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Background and objectives Slowing the spread of antimicrobial resistance is urgent if we are to continue treating infectious diseases successfully. There is increasing evidence microbial interactions between and within species are significant drivers of resistance. On one hand, cross-protection by resistant genotypes can shelter susceptible microbes from the adverse effects of antibiotics, reducing the advantage of resistance. On the other hand, antibiotic-mediated killing of susceptible genotypes can alleviate competition and allow resistant strains to thrive (competitive release). Here, by observing interactions both within and between species in microbial communities sampled from humans, we investigate the potential role for cross-protection and competitive release in driving the spread of ampicillin resistance in the ubiquitous gut commensal and opportunistic pathogen Escherichia coli. Methodology Using anaerobic gut microcosms comprising E.coli embedded within gut microbiota sampled from humans, we tested for cross-protection and competitive release both within and between species in response to the clinically important beta-lactam antibiotic ampicillin. Results While cross-protection gave an advantage to antibiotic-susceptible E.coli in standard laboratory conditions (well-mixed LB medium), competitive release instead drove the spread of antibiotic-resistant E.coli in gut microcosms (ampicillin boosted growth of resistant bacteria in the presence of susceptible strains). Conclusions and implications Competition between resistant strains and other members of the gut microbiota can restrict the spread of ampicillin resistance. If antibiotic therapy alleviates competition with resident microbes by killing susceptible strains, as here, microbiota-based interventions that restore competition could be a key for slowing the spread of resistance. Lay Summary Slowing the spread of global antibiotic resistance is an urgent task. In this paper, we ask how interactions between microbial species drive the spread of resistance. We show that antibiotic killing of susceptible microbes can free up resources for resistant microbes and allow them to thrive. Therefore, we should consider microbes in light of their social interactions to understand the spread of resistance. [ABSTRACT FROM AUTHOR]

Some microbial public goods can provide both individual and community-wide benefits, and are open to exploitation by non-producing species. One such example is the production of metal-detoxifying siderophores. Here, we investigate whether conflicting selection pressures on siderophore production by heavy metals - a detoxifying effect of siderophores, and exploitation of this detoxifying effect - result in a net increase or decrease. We show that the proportion of siderophore-producing taxa increases along a natural heavy metal gradient. A causal link between metal contamination and siderophore production was subsequently demonstrated in a microcosm experiment in compost, in which we observed changes in community composition towards taxa that produce relatively more siderophores following copper contamination. We confirmed the selective benefit of siderophores by showing that taxa producing large amounts of siderophore suffered less growth inhibition in toxic copper. Our results suggest that ecological selection will favour siderophore-mediated decontamination, with important consequences for potential remediation strategies. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. This has led to the suggestion that virulence is a costly attribute in chronic infections. However, previous reports suggest that overproducing (OP) virulent pathotypes can coexist with non-producing mutants in the CF lung for many years. The consequences of such within-patient phenotypic diversity for the success of this pathogen are not fully understood. Here, we provide in-depth quantification of within-host variation in the production of three virulence associated secretions in the Liverpool cystic fibrosis epidemic strain of P. aeruginosa, and investgate the effect of this phenotypic variation on virulence in acute infections of an insect host model. Results: Within-patient variation was present for all three secretions (pyoverdine, pyocyanin and LasA protease). In two out of three patients sampled, OP isolates coexisted with under-producing mutants. In the third patient, all 39 isolates were under-producers of all three secretions relative to the transmissible ancestor LESB58. Finally, this phenotypic variation translated into variation in virulence in an insect host model. Conclusions: Within population variation in the production of P. aeruginosa virulence-associated secretions can lead to high virulence sub-populations persisting in patients with chronic CF infections. [ABSTRACT FROM AUTHOR]

Transposable temperate phages randomly insert into bacterial genomes, providing increased supply and altered spectra of mutations available to selection, thus opening alternative evolutionary trajectories. Transposable phages accelerate bacterial adaptation to new environments, but their effect on adaptation to the social environment is unclear. Using experimental evolution of Pseudomonas aeruginosa in iron-limited and iron-rich environments, where the cost of producing cooperative iron-chelating siderophores is high and low, respectively, we show that transposable phages promote divergence into extreme siderophore production phenotypes. Iron-limited populations with transposable phages evolved siderophore overproducing clones alongside siderophore non-producing cheats. Low siderophore production was associated with parallel mutations in pvd genes, encoding pyoverdine biosynthesis, and pqs genes, encoding quinolone signalling, while high siderophore production was associated with parallel mutations in phenazine-associated gene clusters. Notably, some of these parallel mutations were caused by phage insertional inactivation. These data suggest that transposable phages, which are widespread in microbial communities, can mediate the evolutionary divergence of social strategies.

The structure of microbial communities is key to their functionality. However, this structure is likely to be influenced by adaptive genetic change in members of the community, which can occur over a matter of days. Changes in community structure can in turn influence the evolutionary trajectories of species within the community, further altering community structure. Microbial communities provide evidence for this interplay between rapid evolution and community structure. To date, studies are primarily limited to simple in vitro systems, but we suggest similar processes are inevitably operating in both natural and derived communities, which are important for biotechnology., (Copyright © 2013 Elsevier Ltd. All rights reserved.)