postdoc position available: “Context-dependent acquisition of antibiotic resistance mechanisms”

A one-year postdoc position is currently available in my lab at the University of Exeter Cornwall Campus!

The dramatic increase in antimicrobial resistance (AMR) threatens the effective treatment of a wide range of infections and forms a global challenge to public health. To effectively combat AMR, it is crucial we understand the mechanisms by which it evolves. This project will test for the effects of antibiotic concentration and microbiome diversity on mechanisms of AMR evolution. Bacteria can acquire antibiotic resistance via point mutations but are also able to take up resistance genes from other strains and species. The latter process might occur at the same rate as mutation but the relative importance of these two fundamentally distinct genetic mechanisms in generating AMR is not known. The main project aim is to combine antibiotic selection with whole-genome re-sequencing in a bacterial pathogen to identify the prevalence of distinct genetic mechanisms (horizontal gene transfer versus point mutations) responsible for AMR. This project will provide fundamental data on bacterial genome evolution as well as provide a scientific basis for pollution management.

The project is supervised by Dr. Michiel Vos (UEMS), Prof. Will Gaze (UEMS), Prof. Angus Buckling (CLES) and Dr. Ben Temperton (CLES). Work will take place in state-of-the-art microbiology labs at the ESI building at the University of Exeter’s Penryn campus.

Please see here for the job advert. Feel free to contact me for any queries at m.vos@exeter.ac.uk.

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Paper Out: Patterns of cross‐resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials

Although having previously mainly worked in soil- and evolutionary microbiology and currently working in a Medical School, I started out as a marine biologist. After my move to Cornwall my love for the marine environment was rekindled by exploring some of the most beautiful and diverse coastlines in the whole of Europe (see also my nerd blog here). From these snorkel trips, a student project grew: 3d year Medical sciences student Abigail Colclough, now a PhD student at Birmingham) embarked on a project studying antimicrobials produced by seaweeds (see this old post, this paper has been a long time coming!).

I have pasted the Abstract below; the paper is Open Access. We were fortunate to have co-authors Jukka Corander (Helsinki and Oslo), Sam Sheppard and Sion Bayliss (Bath) providing phylogenetic expertise.

Bacteria interact with a multitude of other organisms, many of which produce antimicrobials. Selection for resistance to these antimicrobials has the potential to result in resistance to clinical antibiotics when active compounds target the same bacterial pathways. The possibility of such cross-resistance between natural antimicrobials and antibiotics has to our knowledge received very little attention. The antimicrobial activity of extracts from seaweeds, known to be prolific producers of antimicrobials, is here tested against Staphylococcus aureus isolates with varied clinical antibiotic resistance profiles. An overall effect consistent with cross-resistance is demonstrated, with multi-drug resistant S. aureus strains being on average more resistant to seaweed extracts. This pattern could potentially indicate that evolution of resistance to antimicrobials in the natural environment could lead to resistance against clinical antibiotics. However, patterns of antimicrobial activity of individual seaweed extracts vary considerably and include collateral sensitivity, where increased resistance to a particular antibiotic is associated with decreased resistance to a particular seaweed extract. Our correlation-based methods allow the identification of antimicrobial extracts bearing most promise for downstream active compound identification and pharmacological testing.

Colclough, A., Corander, J., Sheppard, S., Bayliss, S. and Vos, M., Patterns of cross‐resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials. Evolutionary Applications. 2019;1–10. DOI:   10.1111/eva.12762

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Life at the Edge of Sight

Scott Chimileski – microbephotography.com

At the end of last year, I intended a book presentation at the Eden Project. Although a bit late, it is definitely worth a quick blog post, as “Life at the Edge of Sight” is a must-have for anyone interested in microbiology. Between stops in Shanghai and Oxford, authors Scott Chimileski and Roberto Kolter visited Cornwall to give an engaging presentation on the tremendously diverse, ancient and important world of bacteria and other microorganisms. It reminded me of my own plan for a microbiology book (which is distinct from this book) which I blogged about some years ago. I am afraid I would need some type of sabbatical to produce it though and that is not really on the cards. Please check out Scott’s website for more beautiful imagery: scottchimileskiphotography.com.

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Paper Out: Using the wax moth larva Galleria mellonella infection model to detect emerging bacterial pathogens

A good start of the year by having a paper published. I blogged about the bioarxiv* version a while back so will keep it short this time: we injected environmental (water and sediment) samples in the Galleria caterpillar and, where mortality was found to be high, isolated the bacterial pathogens responsible. Four isolates were whole-genome sequenced and two proved to be species never found before in the UK. No other methods would have detected such ‘known unknowns’; perhaps expensive and time-consuming metagenomics would have provided glimpses of the DNA of these species (provided they were at high relative abundance, which they might not have been), but this method would not have given much information on pathogenicity, which was our phenotype of interest. Although conceptually very simple, I am quite excited by the potential of this method. Please have a look, it is Open Access:

Hernandez RJ, Hesse E, Dowling AJ, Coyle NM, Feil EJ, Gaze WH, Vos M. 2019. Using the wax moth larva Galleria mellonella infection model to detect emerging bacterial pathogens. PeerJ 6:e6150 https://doi.org/10.7717/peerj.6150

P.S.

Getting this paper published was a right pain btw: a total of seven rejections over a half-year time period: a personal record! I played with the idea of writing up a detailed dissection of this process but decided against it as it might have come across as a boring moan. Suffice to say it reinforced my belief that there are many things wrong with publishing, including journals that do not accept papers published as preprints (but without explaining why, I am looking at you Emerging Infectious Diseases), journals that demand additional experiments sacrifing animals for no good reason (I am looking at you PLoS Pathogens) or journals rejecting a manuscript even when reviewer comments equate to a (very minor) revision (I am looking at you Emerging Microbes and Infections). OK OK I had a little moan after all.

* The good thing about using Bioarxiv was that during this arduous publication process the manuscript abstract was checked almost 2000 times and it was downloaded as a pdf 360 times.

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Apply to the NERC GW4 PhD studentship “Context-dependent acquisition of antibiotic resistance mechanisms”

Together with collaborators Prof. Will Gaze (College of Medicine and Health, Exeter), Prof. Angus Buckling (Biosciences, Exeter) and Prof. Ed Feil (Milner Centre for Evolution, Bath) I have an advert up for a 3.5 year PhD position here in Penryn. Funding is contingent on having an excellent (and eligible) candidate to apply. For all the technical details see HERE. A short summary is pasted below (with some more details on project aims, methods and training via the link above):

The dramatic increase in antimicrobial resistance (AMR) forms a global challenge to public health. It is increasingly understood that the natural environment plays a key role in AMR evolution. Pharmaceutical residues and other pollutants in the environment such as metals can select for AMR. Moreover, largescale mixing of human-associated- and environmental bacteria can promote the exchange of resistance genes between strains, providing the genetic substrate for selection. Recent work suggests that such horizontal gene transfer might occur at the same rate as mutation but the relative importance of these two fundamentally distinct genetic mechanisms in generating AMR is not known. In this PhD project, we will design experiments to quantify and compare the prevalence of point mutations versus horizontal gene transfer events in generating resistance. Using flow cytometry and genome sequencing, we will measure the type and rate of genetic change under different realistic pollution scenarios. These data will provide fundamental data on bacterial genome evolution but also provide a scientific basis for pollution management.

We have a great community of scientists on the Penryn Campus with many excellent collaborators in Exeter and in Bath as well. Plus Cornwall is a great place to live, as evidenced by this somewhat gratuituous photo.

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Eden Project: Invisible Worlds Exhibition

This is a bit overdue as the opening took place in May, but I still wanted to highlight the current Eden Project exhibition Invisible Worlds. This is a major new permanent exhibition that reveals the world beyond our senses: too big, too small, too fast, too slow, too far away in space and time. It includes plenty of interesting exhibits involving bacteria set up in collaboration with University of Exeter microbiologists based in Penryn, including collaborator Ben Raymond as well as Sean Meaden, the latter who is involved in practical workshops explaining fermentation organised by FOAM. The centrepiece of the exhibition is the sculpture “Infinity Blue” which depicts a cyanobacterium. The artists of Studio Swine who made it actually visited our lab to do some filming (although I am not sure if much ended up in the accompanying (beautifully shot) film).  The Invisible You exhibiton on the human microbiome that Will Gaze and I contributed to is also still available to see. I thoroughly recommend visiting, especially now the “rainy season” will start!

Michiel

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Paper out: Staphylococcus cornubiensis sp. nov., a new member of the Staphylococcus intermedius Group (SIG)

My colleagues Aimee Murray, Lihong Zhang and Will Gaze and I have an ongoing collaboration with colleagues from the Royal Cornwall Hospital John Lee and Richard Bendall on the detection of ‘Staphylococcus intermedius Group’ (SIG) in human infections. These bugs are associated with wildlife and pets but are also able to infect humans (they are ‘zoonotic’). I wrote a short blog post about this collaboration a while back, and see that I failed to mention the resulting publication in the Journal of Clinical Microbiology: “Improved detection of Staphylococcus intermedius Group in a routine diagnostic laboratory“. In it, we described a simple scheme to differentiate these Staphylococci from the very similar-looking and ubiquitous species Staphylococcus aureus. We isolated a number of Staphylococcus pseudintermedius clones in the 2015 study, but also had a weird outlier in the phylogenetic tree: isolate ‘NW1’. In the new paper, we sequenced the genome of this isolate and found it to be sufficiently distinct from the three known SIG species to deserve its own name. As the isolate came from a patient travelling from the North of England, Staphylococcus starkensis was floated, but the nomenclature editors at IJSEM found that a bit too flamboyant. Luckily we had a great alternative inspired by the Romans: Staphylococcus cornubiensis. Our isolate is phenotypically very similar to the other SIG species but it is genomically quite distinct, with an Average Nucleotide Identity of 90.2% with closest relative S. intermedius. Although pathogenic, NW1 carries no known virulence genes or mobilizable antibiotic resistance genes. We hope to obtain funding to conduct further studies to assess the prevalence of this species in humans as well as its potential presence in companion animals.

Aimee K. Murray, John Lee, Richard Bendall, Lihong Zhang, Marianne Sunde, Jannice Schau Slettemeås, William Gaze, Andrew J. Page, Michiel Vos (2018): Staphylococcus cornubiensis sp. nov., a new member of the Staphylococcus intermedius Group (SIG). International Journal of Systematic and Evolutionary Microbiology, doi: 10.1099/ijsem.0.002992

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