New papers and arrivals: September 2018
We are welcoming Reena Debray, our newest graduate student, to the lab! Reena’s time in the lab is off to a great start as she seeks to quantify the impact of phages on plant resistance to pathogens. Stay tuned for some great science.
I am also happy to share two new papers from the lab:
1. Berg, M., & Koskella, B. (2018). Nutrient-and Dose-Dependent Microbiome-Mediated Protection against a Plant Pathogen. Current Biology, 28(15), 2487-2492.
During her final year of graduate school, Maureen Berg spent time in our lab to learn about plant microbiomes (to complement her amazing work on gut microbiota of C. elegans, as can be seen here: https://www.nature.com/articles/ismej2015253). Maureen and I set out to ask a very simple question: does the tomato phyllosphere protect against pathogen colonization. We used a new method we’ve been developing in the lab, where we transplant the microbiomes from field-grown tomato plants onto mostly sterile plants in the growth chamber. In this way, we can control host genotype, and other extrinsic factors, and examine how plants with these augmented microbiomes differ in phenotype from those without. Of course we had to add a twist, and in this case we thought we would ask how dose impacts microbiome-mediated protection. To make a long story short, the answer is that it does! But not always in the way we would have predicted – sometimes less was better. We then tested these patterns more explicitly using a constructed community of 12 culturable isolates from the tomato phyllosphere, and were able to confirm this counterintuitive result – which we are now following up on. Moreover, we accidentally discovered that fertilizing the plants before the experiment abolished the previously observed protection – a result we confirmed with a fully factorial experiment. When the plants were not fertilized, pathogen colonization depended critically on whether the phyllosphere had been colonized by commensal bacteria, but when they were fertilized, the phyllosphere no longer had any observable protective effects. See news coverage of the work here: http://news.berkeley.edu/2018/07/26/fertilizer-destroys-plant-microbiomes-ability-to-protect-against-disease/
2. Koskella, B., & Taylor, T. B. (2018). Multifaceted Impacts of Bacteriophages in the Plant Microbiome. Annual review of phytopathology, 56, 361-380.
In collaboration with Tiffany Taylor at Bath University, we spent some time thinking about the myriad ways in which phages might impact the plant microbiome. This blossoming field nicely complements work from the human microbiome (and other systems) suggesting that phages are key components of the microbiome, shaping composition, diversity, and function. This means there is plenty of work to be done in order to determine how and when such knowledge can be leveraged in human health and agriculture.
More papers, awards, and grants: July 2018
Congratulations to graduate student Norma Morella, who received the College of Natural Resources M.J. Vlamis Award for high level of academic distinction!
It’s no surprise given the great new results she has published:
(1) Morella, N. M., Gomez, A. L., Wang, G., Leung, M. S., & Koskella, B. (2018). The impact of bacteriophages on phyllosphere bacterial abundance and composition. Molecular ecology, 27(8), 2025-2038.
We show that naturally occurring phage communities in the tomato phyllosphere have important impacts on both the abundance (short term) and diversity (longer term) of colonizing bacteria during phyllosphere microbiome establishment. Taking an experimental approach, we were able to ‘deplete’ phages from field collected microbiomes using filtration (see below) and then compare the initial establishment of microbial communities on leaves in the presence versus absence of these lytic phages. Our results suggest the presence of phages decreases abundance of total bacteria 24 hours after colonization on new plants, but increases bacterial diversity when measured a week later.
(2) Morella, N. M., Yang, S. C., Hernandez, C. A., & Koskella, B. (2018). Rapid Quantification of Bacteriophages and Their Bacterial Hosts in Vitro and in Vivo using Droplet Digital PCR. Journal of virological methods.
We have spent the last few years developing a new method to quantify bacterial and phage abundance and dynamics both in vitro and in vivo. Using droplet digital PCR, we are working to get more accurate measures of bacteria/phage densities in order to more precisely address questions of bacterial and phage fitness, phage-phage competition, and the impact of phages on their bacterial host populations. We are very happy with the method, especially as it is saving us a great deal of time and plastic that we used to spend on CFU (colony forming units) and PFU (plaque forming units) dilution plating.
Finally, we are also celebrating the receipt of an NSF grant from DEB to study the importance of microbiome transmission in shaping the evolution and ecology of (plant) host-microbiomes interactions. Stay tuned for a postdoctoral opportunity announcement.
P.s. we also discovered that Carrot Dogs are amazing!!! https://www.brandnewvegan.com/recipes/smoky-vegan-carrot-dogs
Papers and awards: April 2018
It’s been a busy year so far! Among the recent exciting news:
(1) Fourth year graduate student Norma Morella, AmGen summer scholar Annika Gomez (now heading to MIT for her NSF-funded Phd), undergraduate researchers Grant Wang, Michelle Leung, and I have just published a paper in Molecular Ecology showing the impact that a naturally occurring phage community can have on microbiome colonization of new host plants. In short: phages reduce bacterial density overall and seem to shape both the alpha and beta diversity of the phyllosphere during initial establishment.
(2) Third year graduate student Cathy Hernandez was accepted into the 2018 Australia-Americas PhD Research Internship Program to spend the upcoming summer working with Jeremy Barr at Monash University. More to come soon on this exciting project!
(3) First year graduate student Elijah Mehlferber has been awarded honorable mention for his NSF GRFP proposal this year. He is seeking to better understand how competition within the phyllosphere can alter plant susceptibility to pathogens.
(4) Incoming graduate student, and former summer AmGen Scholar, Reena Debray has been awarded a NSF GRFP for her planned work to examine the role phages play in shaping bacterial adaptation to host plants. Welcome back to the lab Reena!
(5) Undergraduate researcher Callie Cuff, who is completing her honors thesis in the lab examining host range of naturally occurring phages from pear trees, has been awarded the Nutritional Sciences Department Citation Award in recognition of her distinguished undergraduate work.
(6) Undergraduate researcher Shirley Zhang has been awarded a 2018 ASPB Summer Undergraduate Research (SURF) Fellowship to continue her amazing work on seed-associated microbiota and disease.
(7) Undergraduate researcher Kore Lum has been awarded a URAP Summer Award to support her research on phage-mediated selection of the plant pathogen P. syringae.
Congratulations to all!
A few new papers from the lab: February 2018
(1) The microbiome beyond the horizon of ecological and evolutionary theory published in Nature Ecology and Evolution. Britt’s coauthors, Jess Metcalf from Princeton and Lindsay Hall from the Quadrum Institute set out to ask where current evolutionary and ecological theory might fall short when being applied to microbiome research. It was a very challenging and fun piece to write! (found here: https://www.nature.com/articles/s41559-017-0340-2).
(2) Phd Student, Norma Morella, and Britt took a stab at figuring out what we might learn about the interaction between the immune system and the microbiome by looking across systems. This short opinion piece certainly got us thinking, and emphasized that there is still a lot of work to be done (The Value of a Comparative Approach to Understand the Complex Interplay between Microbiota and Host Immunity can be found here: https://www.frontiersin.org/articles/10.3389/fimmu.2017.01114/full).
(3) In collaboration with Derek Lin and Henry Lin in the Department of Medicine at University of New Mexico, we recently examined the promise of phage therapy and its complex history. (Phage therapy: An alternative to antibiotics in the age of multi-drug resistance can be found here: chttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547374/).
(4) As part of a large theoretical undertaking, Britt was coauthor on a paper examining when and how you can generate frequency dependent selection in host-parasite coevolution without the strict specificity for infection that is typically built into models. This work suggests that fluctuating selection (important in many theories, including the Red Queen Hypothesis for the maintenance of sex) might be far more common than predicted based on infection genetic mechanisms. Paper can be found here: http://rspb.royalsocietypublishing.org/content/284/1866/20171615
Also, if you’re interested, Britt partook in a QandA for Current Biology about everything from her career to the future of science. More here: http://www.cell.com/current-biology/pdf/S0960-9822(17)31395-7.pdf
Britt awarded the ASM Young Investigator Prize September 2017
Britt is one of three recipients of the American Society for Microbiology’s Young Investigator Award, which “Recognizes and rewards early career scientists for research excellence and potential in microbiology and infectious disease.” She will be accepting the award, and giving a research seminar, at ASM Microbe in Atlanta this coming Summer.
Now out in the New Phytologist: exploring the relationship between tree health and the bark microbiome May 2017
Summary: Host susceptibility to pathogens can be shaped by genetic, ecological, and evolutionary factors. The ability to predict the spread of disease therefore requires an integrated understanding of these factors, including effects of pests on pathogen growth and competition between pathogens and commensal microbiota for host resources. We examined interactions between the leaf-mining moth Cameraria ohridella, the bacterial causal agent of bleeding canker disease Pseudomonas syringae pv aesculi, and the bark-associated microbiota of horse chestnut (Aesculus hippocastanum) trees. Through surveys of > 900 trees from 60 sites in the UK, we tested for ecological or life history predictors of leaf miner infestation, bleeding canker, or coinfection. Using culture-independent sequencing, we then compared the bark microbiomes from 46 trees to measure the association between microbiome composition and key ecological variables, including the severity of disease. Both pest and pathogen were found to respond to tree characteristics, but neither explained damage inflicted by the other. However, we found a clear loss of microbial diversity and associated shift in microbiome composition of trees as a function of disease. These results show a link between bark-associated microbiota and tree health that introduces the intriguing possibility that tree microbiota play key roles in the spread of disease.
New paper by Sean Meaden in Environmental Microbiology Reports examining the microbiota of English Oak in Wytham Woods May 2016
Summary: Drivers of bacterial community assemblages associated with plants are diverse and include biotic factors, such as competitors and host traits, and abiotic factors, including environmental conditions and dispersal mechanisms. We examine the roles of spatial distribution and host size, as an approximation for age, in shaping the microbiome associated with Quercus robur woody tissue using culture-independent 16S rRNA gene amplicon sequencing. In addition to providing a baseline survey of the Q. robur microbiome, we screened for the pathogen of acute oak decline. Our results suggest that age is a predictor of bacterial community composition, demonstrating a surprising negative correlation between tree age and alpha diversity. We find no signature of dispersal limitation within the Wytham Woods plot sampled. Together, these results provide evidence for niche-based hypotheses of community assembly and the importance of tree age in bacterial community structure, as well as highlighting that caution must be applied when diagnosing dysbiosis in a long-lived plant host. Read more here!
Congratulations to Cathy Hernandez on her NSF graduate research fellowship!
Cathy’s first year in the lab is off to a great start, with plants in the greenhouse ready for her first multigenerational bacteria – phage selection experiment. The funding from her GRFP will be used to take her research out into the field. Watch this space, and well done Cathy!
Congratulations to DR Sean Meaden! What a great few years it’s been, and best of luck with all of your future sciencing. We will miss you!!
Last week I traveled back across the sea and down the coast to the beautiful (but very rainy) Cornwall to celebrate the successful PhD viva (aka defense) of my first PhD student, Sean Meaden. A big thanks to external examiner Prof Martha Clokie for insightful comments and for hanging around to celebrate (despite my bailing early due to severe jet lag – and I can’t even blame the baby). The visit was bittersweet, as the joy of celebrating Sean’s success was coupled with the sadness of no longer having Sean in the lab. Sean impressed me every single day that he was part of the lab; whether it was learning how to develop bioinformatic pipelines to analyze microbiome datasets, sequencing and annotating phage genomes, running experiments in the greenhouse, or volunteering in Sierra Leone during the ebola outbreak, Sean’s work ethic, integrity, and love of science made him an absolute pleasure to work with. Oh yeah, and he happens to be one of the nicest, sincere, and well-balanced people I know. I have no doubt that Sean’s future scientific endeavors will be hugely successful and I look forward to following his continued growth as a scientist, as well as to our continued collaborations. Congratulations Sean!
P.s. Thanks to Sarah Paul for baking and designing the amazing phage and tomato cakes!
New paper in AREES exploring microbial adaptation in nature (collaboration with Dr. Michiel Vos at the University of Exeter, ESI) Dec 2015
Abstract: 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.
You can access the paper here!
Britt and Nicole have a new paper out exploring the generality of bacterial resistance to phage across time and space July 2015
Koskella, B., and N. Parr. 2015. The evolution of bacterial resistance against bacteriophages in the horse chestnut phyllosphere is general across both space and time. Philosophical Transactions of the Royal Society of London B: Biological Sciences 370. HERE
Abstract: Insight to the spatial and temporal scales of coevolution is key to predicting the outcome of host–parasite interactions and spread of disease. For bacteria infecting long-lived hosts, selection to overcome host defences is just one factor shaping the course of evolution; populations will also be competing with other microbial species and will themselves be facing infection by bacteriophage viruses. Here, we examine the temporal and spatial patterns of bacterial adaptation against natural phage populations from within leaves of horse chestnut trees. Using a time-shift experiment with both sympatric and allopatric phages from either contemporary or earlier points in the season, we demonstrate that bacterial resistance is higher against phages from the past, regardless of spatial sympatry or how much earlier in the season phages were collected. Similarly, we show that future bacterial hosts are more resistant to both sympatric and allopatric phages than contemporary bacterial hosts. Together, our results suggest the evolution of relatively general bacterial resistance against phages in nature and are contrasting to previously observed patterns of phage adaptation to bacteria from the same tree hosts over the same time frame, indicating a potential asymmetry in coevolutionary dynamics.
New paper by Sean exploring context-dependent nature of costs of resistance to phage now online in Evolution April 2015
Meaden, S., Paszkiewicz, K., & Koskella, B. (2015). The cost of phage resistance in a plant pathogenic bacterium is context‐dependent. Evolution. HERE
Abstract: Parasites are ubiquitous features of living systems and many parasites severely reduce the fecundity or longevity of their hosts. This parasite-imposed selection on host populations should strongly favor the evolution of host resistance, but hosts typically face a trade-off between investment in reproductive fitness and investment in defense against parasites. The magnitude of such a trade-off is likely to be context-dependent, and accordingly costs that are key in shaping evolution in nature may not be easily observable in an artificial environment. We set out to assess the costs of phage resistance for a plant pathogenic bacterium in its natural plant host versus in a nutrient-rich, artificial medium. We demonstrate that mutants of Pseudomonas syringae that have evolved resistance via a single mutational step pay a substantial cost for this resistance when grown on their tomato plant hosts, but do not realize any measurable growth rate costs in nutrient-rich media. This work demonstrates that resistance to phage can significantly alter bacterial growth within plant hosts, and therefore that phage-mediated selection in nature is likely to be an important component of bacterial pathogenicity.
Tomato leaf infected with Pseudomonas syringae pv tomato 48 hours previously. Credit: Alexander Rose.
Paper exploring the transition of the human-associated bacterium, Helicobacter pylori, now online and open access at Evolutionary Applications Nov 2014
Lin, D., & Koskella, B. (2014). Friend and foe: factors influencing the movement of the bacterium Helicobacter pylori along the parasitism‐mutualism continuum. Evolutionary Applications. HERE
Abstract: Understanding the transition of bacterial species from commensal to pathogen, or vice versa, is a key application of evolutionary theory to preventative medicine. This requires working knowledge of the molecular interaction between hosts and bacteria, ecological interactions among microbes, spatial variation in bacterial prevalence or host life history, and evolution in response to these factors. However, there are very few systems for which such broad datasets are available. One exception is the gram-negative bacterium, Helicobacter pylori, which infects upwards of 50% of the global human population. This bacterium is associated with a wide breadth of human gastrointestinal disease, including numerous cancers, inflammatory disorders, and pathogenic infections, but is also known to confer fitness benefits to its host both indirectly, through interactions with other pathogens, and directly. Outstanding questions are therefore why, when, and how this bacterium transitions along the parasitism–mutualism continuum. We examine known virulence factors, genetic predispositions of the host, and environmental contributors that impact progression of clinical disease and help define geographical trends in disease incidence. We also highlight the complexity of the interaction and discuss future therapeutic strategies for disease management and public health in light of the longstanding evolutionary history between the bacterium and its human host.
New book chapter in collaboration with Dr. Tiffany Taylor on the potential impacts of phages on plant-bacterial interactions
Koskella, B. and Taylor, T. B. The potential role of bacteriophages in shaping plant-bacterial interactions, in Plant-Bacterial Interactions, Murillo, J., Jackson, R. W., Arnold, D., and Vinatzer, B. (eds). Horizon Scientific Press, Norwich UK.
The American Naturalist Vice Presidential Symposium issue is now online ahead of print, including Britt’s new work on phage adaptation through time and space, as well as open questions in disease ecology and evolution (July 2014)
Check the papers out here:
(press release here: http://www.amnat.org/an/newpapers/VPKoskella.html)
Our work on phages in Horse chestnut trees highlighted in Current Biology (June 2014)
Check out this great piece on phage therapy for plants and people by Michael Gross in Current Biology:
Nice coverage of the work being done in the lab, especially by Sean Meaden.
New paper in collaboration with Prof Mike Brockhurst now online and open access (March 2014)
“Bacteria-phage coevolution, the reciprocal evolution between bacterial hosts and the phages that infect them, is an important driver of ecological and evolutionary processes in microbial communities. There is growing evidence from both laboratory and natural populations that coevolution can maintain phenotypic and genetic diversity, increase the rate of bacterial and phage evolution and divergence, affect community structure, and shape the evolution of ecologically relevant bacterial traits. Although the study of bacteria phage coevolution is still in its infancy, with open questions remaining about the specificity of the interaction, the gene networks of coevolving partners, and the relative importance of the coevolving interaction in complex communities and environments, there have been some intriguing recent developments. In this review we sum up our current understanding of bacteria-phage coevolution both in the laboratory and in nature, discuss recent findings that demonstrate both the coevolutionary process itself and the impact of coevolution on bacterial phenotype, diversity and interactions with other species, particularly their eukaryotic hosts, and outline future directions for the field.”
Britt is now the research highlights associate editor for Evolutionary Applications (Jan 2014)
First research highlight available now: http://onlinelibrary.wiley.com/doi/10.1111/eva.12146/full
“Evolutionary Applications is the only journal specializing specifically in publishing papers that make contributions to fundamental questions in evolutionary biology using study systems that are of practical or applied importance in topics including, but not limited to: agriculture, aquaculture, biomedicine, biotechnology, climate change, conservation biology, disease biology, forestry, invasion biology, and fisheries and wildlife management. As such, one of our main goals is to promote interest of applied evolution to a diverse audience including evolutionary biologists, ecologists, biomedical researchers, environmental consultants, and biologists within industry, government, and health care. Toward this end, this new series of research highlights will offer brief synopses of new work with direct relevance to readers of Evolutionary Applications from across other journals with the aim of exploring the breadth of potential applications of evolutionary theory from across fields and disciplines.”
If you’ve recently read or written a paper (from any journal) that exemplifies the application of evolutionary theory, please feel free to suggest it for a future highlight!
Sean’s new paper on the risks associated with phage biopesticide use in the environment is out now and open access (Nov 2013)
“Interest in using bacteriophages to control the growth and spread of bacterial pathogens is being revived in the wake of widespread antibiotic resistance. However, little is known about the ecological effects that high concentrations of phages in the environment might have on natural microbial communities. We review the current evidence suggesting phage-mediated environmental perturbation, with a focus on agricultural examples, and describe the potential implications for human health and agriculture. Specifically, we examine the known and potential consequences of phage application in certain agricultural practices, discuss the risks of evolved bacterial resistance to phages, and question whether the future of phage therapy will emulate that of antibiotic treatment in terms of widespread resistance. Finally, we propose some basic precautions that could preclude such phenomena and highlight existing methods for tracking bacterial resistance to phage therapeutic agents.”
My new paper on bacteria-phage coevolution within horse chestnut trees is now out and open access (July 2013)
“It is increasingly apparent that the dynamic microbial communities of long-lived hosts affect their phenotype, including resistance to disease. The host microbiota will change over time due to immigration of new species, interaction with the host immune system, and selection by bacteriophage viruses (phages), but the relative roles of each process are unclear. Previous metagenomic approaches confirm the presence of phages infecting host microbiota, and experimental coevolution of bacteria and phage populations in the laboratory has demonstrated rapid reciprocal change over time. The key challenge is to determine whether phages influence host-associated bacterial communities in nature, in the face of other selection pressures. I use a tree-bacteria-phage system to measure reciprocal changes in phage infectivity and bacterial resistance within microbial communities of tree hosts over one season. An experimental time shift shows that bacterial isolates are most resistant to lytic phages from the prior month and least resistant to those from the future month, providing clear evidence for both phage-mediated selection on bacterial communities and bacterial-mediated selection on phage communities in nature. These reciprocal changes suggest that phages indeed play a key role in shaping the microbiota of their eukaryotic hosts.”
P.s. I have also published the reviews for this paper and my response to these reviews in the “blog” tab here.
New paper on the power of experimental coevolution is now online at TREE (March 2013)
“Coevolution, the process of reciprocal adaptation and counter-adaptation between ecologically interacting species, affects most organisms and is considered a key force structuring biological diversity. Our understanding of the pattern and process of coevolution, particularly of antagonistic species interactions, has been hugely advanced in recent years by an upsurge in experimental studies that directly observe coevolution in the laboratory. These experiments pose new questions by revealing novel facets of the coevolutionary process not captured by current theory, while also providing the first empirical tests of longstanding coevolutionary ideas, including the influential Red Queen hypothesis. In this article, we highlight emerging directions for this field, including experimental coevolution of mutualistic interactions and understanding how pairwise coevolutionary processes scale up within species-rich communities.”
-Brockhurst and Koskella 2013
Our new paper on the importance of understanding phage specificity in natural populations is out! (March 2013)
And it’s open access: http://www.mdpi.com/1999-4915/5/3/806
Why should we care about which bacteria are infected by what phages? Because the underlying specificity for infection is key to predicting if an how phages will effect the bacterial populations and communities in which they are found. We review what is known, what we need to learn, and why it matters. We also present the results from Sean’s masters project, where he tested whether natural phages have narrow or broad host ranges. The answer: both!
Welcome to new masters student, Amy McLeman (March 2013)
Amy will be taking a novel approach to understanding if and how plants might benefit from phages in the environment. Although there is some evidence that viruses move around within plants, it has yet to be determined whether phages can play a role in hindering the establishment of infection by bacterial pathogens.
Watch this space!
Sean Meaden has joined the lab! (Sept 2013)
Sean finished his masters project on characterizing the specificity of natural phages from the horse chestnut phyllosphere and has now begun his doctoral work. For his first project, Sean will be examining the costs associated with bacterial resistance to phages in their natural habitats.
There is good evidence that resisting parasites is costly, but most of this evidence comes from tests in the lab (e.g. our recent paper on resisting multiple phages: here). Sean is taking this a step further to determine what these costs might look like in terms of the bacteria’s ability to infect its plants hosts. Stay tuned for some great results!