New science minister announces ‘war cabinet’ to tackle antimicrobial resistance on all fronts

*after much haranguing, finally another post from Will Gaze!*

Antimicrobial resistance (AMR) is a hot topic at the moment and the Natural Environment Research Council (NERC) recently issued a press release giving details of a cross-research council initiative to tackle the problem. On their website, they give seven case studies as examples of research funded by UK research councils. Work by both our lab and collaborative work at the University of Warwick makes up a significant part of the research showcased in the NERC press release. This demonstrates the importance of our work and more importantly the significance of the environmental dimension of antibiotic resistance.

Research in Will Gaze’s group, carried out by Dr Lihong Zhang (photo below, right) and PhD students Aimee Murray (foreground) and Anne Leonard (middle background), was used in the Biotechnology and Biological Sciences research Council (BBSRC) case study. Aimee is jointly funded by AstraZeneca and the BBSRC and is studying whether environmental concentrations of antibiotics excreted by people and animals can select for antibiotic resistance in polluted river catchments.penryn10

Lihong and Anne’s work was also mentioned in this section even though it was actually funded by the European Regional development Fund (ERDF) and the European Social Fund. They have shown that there is a significant human exposure risk to AMR bacteria in coastal bathing waters in England and Wales, including to clinically important genes that confer resistance to front line drugs. Andrew Balfour who is currently studying for an MRes in molecular microbiology at the University of Bath was also involved in this research during a summer voluntary work placement. He will be co-author on two publications which shows the value of voluntary lab work!

The NERC case study is also work connected to the group. Lihong and I used to work at the University of Warwick in Liz Wellington’s lab and the research discussed was done by a former PhD student, Greg Amos, who I co-supervised and Lihong mentored. Greg has done really well and has made some important discoveries on the impact of waste water treatment plants (WWTPs) on reservoirs of antibiotic resistant bacteria in rivers (Amos et al 2014). He is currently revising another paper submitted to ISME Journal, one of the top ecology / microbiology journals, which models the drivers of AMR reservoirs in sediment on a river catchment scale. We show that 50% of the prevalence of a molecular marker of resistance is associated with size, type and distance from WWTPs.The NERC case study been picked up by the press and is the subject of a NERC Planet Earth Article.

Will Gaze

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Paper out: Improvement in Staphylococcus and Bacillus strain differentiation by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry profiling by using microwave‐assisted enzymatic digestion

Quite a mouthful this title! It is in general a bit of an outlier paper for me, but I am very happy to have been involved. I have been interested in MALDI-TOF (matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry) as a tool for bacterial identification for quite some time. Basically (VERY basically), this method involves zapping a colony with a laser, catching the molecules that come flying off and creating a peak chart based on their velocity and charge, see the pic below. (This analysis focuses on the level of proteins, and so is an example of proteomics.) Different bacteria consist of different molecules and produce a different peak pattern. Specific peaks can be compared among strains, or overall peak patterns similarity can be compared by making a dendrogram.

MSA main reason why I became interested in MALDI-TOF, is that in theory, you could process a large number of samples for little money in little time. The standard way of typing a bacterial isolate is to sequence a marker gene, almost always 16S rRNA (sometimes a different gene, see also here). This approach takes time, as it involves performing a PCR, sending it out by mail for a company to do the actual sequencing, followed by manually checking sequence quality. It is also relatively costly: around £5 per isolate and ususally projects involve at least dozens of isolates. However, MALDI-TOF machines are very expensive, you need a good reference database (i.e. a collection of isolates that have both been sequenced and ‘MALDI’d’ to compare any new isolates with) and in general it might not be quite as quick, cheap and simple as manufacturers would have you believe.

I came in contact with Ondrej Šedo, Zbynek Zdráhal and colleagues in the Czech Republic quite randomly as is usually the case, and they very nicely to offered to type some strain collections for me. (It is in a way weird that you can collaborate and publish with people you have not even met btw.) Using a bit of internal funding from CEITEC (the Central European Institute of Technology) at Masaryk University in Brno, we followed this up by typing Bacillus isolates from two collaborators of mine in Ljubljana, Slovenia, Ines Mandić-Mulec and Polonca Štefanic. (I need to write a post about the work MSc student Anja Pecman from their lab has done in Penryn last year some time soon!) These Bacillus isolates are very closely related ecotypes (see here) and it would be very useful to be able to tell them apart using MALDI-TOF instead of checking a handful mutations in a marker gene or doing loads of phenotypic assays. The experiments done on these isolates suggest that it is indeed possible to delineate different strains belonging to the species level using relatively easy fixes to standard protocols.

Balážová, T, Šedo O, Štefanic P, Mandić-Mulec P, Vos M and Zdráhal Z. Improvement in Staphylococcus and Bacillus strain differentiation by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry profiling by using microwave‐assisted enzymatic digestion.” Rapid Communications in Mass Spectrometry 28.17 (2014): 1855-1861. link to free download

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two visitors

Last week, we had the pleasure to have Gabriel Perron (University of Ottawa) and Pål Jarle Johnsen (University of Tromsø) over for a visit. They both gave super seminar talks and took their time to interact with lab members. We also spent time discussing plans for a NERC pump priming grant with Amy McLeman on experimental evolution that has just started (see this old post), partly in the office and partly in the beautiful Gyllyngdune Gardens:

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OpenROV

I have had the pleasure to be involved with a small internal grant application that has now been rewarded, enabling the purchasing of an underwater robot! This particular Remotely Operated underwater Vehicle (ROV) is the ‘maker‘ community kickstarter project OpenROV. Leading the grant is BioSciences colleague Chris Lowe and we are lucky to have colleagues from Falmouth University‘s MAKERNOW digital fabrication lab involved: Justin Marshall, Andy Smith and Adam Stringer. We will first assemble (when I say ‘we’ I mean the makernow wizards…) and try out an openROV kit and based on this experience we aim to build another, improved version built from parts made from scratch and selected ordered parts. This will offer fantastic opportunities for student projects, outreach to the people of Cornwall and hopefully some marine biology research too. The ROV goes up to 100 meters deep, which is a good bit beyond recreational diving and so will allow a unique look at organisms up close in their natural habitat. As this work is out of the remit of the Medical School I hope to post updates on my rock pooling blog An Bollenessor (not affiliated with my work) later in the year.

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Camborne Science and International Academy student project

We had the pleasure to be visited by five students of the Camborne Science and International Academy for a lab project over the last few months. Jasmine, Amy, Kyle, Lauren and Georgina (flanked in the picture by Aimee and Amy) came in for two afternoons every fortnight (not the easiest schedule for a microbiology project!) to do some actual research in an actual research lab. They experienced the usual dose of failures (welcome to the world of research!) but also came across some interesting findings that we hope to build on later. In addition to learning about various questions and approaches in microbial ecology, they gained a lot of practical experience: autoclaving media, collecting environmental samples, isolating soil bacteria and classifying them by colony morphology, working with dilution ranges, setting up phage enrichment cultures, performing plaque assays and bacterial transformation assays. All in all I hope they gained some useful experience. (I think that even discovering that you do not really like this type of work is valuable, as at least you can cross one career path of the list and move on!)DSCN0164

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Bacteria vs. Animals

I mentioned a manuscript in a recent post written together with ECEHH colleague Will Stahl-Timmins on ‘The Secret Lives of Bacteria’. In this post, I wanted to highlight one of the figures from this paper highlighting the relationship between mass, generation time and genome size for a range of microbes and animals. It is clear that 1) these measures span an enormously large range (hence the logarithmic scales, so for the human example 104.8 g= 63 kg and a generation time of 105.3 h= 25 years) and 2) there seems to be a quite good positive correlation between the three parameters:

Fig2The data on genome sizes are easy to find on GenBank. However, there are still a lot of organisms without sequenced genomes; the largest animal that has ever lived, the Blue Whale, would have been a nice one to add. It is possible to construct a more extensive figure using the weight of genomes instead. The weight for haploid genomes is measured in picograms and is termed the C-value. This has been measured for a lot of organisms and databases exist for animals and plants. There is a conversion for DNA weight to number of nucleotides, for a Bottlenose Dolphin (there are no data for the Blue Whale) the estimated (haploid) genome size would be (0.978 x 109) x 3.3 pg= 3227 Mb (similar to that of humans).

Generation time equals doubling time in bacteria. For some other organisms this is a tricky one. Chlamydomonas for example can undergo two or three rounds of meiosis before division, resulting in four or eight daughter cells. Division and growth of course also depend on the quality of the environment.

Data for mass were easy to find for big animals, harder for insects (dry weight is often used, which makes sense as the weight of a mosquito will be very different before and after it has taken sips of your blood for instance) and difficult for bacteria. Cell lenght and width can be taken from EM images and using approximations for spheres and cilinders converted to volumes and mass when assuming cells mainly consist of H20. However, this is quite imprecise, as cells are not always spherical or cylindrical. Pelagibacter ubique is so small that 30% of its cell volume is taken up by DNA alone, changing density significantly. Moreover, cell shape and size can be quite variable (e.g. changing across developmental stages in Dictyostelium).

The differences between familiar vertebrates and bacteria (and a highly diverse range of organisms ‘inbetween’) are vast. The log scale might actually obscure these differences rather than emphasize them, but it is the only way to make such a plot.

P.S.

Mark van Passel recommended the nice webpage BioNumbers which is a catalogue of useful (and not so useful) numbers in biology. Bookmarked!

Michiel

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Marine/Pollution/Art

An interesting mini-exhibition in the ESI building featuring art made of plastic waste found on our shores. Bad and ugly things made beautiful. One big (3×3 meter) installation by Liz Franklin ‘Trawler Trash’ now hangs in the atrium:

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From the top: A guillemot woven from hundreds of washed up cable ties (Liz Franklin), lids, caps and bottle tops picked up by one person fro one hour at a local beach (Claire Wallerstein), thousands of shotgun wads, most probably from guillemot hunting on the Canadian east coast (Claire Wallerstein), two ‘trash heads’  (I do not know who made these, apologies). IMG_0773IMG_0770

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