SETAC Nantes 2016

Another guest post, this time by Isobel Stanton, a PhD student who started work with Will Gaze October last year, co-funded by BBSRC and the pharmaceutical company AstraZeneca Global Environment (co-supervised by Prof Jason Snape). (See here for an overview of some of the work that the University of Exeter does in partnership with AstraZeneca.) She is currently investigating selection for antibiotic resistance in complex microbial communities at very low (environmentally relevant) concentrations of antibiotics. Due to the regulatory interest under the Water Framework Directive, macrolides are being used as a case study. Here goes:

Last month Will, Aimee and I visited Nantes, France for the STEAC Europe 26th Annual Meeting: Environmental contaminants from land to sea: continuities and interface in environmental toxicology and chemistry. We arrived in Nantes on Sunday 22nd May and had some time to explore the city before the opening ceremony that evening. We visited the Cathedral Saint-Peter-and-Saint-Paul, the Château des ducs de Bretagne and Les Machines De L’île Nantes. Unfortunately, we arrived too late and missed Le grand éléphant moving (https://www.youtube.com/watch?v=MrTnYOWi1RI).

We all presented in the session titled “Antibiotics and Antibiotic Resistance in the Environment: Ecological Fate and Effects, Resistance Development and Implications for Human Health.” Will and Aimee gave platform presentations; Will talking about co-selection for AMR by biocides and Aimee spoke about her work looking into selection for AMR in the environment. I presented the work I’ve undertaken since starting my PhD, also on selection for AMR in the environment, as a poster presentation. The other sessions had a much more regulatory focus than our work but it was still a good insight into the other side of the industry.abcOur trip was unfortunately cut short and we had to miss the last day of the conference to make sure we were able to get out of the city (French strikes!). We managed to arrive at the airport hours early, to a scene which looked like the beginning of an apocalypse movie (standstill traffic, cars parked on verges, people trekking with suitcases and the odd casual fire), and ended up being delayed by four hours due to air traffic control strikes). Twelve hours later we arrived back in Cornwall – much more peaceful!nantes2

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Microbial water quality All-Party Parliamentary Group meeting at Westminster

A guest post Will Gaze’s student Anne Leonard:

Last Monday, 23rd May 2016, I was invited to attend an All-Party Parliamentary Group (APPG) at the Houses of Parliament in Westminster, London. The purpose of this meeting was to discuss the Environment Agency ‘Spill Frequency Trigger Permitting’ consultation, which questions the need to implement a limit on the number of times water companies are allowed to discharge untreated sewage into sensitive waters, such as bathing beaches and shellfish waters.

The majority of the UK’s sewers are combined, collecting sewage and grey water from people’s homes and industry as well as storm water from roads and roofs. During periods of wet weather, large volumes of wastewater enter these combined sewers and exceed their capacity. Combined sewer overflows (CSOs) – are used to release this mixture of untreated sewage and storm water directly into the environment, so that raw sewage does not back up into homes and streets. Raw sewage contains numerous disease-causing microorganisms (bacteria, viruses, protozoans, etc.), which can make people ill when they come into contact with them.

In accordance with the European Bathing Water Directive and the Water Framework Directive, bathing and shellfish waters are regularly tested for the presence of sewage during the bathing season (mid-May to the end of September). However, evidence suggests that the sampling regime used only detects 11% of CSO spills, and bathers may still be exposed to bathing waters contaminated by raw sewage.

Member of Parliament, Steve Double, chaired the meeting, which was attended by MPs, representatives from NGOs like Surfers Against Sewage and the Marine Conservation Society, water companies, the Environment Agency, the shellfish industry, and the watersports sector. Speaking to this room of experts, I presented the results of three studies that I have been working on with Dr Will Gaze and Dr Ruth Garside on the threat that bacteria in coastal waters pose to human health:

  1. Participants needed for new health survey (https://vimeo.com/97107227 )
  2. Are we exposed to antibiotic resistance in coastal waters? (https://vimeo.com/122534069)
  3. Beach bum survey (http://www.ecehh.org/news/beach-bums/)

Since the meeting last week, MPs have confirmed that they will be writing to the Environment Agency, urging them to enforce tighter legal thresholds on CSOs from systems that have already been designed or recently updated to reduce the frequency of spills to just 3 per bathing season.large group westminster

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Visit to the Netherlands Institute of Ecology, Wageningen

NIOO2Last week I visited past colleague and collaborator Paolina Garbeva at the Netherlands Institute of Ecology NIOO in Wageningen where I worked as a postdoc between 2009 and 2011. Paolina is an expert in the secondary metabolites (especially the volatile ones) of soil bacteria and fungi. It was great to hear about the research in her group, sat in the typical blistering Dutch sun on the roof terrace of the groundbreaking eco-building. I also gave a talk about our seaweed antimicrobial work. Paolina and I plan to write papers and proposals in the near future, hopefully more on that soon on the blog!

Michiel

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Paper out: A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

MyxofruitingbodyJust out in the ISME journal, a paper on my favourite bacterium, Myxococcus xanthus. I did my PhD with Greg Velicer on this fascinating species which builds beautiful multicellular fruiting bodies that can be seen with the naked eye (click on my personal page underneath the page header for a publication list with pdf downloads, including a review paper). I thought it would be nice to return to the strains I isolated back then and do some population genomics. It turned out to be an interesting project although not without significant obstacles; papers are a bit like sausages, they can be very enjoyable but you do not want to necessarily know how they were made. Anyway, from the Abstract:

The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16×16 centimetre-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter.  We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring MultiLocus Sequence Type (MLST) clades in order to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination.

Fig_1-page-001Above a nice Figure made by first author Seb Wielgoss that shows the location in the centimeter-scale plot the representatives of the two clades (genotypes) were isolated from (A) and a core genome phylogenetic tree clearly showing that the two clades are distinct, with limited within-clade diversity (B). For instance, strains A31 and A34 do not have a single SNP difference across their aligned conserved sequence of 7.6 Mb! For the homologous recombination analysis, co-author Xavier Didelot employed the FineStructure software (for a nice explanation on how this works see here), which has also been used in a high profile study on the genetic ancestry of the British population. The figure below shows a co-ancestry matrix on the left, with warmer colours representing higher percentages of recombinational copying from one genome to another. Genomes belonging to the same FineStructure population are connected by a vertical branch in the tree on the right, with the rest of the tree indicating inferred relationships between seven identified populations. The dark blue colours indicate negligible (<0.01%), homologous recombination between Clades I (populations 5-7) and V (populations 1-4). To my knowledge, this is only the third time a barrier to recombination between bacteria from the same population has been shown, and the first for a soil bacterium.

Fig_2-page-001Actually the main reason I wanted to sequence these genomes is to find out how different strains are able to recognize kin from non-kin. It is likely that Myxococcus meets other distinct strains, as many types can be found on a scale of even centimeters. In another paper, it could be shown that genetically distinct swarms were generally very bad at building fruiting bodies together. That scenario might actually not even be very relevant, as mixing of distinct cells is most likely when they are actively swarming. In the same paper however, it could be shown that swarms did not mix upon encounter, and that there thus must be some genetic mechanism whereby cells can discriminate self from non-self:Presentation1

By sequencing a set of genomes of strains that can either mix or not, genetic differences that consistently differ between such sets can be identified. Indeed, a large genomic tract was located that consistently differed with swarming compatibility. Again Seb made a really nice Figure to visualize these differences in gene content. First a phylogeny based on gene content variation in the variable region (A). Clusters match compatibility type (CT) groupings derived from social swarm merger assays. On the right a visual representation of the absence (black) and presence of single (light red) and multicopy (dark red) genes in the focal region. The proof in the pudding was a strain (A92) that could not mix with strains that it was otherwise genomically closely related to that was identical in this genomic tract with other strains it could mix with.Fig_4-page-001This study was explorative in nature; you never know what you are going to find when sequencing new genomes. So there were a number of other significant findings (having multiple interesting findings perhaps paradoxically made the manuscript a harder sell…). For instance, we could show that changes in gene content (in the ‘accessory genome’) were much more prevalent than mutational changes (in the ‘core genome’). This finding actually was the inspiration of a recent Opinion paper on accessory genome evolution, see this recent post. I had hoped that differences on the DNA level would shed light on ecological differences between strains that could explain their coexistence but that proved very difficult as most genes were of unknown function. We did find massive differences in CRISPR-Cas systems though (these results ended up mainly in the supplemental material). The advance online publication is freely available from the journal’s website:

Wielgoss, Sébastien, et al. “A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus.” The ISME Journal (2016).

Michiel

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Marcus Wallenberg Symposium Stockholm

academy

The Royal Swedish Academy of Sciences. Thanks to Uli for the artistic sun shot.

I think it’s pretty common for every scientist to dream at least once about winning a Nobel Prize for their research. While sadly the vast majority of us will always remain underappreciated by the Royal Swedish Academy of Sciences, you could argue the next best thing would be to be asked to present your research at the Academy. In which case, the Coastal Pathogens group is doing pretty well.

Will, Uli and I attended the Marcus Wallenberg Symposium entitled ‘The role of metals and biocides in the selection of antibiotic resistant bacteria’ at the prestigious Kungliga Vetenskaps-Akademien in Stockholm from the 15th to 16th of March. As an invited speaker, Will presented his impressive back catalogue of work on quaternary ammonium compounds and co-selection for antibiotic resistance (which he has been working on with Lihong for several years, and more recently – myself), alongside big names like Dan Andersson (who’s 2011 paper on minimal selective concentrations was the inspiration for my PhD) and Joakim Larsson (well known for his work in pharmaceutical factory effluents). Uli also presented some of his work from his PhD under Bart Smets on bacterial community permissiveness (the ability to take up a plasmid) under metal stress.There was a good balance of clinical (Maillard, Ingmer, Perron, Melhus) and environmental (Will, Graham, Brandt, Larsson) based research investigating co-selection of antibiotic resistance. The symposium was open to attendance to the public, so the varied audience (academia, industry, healthcare etc) had some interesting comments and questions in the concluding round table discussion, particularly what the next steps might be in tackling this issue might be. The consensus seemed to be that without more concrete evidence to show metals and biocides do co-select for antibiotic resistance, stakeholders would remain unwilling to undertake the massive mitigation steps that would be required and the financial burden that would follow.

will

Will presenting his talk: “An environmental perspective of the role of quaternary ammonium compounds in co-selection for antibiotic resistance.” Thanks to Uli for the pic.

round table

Round Table Discussion. Left to Right: Christopher Rensing, Karl Perron, Teresa Coque, David Graham, Kristian Brandt, Dan Andersson, Will Gaze, Mats Tysklind, Åsa Melhus, Hanne Ingmer. Chair: Joakim Larsson

Stockholm itself (the little I managed to see of the Old Town, or ‘Gamla Stan’) was simultaneously quaint and charming but also impressive, riddled with narrow cobbled streets but peppered with enormous majestic buildings like the cathedral and the Nobel Prize Museum. From the latter I did live the dream and get my very own Nobel Prize medal. Unfortunately it was only a chocolate one… but it was delicious.

Aimee

nobel prize museum

Nobel Prize Museum

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Group Update

A very long while without a post on this blog, so high time for an update. This blog is mainly written by me with occasional (very good!) guest posts by members of Will Gaze‘s group (see e.g. here). It features short posts on papers that have come out, as well as teaching and outreach activities, places we’ve been, people joining the lab or more general musings about microbiology or science. For information on who is working with myself or with Will, please see the European Centre for Environment and Human Health People gallery. For now I just wanted to introduce the students that are working with me at the moment:students

l to r: Michiel Vos, Amy McLeman, Lise Jensen, Michael Tadesse and Andy Dickinson

Amy McLeman has been working with me as a technician for a while, went off to another position but of course could not resist coming back. She is working on a BBSRC-funded seaweed antimicrobial metabolomics project with Dr. Ruth Airs at the Plymouth Marine Laboratory and myself over the summer before starting a PhD position with Prof ffrench Constant. Lise Jensen is an MSc student visiting from the University of Copenhagen (Helsingor) supervised by Prof. Mathias Middelboe who was an academic visitor with us last summer. She is also interested in seaweeds, especially their potential to ward of fish pathogenic bacteria. Next, BSc. in Medical Sciences student Mickey Tadesse is spending his third year doing a lab project, also on seaweed antimicrobials. Finally, MSc by Research student Andy Dickinson is working on co-selection of antibiotic resistance in heavy metal-contaminated pond sediment in collaboration with Britt Koskella and Richard Jones. I hope to be able to persuade these guys to write guest blog posts on their projects soon!

Michiel

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paper out: Adaptation in Natural Microbial Populations

A review paper by Britt Koskella (now at Berkeley) and myself recently came out ‘adaptation in natural populations’; I have lazily copied the Abstract below:

Although their diversity greatly exceeds that of plants and animals, microbial organisms have historically received less attention in ecology and evolutionary biology research. This knowledge gap is rapidly closing, owing to recent technological advances and an increasing appreciation for the role microbes play in shaping ecosystems and human health. In this review, we examine when and how the process and patterns of bacterial adaptation might fundamentally differ from those of macrobes, highlight methods used to measure adaptation in natural microbial populations, and discuss the importance of examining bacterial adaptation across multiple scales. We emphasize the need to consider the scales of adaptation as continua, in which the genetic makeup of bacteria blur boundaries between populations, species, and communities and with them concepts of ecological and evolutionary time. Finally, we examine current directions of the field as we move beyond the stamp-collecting phase and toward a better understanding of microbial adaptation in nature.

Koskella, Britt L., and Michiel Vos. “Adaptation in Natural Microbial Populations.” Annual Review of Ecology, Evolution, and Systematics 46, no. 1 (2015). cough

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