Limits to compensatory adaptation and the persistence of antibiotic resistance in pathogenic bacteria

The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP7/2007-2013)/ERC grant agreement no. 281591 and from the Royal Society.Peer reviewedPublisher PD

Testing the Role of Genetic Background in Parallel Evolution Using the Comparative Experimental Evolution of Antibiotic Resistance

The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no. 281591 and from the Royal Society. V.F. was supported by an MEC Postdoctoral Fellowship from the Spanish Government (EX-2010-0958). T.V. and M.K. carried out the experimental work and analyzed experimental data with R.C.M.; V.F. constructed the phylogeny; V.F. and T.V. carried out comparative analyses; T.V. and R.C.M. prepared the manuscript and all authors contributed to designing the study.Peer reviewedPublisher PD

Identification of the Major Hydrological Threats for Two Clay Pan Wetlands in the South West of Australia

Abstract: This study presents the findings of a wetland ecohydrological model (WET-0D), used to recreate a historical water regime and predict the future water regime for two clay pan wetlands in South West Western Australia. WET-0D simulates the major hydrological fluxes through three conceptual water storages including the open water/lake, and surrounding unsaturated and saturated zones. Groundwater -soil water balance -vegetation (GSV) dynamics are modelled with plant biomass simulated as three functional vegetation groups with differing water uptake strategies and dependence on water availability. The wetland model was driven by a simple catchment water balance model, using historical climate data from the Bureau of Meteorology (BoM). To simulate the potential impact of climate change on wetland ecohydrology, statistically downscaled output from a Global Climate Model (GCM), based on the IPCC SRES A2 scenario, was used to drive the models to predict potential future water regimes. This allowed us to gain an insight of the impact of projected drying climate on the clay pan ecosystems. Although both clay pan catchments experience very similar climates, differences in the partitioning of rainfall and subsequent flow generation, due to different vegetation, soil type and topography, results in dissimilar hydrological regimes. Differences in the hydrological regimes alter the way predicted climate change affects water flux and hydroperiod (period of surface flooding of a wetland) in both clay pan systems. Historically, the modelling predicts the lake level in the North East clay pan is more dependent on overland flow, while the South West clay pan is more dependent on shallow groundwater flow from a seasonal aquifer. Under a drying climate the modelling predicts, the South West clay pan will become increasingly overland flow dependent. However, the shallow groundwater inputs to the clay pan prolong inundation by reducing the rate of seepage from the clay pan. The partial clearing of the catchment area for the South West clay pan has maximised groundwater recharge efficiency allowing maintenance of ecological water requirements under a drying climate. The North East clay pan is under greater threat due to the reliance of surface water inflow and the lack of groundwater input due to differences in catchment characteristics

Predators reduce extinction risk in noisy metapopulations

Background Spatial structure across fragmented landscapes can enhance regional population persistence by promoting local “rescue effects.” In small, vulnerable populations, where chance or random events between individuals may have disproportionately large effects on species interactions, such local processes are particularly important. However, existing theory often only describes the dynamics of metapopulations at regional scales, neglecting the role of multispecies population dynamics within habitat patches. Findings By coupling analysis across spatial scales we quantified the interaction between local scale population regulation, regional dispersal and noise processes in the dynamics of experimental host-parasitoid metapopulations. We find that increasing community complexity increases negative correlation between local population dynamics. A potential mechanism underpinning this finding was explored using a simple population dynamic model. Conclusions Our results suggest a paradox: parasitism, whilst clearly damaging to hosts at the individual level, reduces extinction risk at the population level

Environmental pleiotropy and demographic history direct adaptation under antibiotic selection

Evolutionary rescue following environmental change requires mutations permitting population growth in the new environment. If change is severe enough to prevent most of the population reproducing, rescue becomes reliant on mutations already present. If change is sustained, the fitness effects in both environments, and how they are associated-termed 'environmental pleiotropy'-may determine which alleles are ultimately favoured. A population's demographic history-its size over time-influences the variation present. Although demographic history is known to affect the probability of evolutionary rescue, how it interacts with environmental pleiotropy during severe and sustained environmental change remains unexplored. Here, we demonstrate how these factors interact during antibiotic resistance evolution, a key example of evolutionary rescue fuelled by pre-existing mutations with pleiotropic fitness effects. We combine published data with novel simulations to characterise environmental pleiotropy and its effects on resistance evolution under different demographic histories. Comparisons among resistance alleles typically revealed no correlation for fitness-i.e., neutral pleiotropy-above and below the sensitive strain's minimum inhibitory concentration. Resistance allele frequency following experimental evolution showed opposing correlations with their fitness effects in the presence and absence of antibiotic. Simulations demonstrated that effects of environmental pleiotropy on allele frequencies depended on demographic history. At the population level, the major influence of environmental pleiotropy was on mean fitness, rather than the probability of evolutionary rescue or diversity. Our work suggests that determining both environmental pleiotropy and demographic history is critical for predicting resistance evolution, and we discuss the practicalities of this during in vivo evolution

Cooperation, competition and antibiotic resistance in bacterial colonies

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

Relative impacts of key drivers on the response of the water table to a major alley farming experiment

Widespread clearing of native vegetation in Southwest Western Australia has led to land degradation associated with rising groundwater, secondary salinisation and waterlogging. Re-establishing deep-rooted perennial vegetation across parts of the landscape is one technique for managing land degradation. Alley farming is an agroforestry practice where multiple perennial tree belts are planted in alternation with traditional agricultural crops. To identify the best configuration (belt width versus alley width) for controlling rising groundwater levels and providing viable economic returns, a large scale experiment was established in 1995. The experiment contains seven different alley farming designs, each with transects of piezometers running across tree belts into adjacent alleys to monitor changes in the groundwater level. Two control piezometers were also installed in an adjacent paddock. Groundwater at the site is shallow (<3 m) and of poor quality (pH 3–5, Ec 2.1–45.9 mS cm−1) so root water uptake from the saturated zone is limited. Simple hydrograph analysis could not separate treatment effects on the water table response. Subsequent statistical analysis revealed that 20–30% of the variability in the water table data over the 12 year study period was attributable to the alley farming experiment. To futher investigate the effect of the experiment on groundwater response, additional hydrograph analysis was conducted to compare the trends in the control piezometers in relation to those located within the belts. A difference of 0.9 m was observed between the mean groundwater levels in the control piezometers and the mean levels in the perennial belt piezometers. For a mean specific yield of 0.03 m3 m−3 (standard deviation of 0.03 m3 m−3) this equates to an additional average annual water use of 27 mm yr−1 (standard deviation of 33 mm yr−1) by the perennial agroforestry system. It is concluded that declining annual rainfall is the principal control on hydrograph response at the site, whilst perennial biomass development has a lesser impact on water table depth

Vogwill Maclean metanalysis for dryad August 2014

Excel file containing all data relevant for statistical analyses

Data from: Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across 8 strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across 3 strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds

Data from: Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across 8 strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across 3 strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds