Author Correction: Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.

In the version of this Article originally published, the following sentence was missing from the Acknowledgements: "R.E.B. is an EPSRC Healthcare Technologies Impact Fellow EP/N033671/1; I.G. is funded by ERC Consolidator grant 647292 MathModExp; A.J.P.B., N.A.R.G. and A.T. were funded by BBSRC grant BB/F00513X/1; K.H., I.G., S.N. and E.C. were funded by BBSRC grant BB/F005210/2." This text has now been added.

Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.

Microbes rarely exist in isolation, rather, they form intricate multi-species communities that colonize our bodies and inserted medical devices. However, the efficacy of antimicrobials is measured in clinical laboratories exclusively using microbial monocultures. Here, to determine how multi-species interactions mediate selection for resistance during antibiotic treatment, particularly following drug withdrawal, we study a laboratory community consisting of two microbial pathogens. Single-species dose responses are a poor predictor of community dynamics during treatment so, to better understand those dynamics, we introduce the concept of a dose-response mosaic, a multi-dimensional map that indicates how species' abundance is affected by changes in abiotic conditions. We study the dose-response mosaic of a two-species community with a 'Gene × Gene × Environment × Environment' ecological interaction whereby Candida glabrata, which is resistant to the antifungal drug fluconazole, competes for survival with Candida albicans, which is susceptible to fluconazole. The mosaic comprises several zones that delineate abiotic conditions where each species dominates. Zones are separated by loci of bifurcations and tipping points that identify what environmental changes can trigger the loss of either species. Observations of the laboratory communities corroborated theory, showing that changes in both antibiotic concentration and nutrient availability can push populations beyond tipping points, thus creating irreversible shifts in community composition from drug-sensitive to drug-resistant species. This has an important consequence: resistant species can increase in frequency even if an antibiotic is withdrawn because, unwittingly, a tipping point was passed during treatment.

The form of a trade-off determines the response to competition.

Understanding how populations and communities respond to competition is a central concern of ecology. A seminal theoretical solution first formalised by Levins (and re-derived in multiple fields) showed that, in theory, the form of a trade-off should determine the outcome of competition. While this has become a central postulate in ecology it has evaded experimental verification, not least because of substantial technical obstacles. We here solve the experimental problems by employing synthetic ecology. We engineer strains of Escherichia coli with fixed resource allocations enabling accurate measurement of trade-off shapes between bacterial survival and multiplication in multiple environments. A mathematical chemostat model predicts different, and experimentally verified, trajectories of gene frequency changes as a function of condition-specific trade-offs. The results support Levins' postulate and demonstrates that otherwise paradoxical alternative outcomes witnessed in subtly different conditions are predictable.

Cross-organizational collaboration supported by Augmented Reality.

This paper presents a study where Augmented Reality (AR) technology has been used as a tool for supporting collaboration between the rescue services, the police and military personnel in a crisis management scenario. There are few studies on how AR systems should be designed to improve cooperation between actors from different organizations while at the same time supporting individual needs. In the present study, an AR system was utilized for supporting joint planning tasks by providing organization specific views of a shared map. The study involved a simulated emergency event conducted in close to real settings with representatives from the organizations for which the system is developed. As a baseline, a series of trials without the AR system was carried out. Results show that the users were positive toward the AR system and would like to use it in real work. They also experience some performance benefits of using the AR system compared to their traditional tools. Finally, the problem of designing for collaborative work as well as the benefits of using an iterative design processes is discussed.

Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that the observed diversity resembled results obtained in experimental evolution studies. Whatever the mechanisms leading to diversity, our results have strong medical implications in terms of the need for more extensive isolate testing before deciding on antibiotic therapies.

International river basin management under the EU water framework directive: an assessment of cooperation and water quality in the Baltic Sea Drainage Basin.

We address issues connected with international river basin management and the EU Water Framework Directive (WFD). By creating a register of River Basin Districts established under the WFD, we show that the number and area of international River Basin Districts are significant. Further, we present an assessment of international cooperation and water quality in 14 international river basins in the Baltic Sea Drainage Basin. Our results indicate that the WFD is a push forward for international river basin management in the region. However the WFD in general, and the principle of river basin management in particular, may be hard to implement in river basins shared between EU Member States and countries outside the EU. According to the study, Vistula, Pregola, and Nemunas appear to be the international basins within the Baltic Sea Drainage Basin in greatest need of intensified cooperation with regard to the state of the water quality.