direction of overcoming the problem of reoccurrence of cancer in patients who have undergone earlier, successful remission.

Slow-growing bacteria cells that are resistant to antibiotic drugs are shown in the magnified illustration at left among the other “normal” bacterial cells, and again at right showing how they have survived after the other bacterial cells have been destroyed by antibiotics. (Illustration courtesy of the Hebrew University of Jerusalem)

Hebrew University of Jerusalem