title: Socially mediated induction and suppression of antibiosis during bacterial coexistence.
abstract: Despite their importance for humans, there is little consensus on the function of antibiotics in nature for the bacteria that produce them. Classical explanations suggest that bacteria use antibiotics as weapons to kill or inhibit competitors, whereas a recent alternative hypothesis states that antibiotics are signals that coordinate cooperative social interactions between coexisting bacteria. Here we distinguish these hypotheses in the prolific antibiotic-producing genus Streptomyces and provide strong evidence that antibiotics are weapons whose expression is significantly influenced by social and competitive interactions between competing strains. We show that cells induce facultative responses to cues produced by competitors by (i) increasing their own antibiotic production, thereby decreasing costs associated with constitutive synthesis of these expensive products, and (ii) by suppressing antibiotic production in competitors, thereby reducing direct threats to themselves. These results thus show that although antibiotic production is profoundly social, it is emphatically not cooperative. Using computer simulations, we next show that these facultative strategies can facilitate the maintenance of biodiversity in a community context by converting lethal interactions between neighboring colonies to neutral interactions where neither strain excludes the other. Thus, just as bacteriocins can lead to increased diversity via rock-paper-scissors dynamics, so too can antibiotics via elicitation and suppression. Our results reveal that social interactions are crucial for understanding antibiosis and bacterial community dynamics, and highlight the potential of interbacterial interactions for novel drug discovery by eliciting pathways that mediate interference competition.
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands; Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, United Kingdom;
authors.forename: Monica I
authors.initials: MI
authors.lastname: Abrudan
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands;
authors.forename: Fokko
authors.initials: F
authors.lastname: Smakman
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands; Faculty of Mathematics and Natural Sciences, University of Groningen, 9747 AG Groningen, The Netherlands;
authors.forename: Ard Jan
authors.initials: AJ
authors.lastname: Grimbergen
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands;
authors.forename: Sanne
authors.initials: S
authors.lastname: Westhoff
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands; Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, United Kingdom;
authors.forename: Eric L
authors.initials: EL
authors.lastname: Miller
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands; Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), 6708 PB Wageningen, The Netherlands.
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
authors.affiliation: Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands; d.e.rozen@biology.leidenuniv.nl.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Rozen
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D013302:Streptomyces / Q000378:metabolism / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Streptomyces; antibiotics; competition sensing; microbial ecology; sociomicrobiology