Selection for Antibiotic Production

Abstract

Antibiotic-producing microorganisms can gain a selective advantage by inhibiting nearby competing species. However, despite their genetic potential, natural isolates often make only small amounts of antibiotics and laboratory evolution can lead to loss rather than enhancement of antibiotic production. We sought to understand selection for antibiotic production in natural and engineered ecosystems. We show that, due to competition with antibiotic resistant cheater cells, increased levels of antibiotic production can actually decrease the selective advantage to producers. Competing fluorescently-labeled Escherichia coli colicin producers with non-producing resistant and sensitive strains on solid media, we found that while producer colonies can greatly benefit from the inhibition of nearby sensitive colonies, this benefit is shared with resistant colonies growing in their vicinity. Experimentally varying the amount of production shows a peak in selection for producers, reflecting a trade-off between benefit gained by inhibiting sensitive competitors and loss due to an increased contribution to resistant cheater colonies. A simple model, which accounts for such local competitive and inhibitory interactions, recapitulates the finding that the advantage of producers varies non-monotonically with the amount of production. These results help explain the low level of antibiotic production observed for natural species, and can help direct laboratory evolution experiments selecting for increased or novel production of antibiotics.