title: Bacterial charity work leads to population-wide resistance.
abstract: Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population's less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.
authors.affiliation: Howard Hughes Medical Institute, Center for BioDynamics, Boston, Massachusetts 02115, USA.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Lee
authors.forename: Michael N
authors.initials: MN
authors.lastname: Molla
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D007211:Indoles / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D009154:Mutation; D009643:Norfloxacin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D007211:Indoles; C030374:indole; D009643:Norfloxacin
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