Abstract
Bacteria commonly live in dense and genetically diverse communities associated with surfaces. In these communities, competition for resources and space is intense, and yet we understand little of how this affects the spread of antibiotic-resistant strains. Here, we study interactions between antibiotic-resistant and susceptible strains using in vitro competition experiments in the opportunistic pathogen Pseudomonas aeruginosa and in silico simulations. Selection for intracellular resistance to streptomycin is very strong in colonies, such that resistance is favoured at very low antibiotic doses. In contrast, selection for extracellular resistance to carbenicillin is weak in colonies, and high doses of antibiotic are required to select for resistance. Manipulating the density and spatial structure of colonies reveals that this difference is partly explained by the fact that the local degradation of carbenicillin by β-lactamase-secreting cells protects neighbouring sensitive cells from carbenicillin. In addition, we discover a second unexpected effect: the inducible elongation of cells in response to carbenicillin allows sensitive cells to better compete for the rapidly growing colony edge. These combined effects mean that antibiotic treatment can select against antibiotic-resistant strains, raising the possibility of treatment regimes that suppress sensitive strains while limiting the rise of antibiotic resistance. We argue that the detailed study of bacterial interactions will be fundamental to understanding and overcoming antibiotic resistance.
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Acknowledgements
We thank Christopher Thomas for kindly providing plasmids. IF and WPJS received funding from the Systems Biology Doctoral Training Centre, funded by the EPSRC (grant number EP/G03706X/1). SM was supported by a Marie Curie Intra-European Fellowship and an Ambizione grant from the Swiss National Science Foundation. ASM is supported by a Miguel Servet fellowship from the Instituto de Salud Carlos III (MS15/00012) co-financed by the European Social Fund and The European Development Regional Fund “A way to achieve Europe” (ERDF). KRF was supported by European Research Council Grant 242670 and a grant from the Calleva Research Centre for Evolution and Human Science (Magdalen College, Oxford). RCM was funded by the Royal Society, European Research Council grant 281591, and Wellcome Trust Grant 106918/Z/15/Z.
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Frost, I., Smith, W.P.J., Mitri, S. et al. Cooperation, competition and antibiotic resistance in bacterial colonies. ISME J 12, 1582–1593 (2018). https://doi.org/10.1038/s41396-018-0090-4
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DOI: https://doi.org/10.1038/s41396-018-0090-4
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