Paper Out: Kin discrimination promotes horizontal gene transfer between unrelated strains in Bacillus subtilis

Although this blog has entered a period of dormancy (and I have moved to twitter), I willkeep adding brief posts about new papers. This was a study led by Polonca Stefanic and Ines Mandic-Mulec at the University of Ljubljana that was great to have been involved in. From the Abstract:

Bacillus subtilis is a soil bacterium that is competent for natural transformation. Genetically distinct B. subtilis swarms form a boundary upon encounter, resulting in killing of one of the strains. This process is mediated by a fast-evolving kin discrimination (KD) system consisting of cellular attack and defence mechanisms. Here, we show that these swarm antagonisms promote transformation-mediated horizontal gene transfer between strains of low relatedness. Gene transfer between interacting non-kin strains is largely unidirectional, from killed cells of the donor strain to surviving cells of the recipient strain. It is associated with activation of a stress response mediated by sigma factor SigW in the donor cells, and induction of competence in the recipient strain. More closely related strains, which in theory would experience more efficient recombination due to increased sequence homology, do not upregulate transformation upon encounter. This result indicates that social interactions can override mechanistic barriers to horizontal gene transfer. We hypothesize that KD-mediated competence in response to the encounter of distinct neighbouring strains could maximize the probability of efficient incorporation of novel alleles and genes that have proved to function in a genomically and ecologically similar context.

Stefanic, P., Belcijan, K., Kraigher, B., Nesme, J., Madsen, J.S., Kovac, J., Sørensen, S.J., Vos, M. and Mandic-Mulec, I., 2021. Kin discrimination promotes horizontal gene transfer between unrelated strains in Bacillus subtilis. Nature Communications, 12(1), pp.1-11.

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Twitter

Breaking (ahem): I have f i n a l l y joined twitter. Although some of my misgivings about this medium were rapidly confirmed, I hope it will be a useful tool to keep abreast of new findings and also alert colleagues of what comes out of our lab. Find me on: @Michiel_Vos_010. Although I feel blogging is not the optimal way to engage (I simply do not have enough time to write ‘proper’ blog posts), I will keep posting about PhD opportunities and new papers here (and post pics of Cornish underwater life on my other blog).

Also, I just did a little fun ‘Microbe of the Month’ feature in Trends in Microbiology on my favourite bacterium Myxococcus xanthus, see here. A fascinating bug!




The life cycle of M. xanthus. Cells swarm in social groups using S-motility, with individual cells exploring the surrounding environment using A-motility. Even genetically closely related swarms do not merge upon encounter. Swarms collectively lyse prey cells. Predation stimulates cell reversals regulated by a specialized chemosensory system, the Frz pathway, that are manifested as swarm rippling. Starvation induces a cascade of developmental signals (A, B, C, D and E signal) that leads to fruiting body formation and sporulation. Fruiting bodies could potentially disperse via passive or active transport, although this has not been observed. The life cycle can start anew when peripheral rods sense nutrients, triggering the germination of spores and leading to the formation of a new swarm.
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Paper Out: Does Diversity Beget Diversity in Microbiomes?

A collaboration I was lucky to be involved in led by Jesse Shapiro and PhD student Naima Madi (University of Montreal, although Jesse has now moved across the road to McGill) and with Carmen Lia Murall and Pierre Legendre has now been published. In this study, we used a vast dataset of 16S sequences from the Earth Microbiome Project (around 10 million of em!) to test whether microbiome diversification (via de novo evolution or via immigration) was positively or negatively influenced by standing microbiome diversity. As usual I am going to be lazy and leave it at that and just paste the Abstract below.

Microbes are embedded in complex communities where they engage in a wide array of intra- and inter-specific interactions. The extent to which these interactions drive or impede microbiome diversity is not well understood. Historically, two contrasting hypotheses have been suggested to explain how species interactions could influence diversity. ‘Ecological Controls’ (EC) predicts a negative relationship, where the evolution or migration of novel types is constrained as niches become filled. In contrast, ‘Diversity Begets Diversity’ (DBD) predicts a positive relationship, with existing diversity promoting the accumulation of further diversity via niche construction and other interactions. Using high-throughput amplicon sequencing data from the Earth Microbiome Project, we provide evidence that DBD is strongest in low-diversity biomes, but weaker in more diverse biomes, consistent with biotic interactions initially favouring the accumulation of diversity (as predicted by DBD). However, as niches become increasingly filled, diversity hits a plateau (as predicted by EC).

Madi, Naïma Jesse, Michiel Vos, Carmen Lia Murall, Pierre Legendre, and B. Jesse Shapiro (2020). “Does diversity beget diversity in microbiomes?.”eLife 2020;9:e58999 doi: 10.7554/eLife.58999.

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Paper Out: The evolution of bacterial pathogens in the Anthropocene

A review paper I wrote just came out in Infection Genetics and Evolution. Inspired by my undergraduate teaching on environment and human health, and an interesting FEMS symposium last year, I chose to explore the relationship between environmental degradation and bacterial evolution. This has been done by others already (most notably by Michael Gillings), but a recent increase in papers on the topic warranted another look. The paper is not open access so feel free to send me an email for a reprint (m.vos@exeter.ac.uk). From the Abstract:

Humankind has become a primary driver of global environmental and climate change. The extent of planetary change is such that it has been proposed to classify the current geological age as the ‘Anthropocene’. Anthropogenic environmental degradation presents numerous threats to human health and wellbeing, including an increased risk of infectious disease. This review focuses on how processes such as pollution, climate change and human-mediated dispersal could affect the evolution of bacterial pathogens. Effects of environmental change on the ‘big five’ of evolution: mutation rate, recombination (horizontal gene transfer), migration, selection and drift are discussed. Microplastic pollution is used as a case study to highlight the combined effects of some of these processes on the evolutionary diversification of human pathogens. Although the evidence is still incomplete, a picture is emerging that environmental pathogens could evolve at increased rates in the Anthropocene, with potential consequences for human infection.

Planetary history and near future represented on a log-scale axis. The log-scale allows plotting of events in deep geological time, pre-historical time, historical time, the present and the future. Selected key events in evolutionary- and human history are indicated. The Industrial Revolution is here taken as the starting point of the Anthropocene. RCP 8.5 = Representative Concentration Pathway delivering global warming at an average of 8.5 watts per square meter across the planet, resulting in a temperature increase of about 4.3 °C by 2100 relative to pre-industrial time. The logscale representation of planetary history was inspired by jeff smith (http://matryoshka.org/).

Vos, M., 2020. The evolution of bacterial pathogens in the Anthropocene. Infection, Genetics and Evolution, p.104611.

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PhD Opportunity

The South West Biosciences Doctoral Training Partnership 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: Dr Mahasweta Saha and Dr. Ruth Airs at the Plymouth Marine Laboratory and Dr. Chris Lowe at the University of Exeter and in collaboration with the Cornish Seaweed Company. Below the project description:

Background and objectives: Seaweeds underpin some of the most extensive and productive coastal ecosystems globally,responsible for a suite of ecological functions such as the provision of habitats and carbon sequestration. Seaweeds are also superfoods, being a rich source of minerals, vitamins, protein and fibre, and have a commercial impact as seaweed farming is rapidly expanding globally, including in Europe. However, similar to land plants, seaweeds are susceptible to infectious diseases, resulting in major losses to multi-billion-dollar crops as well as having potential ecosystem impacts on natural populations.

Seaweeds are influenced by complex interactions with microbial communities and seaweeds can use an array of infochemicals to communicate with bacteria on their surface and in their surroundings. Seaweeds use this ‘cross-talk’ to defend against pathogens (foes) and attract beneficial bacteria (friends) (Figure 1) ensuring their health and fitness. This chemical ‘language’ can be altered by changing abiotic factors influencing the health and fitness of the seaweed. Using two economically important edible seaweeds, the objective of this PhD project is to understand the ecological drivers of seaweed diseases under different relevant abiotic stressors and find solutions to mitigate or prevent disease. You will test different abiotic regimes to minimize infection of model seaweeds, identify the pro- and anti-microbials, map metabolic information (via metabolomics in collaboration with Prof. S. Prado, Natural History Museum, Paris) and use high throughput sequencing to characterize microbiota of healthy and diseased individuals.

Figure 1: Conceptual diagram illustrating the role of pro-microbials  and anti-microbials in attraction of beneficial epibacteria and deterrence of detrimental bacteria like pathogens. Figure adapted from Schmidt and Saha 2020, New Phytologist.

Training: You will use an interdisciplinary approach combining chemical ecology, microbiology, molecular biology and analytical chemistry. During your PhD, you will develop advanced lab and field research skills plus transferable skills (e.g. infection bioassays, high-throughput sequencing and mass spectrometry) to support a future career in academia or the biotech and agritech industry. You will be also trained in multivariate statistics (in collaboration with Dr P. Somerfield, PML) and cost-benefit analysis (in collaboration with Dr S. Satyendranath, PML) and receive hands on training while working with a seaweed farm (in collaboration with Mr. Tim van Berkel, Cornish Seaweed Company). You will be fully supported to present your work at international conferences, publish high quality research papers and to build your national and international network of collaborations. PML offers a unique environment for PhD students, having the facilities and collaborative groups which are of critical importance for the success of this multidisciplinary project. Here, you would benefit from the nurturing research culture that PML offers in all areas of marine ecology, microbiology, molecular biology, and climate change research.

Person specification: We seek a curious, highly motivated, and self-reliant student, ideally with a biochemical background and interests in commercial exploitation and food security issues.

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Paper Out: Determining the prevalence, identity and possible origin of bacterial pathogens in soil

I am pleased to have an Open Access paper out in Environmental Microbiology with visiting MSc student Jacopo Ferraresso, MbyREs student Benedict Lawson (shared first authors), Sion Bayliss and Sam Sheppard from the University of Bath, Barbara Cardazzo from the University of Padua and Angus Buckling and Will Gaze from the University of Exeter: “Determining the prevalence, identity and possible origin of bacterial pathogens in soil“.

It follows up from a first study (see this post) developing the virulence model system Galleria mellonella to selectively isolate potential human pathogens from the environment, in this case soil environments. From the Abstract:

Soil biomes are vast, exceptionally diverse and crucial to the health of ecosystems and societies. Soils also contain an appreciable, but understudied, diversity of opportunistic human pathogens. With climate change and other forms of environmental degradation potentially increasing exposure risks to soilborne pathogens, it is necessary to gain a better understanding of their ecological drivers. Here we use the Galleria mellonella insect virulence model to selectively isolate pathogenic bacteria from soils in Cornwall (UK). We find a high prevalence of pathogenic soil bacteria with two genera, Providencia and Serratia, being especially common. Providencia alcalifaciens, P. rustigianii, Serratia liquefaciens and S. plymuthica strains were studied in more detail using phenotypic virulence and antibiotic resistance assays and whole‐genome sequencing. Both genera displayed low levels of antibiotic resistance and antibiotic resistance gene carriage. However, Serratia isolates were found to carry the recently characterized metallo‐β‐lactamase blaSPR‐1 that, although not conferring high levels of resistance in these strains, poses a potential risk of horizontal transfer to other pathogens where it could be fully functional. The Galleria assay can be a useful approach to uncover the distribution and identity of pathogenic bacteria in the environment, as well as uncover resistance genes with an environmental origin.

Michiel Vos

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Magic Seaweed

Long time no post in these strange times. Lots of upheaval with closed labs and online teaching preparations, which has meant more work to do in less time (half my time was spent homeschooling). This post has nothing to do with ongoing research, but it is about biology and Cornwall. (Specifically, it is about marine biology, and marine sciences are a strong focus of the University of Exeter.) This is a photo I made in spring snorkeling here in Falmouth that won the joint top prize in the annual Hilda Canter-Lund Photo competition organised by the British Phycological Society. This award was established in recognition of Hilda Canter-Lund, whose photomicrographs of freshwater algae combined high technical and aesthetic qualities whilst still capturing the quintessence of the organisms she was studying. The caption:

Carpodesmia tamariscifolia (Bushy Rainbow Wrack) framed by Himanthalia elongata (Thong  Weed) in a rockpool in Falmouth, Cornwall, U.K.

I took this photo of this stunningly beautiful iridescent Rainbow Wrack ( spring 2020 at a low tide when this rockpool was no more than a meter deep. This species is a perennial that forms a home to many animals, from sponges to tunicates, and is often used by the Bull Huss to attach its egg cases to. Many seaweed species also grow epiphytically on Bushy Rainbow Wrack, such as the invasive red species Bonnemaisonia hamifera on this photo. Photo taken using an Olympus OM-D E-M5 Mark II with an 8mm fisheye lens and with a single automatic strobe.

For more underwaterphotos see my nerd blog ‘An Bollenessor‘ (which means ‘The Rockpoolhunter’ in the Cornish language).

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Paper out: Zinc can counteract selection for ciprofloxacin resistance

Pleased to have a paper (open Access) out with collaborators Uli Klumper, Elze Hesse and Will Gaze and former MSc students Louise Sibleyras and Lai Ka Lo (see Lai Ka in this old post). I cannot really say it better than the Abstract (and I am lazy), so I’ll leave it at that!

Antimicrobial resistance (AMR) has emerged as one of the most pressing threats to public health. AMR evolution occurs in the clinic but also in the environment, where antibiotics and heavy metals can select and co-select for AMR. While the selective potential of both antibiotics and metals is increasingly well-characterized, experimental studies exploring their combined effects on AMR evolution are rare. It has previously been demonstrated that fluoroquinolone antibiotics such as ciprofloxacin can chelate metal ions. To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and a ciprofloxacin-resistant Escherichia coli strain across a gradient of ciprofloxacin concentrations in presence and absence of zinc. The presence of zinc reduced growth of both strains, while ciprofloxacin inhibited exclusively the susceptible one. When present in combination zinc retained its inhibitory effect, while ciprofloxacin inhibition of the susceptible strain was reduced. Consequently, the minimal selective concentration for ciprofloxacin resistance increased up to five-fold in the presence of zinc. Environmental pollution usually comprises complex mixtures of antimicrobial agents. In addition to the usual focus on additive or synergistic interactions in complex selective mixtures, our findings highlight the importance of antagonistic selective interactions when considering resistance evolution.

Michiel Vos, Louise Sibleyras, Lai Ka Lo, Elze Hesse, William Gaze, Uli Klümper, Zinc can counteract selection for ciprofloxacin resistance, FEMS Microbiology Letters, , fnaa038, https://doi.org/10.1093/femsle/fnaa038

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Global Climate Strike

I will take part today in the Global Climate Strike, specifically, the event held here on the University of Exeter’s Penryn Campus. I teach two undergraduate modules ‘Living with Environmental Change’ and ‘Oceans and Human Health’. Both modules focus on the many ways humans degrade the natural environment, through pollution and climate change, and how in turn this affects human health, directly and indirectly. I have learned a lot teaching these modules, and the scale of the problems we face is truly frightening. The most frustrating part is that we have the solutions to turn the tide already, for instance, large-scale nature restoration will result in carbon capture, prevent against effects of extreme weather and preserve biodiversity. It is a matter of political and societal will that is the real problem. I hope this strike helps in raising awareness and precipitating radical change.

Michiel

P.S. I highly recommend the site ‘Our World in Data‘ from which the above graph was taken.

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Paper Out: Heavy metal pollution and co-selection for antibiotic resistance: A microbial palaeontology approach

A paper that was a long time in the making came out last week. Lead author Andy Dickinson (since moved for a PhD in astrobiology in Edinburgh) did a Masters by Research project with Britt Koskella (since moved to Berkeley) and myself. From the Abstract:

Frequent and persistent heavy metal pollution has profound effects on the composition and activity of microbial communities. Heavy metals select for metal resistance but can also co-select for resistance to antibiotics, which is a global health concern. We here document metal concentration, metal resistance and antibiotic resistance along a sediment archive from a pond in the North West of the United Kingdom covering over a century of anthropogenic pollution. We specifically focus on zinc, as it is a ubiquitous and toxic metal contaminant known to co-select for antibiotic resistance, to assess the impact of temporal variation in heavy metal pollution on microbial community diversity and to quantify the selection effects of differential heavy metal exposure on antibiotic resistance. Zinc concentration and bioavailability was found to vary over the core, likely reflecting increased industrialisation around the middle of the 20th century. Zinc concentration had a significant effect on bacterial community composition, as revealed by a positive correlation between the level of zinc tolerance in culturable bacteria and zinc concentration. The proportion of zinc resistant isolates was also positively correlated with resistance to three clinically relevant antibiotics (oxacillin, cefotaxime and trimethoprim). The abundance of the class 1 integron-integrase gene, intI1, marker for anthropogenic pollutants correlated with the prevalence of zinc- and cefotaxime resistance but not with oxacillin and trimethoprim resistance. Our microbial palaeontology approach reveals that metal-contaminated sediments from depths that pre-date the use of antibiotics were enriched in antibiotic resistant bacteria, demonstrating the pervasive effects of metal-antibiotic co-selection in the environment.

Check out the Open Access paper on the Envrionment International website:

Dickinson, A.W., Power, A., Hansen, M.G., Brandt, K.K., Piliposian, G., Appleby, P., O’Neill, P.A., Jones, R.T., Sierocinski, P., Koskella, B. and Vos, M., 2019. Heavy metal pollution and co-selection for antibiotic resistance: a microbial palaeontology approach. Environment international, 132, p.105117.

P.S.

This was a project in collaboration with Exeter Geographer Dr. Richard Jones who sadly passed away before publication. He was one of the most enthusiastic and collegial researchers I have ever met and is sorely missed by all.

P.S.P.S.

The work followed on from even older student projects supervised by Britt and myself where we are interested in isolating bacteria and their viruses from sediment cores to track their co-evolution through time. In the end, that proved impossible, although that project  taught us a lot about the coring approach and greatly helped designing Andy’s project. See this post and this post describing these previous coring adventures.

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