visit to the StrAda lab at the University of Nancy

Streptomyces producing the blue pigment actinorhodin

Last week I visited the ‘StrAda’ (Streptomyces Adaptation) lab of Pierre Leblond at the University of Nancy in France. Pierre and his colleagues, including Cyril Bontemps, have been isolating and genome-sequencing Streptomyces from very fine spatial scales which formed the basis of a good day of discussion. There are some interesting parallels between Streptomycetes and Myxobacteria: both are important components of soil communities (but also occur in marine environments), have large genomes with high GC content, partly multicellular life cycles which includes spore formation, and a rich diversity in secondary metabolites. There are many differences as well, Streptomyces for instance have linear chromosomes.  We discussed a plan to apply for a grant, combining our interests in the evolution of soil bacteria and recombination, which I hope to post about in the future. All in all a very stimulating trip, with great hosts, great discussion and some great French food as well!

Michiel

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Pipelines for bacterial evolutionary genomic analysis meeting in Bath

dsc_0223I attended a small, but very nice meeting last week at the University of Bath. The topic was the development of software to measure all important parameters in bacterial population genomics datasets. It was organized by Daniel Falush, who is very well known in the field of statistical genetics, developing methods such as STRUCTURE (used to study genomes from bacteria to humans). He has recently moved from Swansea to Bath along with Sam Sheppard and so with Ed Feil already there, this means Bath is now a world class centre of bacterial genomics. Unfortunately collaborators Adam Eyre-Walker and Xavier Didelot (see this and this recent paper) could not make it, but it was extremely useful to meet new people.

Michiel

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Altmetrics

I recently had a paper accepted and therefore dutifully registered it on the University’s Symplectic database. This forms a repository for all the publications generated by the university, which is of course a vital tool for summarizing research output (for instance for the Research Excellence Framework). It is required to upload the accepted manuscript, but as many journals do not permit uploading a pdf of the published version, usually the word file of the accepted version is submitted (which makes it a great deal less valuable, as such versions are not combined with figures in an easy-to-read journal format and miss corrections made at the proof stage). I noticed that Symplectic uses Scopus H-factor calculations, which is a shame, as this Elsevier database does a very bad job at that (even worse than Web of Science, see this old post).

For the first time, I checked some of the ‘altmetrics‘ for some of my papers. I have been sceptical about tallying the number of twitter mentions etc: if you are on a paper with lots of tweeting authors and/or in a field where people tend to be more active on twitter (e.g. computational biology), there will be a bunch of those, but in general the number seems small and biased.  The whole online interactivity surrounding publications is usually quite minimal; this must be for a large part because scientists are too busy with their own research to write more than a lazy tweet about research by other people. I do appreciate that the PLoS journals for instance give the opportunity to comment on papers but I hardly see people actually doing that. Anyway, the immediate reason for writing this brief blog post was that one of the altmetrics I noticed, was a youtube video. When clicking it, I saw to my great surprise five North American scientists, led by Dr. Laura Williams, doing an tele-conference journal club about one of my papers (briefly outlined in this blog post). A one-hour dissection of a paper by colleagues for the world to see: scary!

So far, I have only zapped through and luckily it seemed mostly positive. It was quite interesting to see that some points did not come across as well as I hoped they would do, providing an opportunity to reflect on how to better communicate findings.

Although I really should have done some more reading on altmetrics for this post, it’s social media component, albeit interesting, does not seem a very reliable indicator of research impact. There are other altmetrics that seem very promising though. For instance, just the total number of paper views or downloads could be really useful: they are much greater in number and much less time-lagged than citations, making them perhaps a more accurate proxy for interest garnered. (Of course, citations reflect other scientists having actually built on the work, whereas some of the views/downloads will be of people who after reading it might find that the paper has very little value, but still.) Our Symplectic database does list Mendeley and CiteULike reads but does not go beyond this (small) portion of total reads. As some fields have many more workers than others, and of course as older papers have had more time to accumulate views, some corrections could be applied (the same goes for citation numbers, so this is not a unique criticism). PLoS not only gives the raw numbers of paper downloads, but also a little graph on how a paper compares to others published by the same journal in the same field in the same year, which is neat. I will highlight the accepted manuscript in a next blog post as soon as it is published!

Michiel

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Paper Out: The Ecological Role of Volatile and Soluble Secondary Metabolites Produced by Soil Bacteria

First of all a very happy 2017 to all readers. It will be my new year’s resolution to update the blog more frequently (for instance, I have not blogged about really interesting visits to Prof Haiwei Luo in Hong Kong, the natural product discovery company Selcia in the UK or a talk for the Cornish Microbiological Society with our colleagues at the hospital in Truro….).

Anyway, I was fortunate enough to be invited to contribute (a little bit!) to a review paper on volatile secondary metabolites with lead author Dr. Paolina Garbeva at the Netherlands Institute of Ecology (see here for a short post on a visit last year). Paolina have a collaboration planned for this year which I am very excited about (and which will be documented on the blog). The paper in Trends in Microbiology came out just before the end of 2016, from the Abstract:

The rich diversity of secondary metabolites produced by soil bacteria has been appreciated for over a century, and advances in chemical analysis and genome sequencing continue to greatly advance our understanding of this biochemical complexity. However, we are just at the beginning of understanding the physicochemical properties of bacterial metabolites, the factors that govern their production and ecological roles. Interspecific interactions and competitor sensing are among the main biotic factors affecting the production of bacterial secondary metabolites. Many soil bacteria produce both volatile and soluble compounds. In contrast to soluble compounds, volatile organic compounds can diffuse easily through air- and gas-filled pores in the soil and likely play an important role in long-distance microbial interactions. In this review we provide an overview of the most important soluble and volatile classes of secondary metabolites produced by soil bacteria, their ecological roles, and their possible synergistic effects.

Tyc O, Song C, Dickschat JS, Vos M, Garbeva P. The Ecological Role of Volatile and Soluble Secondary Metabolites Produced by Soil Bacteria. Trends in Microbiology. 2016 Dec 27. cough presentation1

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Living with Environmental Change 2016/2017

I am reaching the end of the semester teaching the module ‘Living with Environmental Change’ together with Professor Lora Fleming. (I have written four blog posts I, II, III and IV last year about the first time we ran this module.) Back then, we had to develop the module from scratch and teach it both on the Penryn campus and the St. Lukes campus in Exeter (a hundred miles east), which made it a lot more work. The experience has been a great deal more relaxed this time around. We have managed to ensnare some excellent guest speakers, ones that have taught before, such as the ECEHHs Dr. Rebecca Lovell who works on the health benefits of the natural environment, and new ones, such as Dr. Anna Harper who works on climate models. Their talks illustrate the breadth of the module: from vibrating diatomic molecules (wiggling CO2 molecules releasing energy causing the greenhouse effect) to Green Gym (taking action to improve the environment while exercising). A great feature of the module is the fact that each student gives a short Pecha Kucha style presentation on their essay topic. This greatly broadens the range of topics that students can learn about, from Aquaculture to Zika, e-Waste, Petridish burgers, heat waves, noise pollution to Blue Carbon (and 35 other topics). We also repeated the excellent tour of the local Wheal Jane mine waste remediation facilities. wgii_ar5_figspm-2I gave a lecture about human pathogens and climate change. I asked each student to do some quick research online and fill out a fact sheet on an assigned pathogen species. Asking the students what facts they found was a nice way to make the lecture a bit more interactive. I asked them not only about the symptoms and treatment of disease, but also whether climate change is expected to impact the occurence of disease. In a lot of cases, the answer is yes. There are many examples of vectorborne diseases moving northwards, eg the Asian tiger mosquito Aedes albopictus is settling in southern Europe with increasing forays into northern Europe. Small outbreaks of Dengue-, Chickungunya- and West Nile fever are already taking place.

Figure 1

Country colouring is based on evidence-based consensus, with green representing a complete consensus on absence of B. pseudomallei and red a complete consensus on presence of B. pseudomallei. Black dots represent geo-located records of melioidosis cases or presence of B. pseudomallei.

Increased water temperatures and reduced salinity (due to increased rainfall and runoff) are strongly correlated with Vibrio infections. Species such as V. parahaemolyticus and V. vulnificus can cause very nasty and sometimes deadly infections and are on the rise in the Baltic (see here). The Fal Estuary around the corner is probably a good habitat too. Burkholderia pseudomallei is another particularly dangerous opportunistic bacterial pathogen that causes a wide range of infections (opportunistic sounds like an understatement; this bug happily infects plants and humans alike). Mainly known to be problematic in South-East Asia and Northern Australia, and also called the ‘Vietnam-time bomb’ for its long incubation time, it can cause very high mortality rates (20-50% even with treatment). Not only does this bug like it warm and moist, it also likes fertilized and saline soils, so warmer weather, sea level rise and  increased agriculture are very likely to benefit this pathogen. This interesting modelling study shows that melidiosis is likely to be greatly underreported, and even endemic in dozens of countries where it has never been reported before. There were many other fascinating examples, including anthrax (Bacillus anthracis) rearing its head in Siberia after the thawing of permafrost and cases of legionaires disease (Legionella pneumophila) associated with increased rainfall. I promise to write a longer blog post next year.

Michiel

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Paper out: No effect of natural transformation on the evolution of resistance to bacteriophages in the Acinetobacter baylyi model system

A long time coming, but the results obtained in NERC-funded research on evolutionary benefits (or lack thereof) of bacterial transformation have now been published. The work was carried out mainly by research tech Amy McLeman, who has since started her PhD in another group here on the Cornwall campus. On board were local collaborators Pawel Sierocinski, Elze Hesse and Angus Buckling, as well as overseas collaborators Nils Huelter, Gabriel Perron and Pal Jarle Johnsen (see this old post about the latter two). A true team effort! I have lazily pasted the abstract and link to the Open Access paper below:

The adaptive benefits of natural transformation, the active uptake of free DNA molecules from the environment followed by incorporation of this DNA into the genome, may be the improved response to selection resulting from increased genetic variation. Drawing analogies with sexual reproduction, transformation may be particularly beneficial when selection rapidly fluctuates during coevolution with virulent parasites (‘the Red Queen Hypothesis’). Here we test this hypothesis by experimentally evolving the naturally transformable and recombinogenic species Acinetobacter baylyi with a cocktail of lytic phages. No increased levels of resistance to phage were found in the wild type compared to a recombination deficient ΔdprA strain after five days of evolution. When exposed to A. baylyi DNA and phage, naturally transformable cells show greater levels of phage resistance. However, increased resistance arose regardless of whether they were exposed to DNA from phage-sensitive or –resistant A. baylyi, suggesting resistance was not the result of transformation, but was related to other benefits of competence. Subsequent evolution in the absence of phages did not show that recombination could alleviate the cost of resistance. Within this study system we found no support for transformation-mediated recombination being an advantage to bacteria exposed to parasitic phages.

McLeman A, Sierocinski P, Hesse E, Buckling A, Perron G, Hülter N, et al. No effect of natural transformation on the evolution of resistance to bacteriophages in the Acinetobacter baylyi model system. Scientific Reports. 2016;6:37144.

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PhD opportunity: the role of natural antimicrobials in selection for antibiotic resistance

img_5998The NERC GW4 Universities Doctoral Training Program is currently advertising PhD projects. This is a slightly complicated process, but basically comes down to prospective students picking a project offered by scientists working at participating universities and institutions and applying to the program. I (Dr Michiel Vos, m.vos@exeter.ac.uk) offer one of these projects as part of a team of  GW4 colleagues (Prof Will Gaze, University of Exeter, Prof Ed Feil, University of Bath and Dr Ruth Airs, Plymouth Marine Laboratory). Below the project description:

The increasing prevalence of antimicrobial resistance (AMR) in bacteria is one of the most pressing problems in global health care. Selection for antibiotic resistance occurs through antibiotic use in the clinic and community and contamination of the environment with heavy metals, biocides and antibiotic residues. However, AMR mechanisms are ancient and their presence in environments with no or minimal exposure to human activity indicates that not all AMR selection is anthropogenic. It is here proposed to test for the first time whether naturally produced antimicrobials can select for resistance to clinical antibiotics. Virtually all organisms, from bacteria to humans, produce antimicrobial compounds. Selection for resistance to these antimicrobials has the potential to also result in resistance to clinical antibiotics when the same bacterial pathways are targeted. Although the ubiquity of interactions between bacteria and antimicrobial producers offers great potential for the molecular diversification of AMR mechanisms, the extent of cross-resistance between naturally produced antimicrobials and clinical antibiotics has remained virtually unstudied.

Seaweeds form a diverse and abundant component of coastal ecosystems and commonly exhibit antimicrobial activity. Seaweed species are colonized by distinct bacterial assemblages, and this process is at least in part mediated by a high diversity of exuded secondary metabolites. Recent research in my lab (Colclough etal in prep) has demonstrated that Staphylococcus aureus strains that were more resistant to clinical antibiotics were on average also more resistant to seaweed extracts. The fact that seaweeds can select for bacteria that are resistant to their metabolites and the observation of cross-resistance between seaweed antimicrobials and clinical antibiotics suggests that there is potential for seaweeds to select for AMR. This PhD project will 1) test whether distinct seaweeds harbour distinct antibiotic resistance genes using metagenomic sequencing, 2) test whether reservoirs of resistance genes can be transferred from seaweed-associated bacterial metagenomes to opportunistic pathogens using functional metagenomics and 3) identify human pathogens on seaweeds and test whether they are more resistant to antibiotics than conspecifics from other environmental reservoirs using whole genome sequencing.

It is critical to understand natural processes governing selection for AMR in the environment. It has been estimated that there are over six million exposure events to cephalosporin-resistant E. coli through recreational use of coastal bathing water in England and Wales alone, demonstrating the potential risks of environmental reservoirs of AMR to human health. This project will allow a first insight into the potential of species interactions to select for AMR mechanisms that confer cross-resistance to clinically relevant antibiotics.

To be clear: the project below is funded only when YOU decide to select this particular (and excellent) project AND are offered entry to the PhD program. See the DTP site for eligibility details etc and the University of Exeter postgraduate research page to apply. The deadline for application is January 6th 2017.

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