How a motile cytoskeleton drives bacterial cell division

seamusIn a recent issue of Science, the discovery of a key mechanism for bacterial cell division was reported. This work was carried out by Dr Seamus Holden’s lab (ICaMB) in collaboration with Professor Cees Dekker (TU Delft), Professor Yves Brun (Indiana University), Professor Mike VanNieuwenhze (Indiana University) and Professor Ethan Garner (Harvard University). Here, Seamus tells us about this discovery and what its implications could be for antimicrobial research.

Bacterial cell division is a lovely mechanistic problem in biology: how do the simplest living organisms build a crosswall at mid cell, against very high outwards pressure (think of a racing bike tyre), without bursting?  A ring of protein filaments forms around the future division site, and enzymes associated with this ring build a new crosswall that cleaves the bacteria in half. But what has remained completely mysterious is how these proteins work together as a single nanoscale machine to cut the bacterial balloon skin (cell wall) in two.

Cytoskeletal proteins FtsZ in live bacteria imaged in vertical nanocages

Cytoskeletal proteins FtsZ in live bacteria imaged in vertical nanocages

Working together with collaborators in Delft, Indiana and Harvard, we tracked the organization and motion of key division proteins as they build the dividing crosswall, and the organization of the newly built crosswall itself. We began by examining the motion of FtsZ, a cytoskeletal filament that is required for cell division – cytokinesis – in bacteria and is related to the tubulin cytoskeletal protein found in eukaryotic cells. Using high-resolution microscopy techniques, we found that FtsZ filaments move around the division site, traveling around the division ring. We imaged the motion of individual cell wall synthesis enzymes, and saw that the synthesis enzymes ride on FtsZ filaments, building new cell wall as they travel along the division site. This causes the cell wall to be synthesized in discrete sites that travel around the division site during cytokinesis, a process which we were able to observe directly by using dyes that label the bacterial cell wall. Using a variety of experimental techniques, we were able to speed up or slow down how fast FtsZ rotated around the cell. Strikingly, we found that the speed of FtsZ filament motion determines how fast the cell can divide. When FtsZ moves more rapidly, cell wall is produced more quickly, and cytokinesis happens faster. This shows that the motion of FtsZ is the critical overall controller of cell division.

One challenge that we faced was trying to look at the division proteins in actively dividing cells. At the earliest stages of division, it was possible to image division protein organization because the proteins in the partially assembled ring are sparsely distributed. However, a new strategy was required to measure how the dense protein network of actively dividing cells was organized. Normally, bacteria are immobilized flat on a microscope slide, and imaged from underneath, but unfortunately this places the division ring side-on, obscuring the motion and organization of division proteins. To solve this problem, we used nanofabrication technology, originally developed to manufacture computer chips, to create tiny gel nanocages to trap bacteria in an upright position.

Bacteria trapped in vertical nanocages

Bacteria trapped in vertical nanocages

By trapping individual bacteria upright, we were able to rotate the cell division ring so that it was fully visible on our high resolution microscope. This revealed the dynamic motion of FtsZ filaments as they travel around the entire division site:

Together, these results revealed the basic mechanistic principles of bacterial cell division: that the building of the division crosswall is orchestrated by moving cytoskeletal filaments.  Previously, the cytoskeleton was thought to serve as a static scaffold, recruiting other molecules and perhaps exerting some force to divide the cell. This new work demonstrates that all the components of cell division are in constant, controlled motion around the division site, driven by the fundamental dynamics of the cytoskeleton.

In the longer term, this study could open up novel antibiotic targets. Based on the discovery that the treadmilling motion of the bacterial cytoskeleton is critical for division, it may be possible to develop new drugs that specifically inhibit this motion, similar to how the chemotherapy drug taxol suppresses the motion of the cytoskeleton in cancer cells.

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Links

Explanatory animation: https://youtu.be/6dq2_gqKPfU (Animation credit TU Delft / Scixel)

Nanocage Video: nanocage-movie-2.

Science report: http://science.sciencemag.org/content/355/6326/739

Press release: http://bit.ly/2kwsnJf

Origins of life in Newcastle

ICaMB’s Prof Jeff Errington organised and hosted an impromptu symposium on the origins of life at the Centre for Bacterial Cell Biology (CBCB) on Wednesday 18th January 2017. About 80 people attended, hearing 11 talks from a mixture of Newcastle and international speakers, including a number of guests who had travelled over from Japan for the meeting. The program was arranged more or less in “chronological” order, starting with the origins of the solar system 4-6 billion years ago, and ending (still almost 2 billion years in the past) with the emergence of the eukaryotes. The meeting sparked several very lively discussions, perhaps reflecting the difficulty of doing standard hypothetico-deductive experiments on the topic, in the absence of time travel technology! Nevertheless, the day was a great success and is likely to lead to new international collaborations and funding opportunities.

By Jeff Errington

My emerging interest in the subject has two origins. First, through ageing and trying to find a reason for existence before existence disappears! Second, the lab’s work on L-form bacteria (see Box), which has attracted much interest from the origins of life scientific community.

L-form bacteria use a seemingly primitve mechanism of replication.

L-form bacteria use a seemingly primitive mechanism of replication. L-forms are cell wall deficient bacteria, which turn out to replicate by a slightly bizarre, seemingly haphazard mechanism involving membrane blebbing and tubulation. The process provides a model for how primitive life may have proliferated billions of years ago, before the invention of the cell wall.

 

The latest findings have led to a number of fascinating new scientific contacts, and about a year ago, Prof Shige Maruyama, who heads a major Japanese research institute dedicated to origins of life work called the Earth-Life Science Institute (ELSI), made contact, proposing discussion around possible collaborations. After a series of small meetings in Newcastle and my visit to Tokyo, momentum began to emerge, culminating with the proposal for a major workshop in Newcastle, with half a dozen or so ELSI members planning to attend.

Prof Shige Maruyama, ELSI, Tokyo, Japan

Prof Shige Maruyama, ELSI, Tokyo, Japan

As discussions developed, I identified various experts in Newcastle with complementary expertise and interests in the general area, and the idea for a full blown symposium took shape. There was even time to identify a top class international “guest” speaker, Prof Bill Martin from Dusseldorf, who came over at short notice to give the concluding talk.

This is not the place to go through each talk in detail. However, from my perspective, what I hope people took away from the meeting would have included the following general points.

First, the problem is amazingly multidisciplinary, with important contributions from astrophysicists, geochemists, organic chemists, microbiologists (structure/function, metabolism and physiology) and evolutionary bioinformaticians. Second, we still have a very hazy understanding of many of the early events in the earth’s planetary history, e.g. when did the water arrive and how much? Third, it is clear that microbes were responsible for huge changes in planetary chemistry, particularly oxygenation but also that planetary composition must have reciprocally influenced microbial evolution.

Prof Bill Martin, Dusseldorf, Germany

Prof Bill Martin, Dusseldorf, Germany

The day concluded with a very nice dinner at the Jesmond Dene House Hotel, supported by Newcastle University and hosted by Pro-Vice Chancellor Prof Nick Wright. I’m sure that the original owner of the house, Lord Armstrong, would have approved of the day (for example, I gather that his company won the contract to build ships for the Japanese Navy 120 or so years ago). I’m also sure that as a Fellow of the Royal Society (elected in 1843) he would have been acquainted with Charles Darwin and perhaps they too had interesting conversations about the origins of life in their own time frame.

Determination is key – Prof Ramakrishnan’s Baddiley Lecture

By Kevin Waldron.

Last week saw ICaMB host the latest in our series of Baddiley lectures, which commemorates Professor Sir James Baddiley (1918-2008). Baddiley was a distinguished Professor at Newcastle University (1954-81) and a Fellow of the Royal Society (elected 1961) who made numerous important fundamental discoveries in microbiology, not least the discovery of teichoic acids, cell wall components in Gram positive bacteria.

Jeff Errington introduces Venki Ramakrishnan to the ICaMB audience

Jeff Errington introduces Venki Ramakrishnan to the ICaMB audience

Baddiley’s work on the fundamental processes of bacteria, including the structure and function of components of the bacterial cell wall, is continued to this day in Newcastle through the work of members of ICaMB’s Centre for Bacterial Cell Biology (CBCB). Although James Baddiley died shortly after the first in ICaMB’s series of Baddiley lectures, we were delighted that the Baddiley family was again represented at this year’s lecture by James’s son, Christopher Baddiley.

This year’s guest speaker was Professor Sir Venki Ramakrishnan, distinguished research leader and Deputy Director of the Laboratory of Molecular Biology in Cambridge, Nobel laureate and newly-elected President of the Royal Society. With all of the demands on his time that come with this new role as President, the large audience that gathered on Friday afternoon were grateful that Venki was able to find time to visit Newcastle to deliver his lecture. As ever, both the lecture and the surrounding celebration was expertly organised and introduced by CBCB Director, Professor Jeff Errington.

Venki illustrates the structure of the yeast mitochondrial ribosome

Venki illustrates the structure of the yeast mitochondrial ribosome

Venki’s lecture gave a brief history of his atomic-resolution structural studies of the ribosome, the macromolecular nucleoprotein complex that converts the four-letter genetic code in nucleic acid into the twenty-letter amino acid code in proteins. He presented detailed structural models of eukaryotic ribosomes, derived from X-ray crystallography and cryo-electron microscopy data accumulated over 30 years of detailed study in his laboratory.

We asked some of ICaMB’s early career researchers to describe their impression of Venki’s lecture:

“Professor Venki Ramakrishnan was kind enough to deliver this year’s Baddiley lecture. It was an honour to meet Venki, who somehow managed to fit us in between Royal Society committee meetings and a chat with the Science minister! He impressed us all with a phenomenal talk discussing how he solved the structure of the mitochondrial ribosome using cryo electron microscopy. Wow – cryo EM has truly moved beyond blob-ology! One thing that really struck me about Venki is how humble he is; despite being so incredibly successful and lauded, there’s not a trace of ego on the guy; something for us all to aspire to.”

Venki illustrates how the ribosome works

Venki illustrates how the ribosome works

Seamus Holden, University Research Fellow

“It was incredibly cool to hear about Venki’s work first hand. The enormity of his achievement became clear when he showed a single slide with the dozens of conformations of the ribosome’s catalytic cycle and indicated that there were structures available for the majority of them! And what was humbling was that Venki did not seem at all interested in dwelling upon his past successes. Rather, he briskly moved past this slide onto his current work regarding mitochondrial ribosomes which was both cutting-edge but also somewhat raw because of its novelty. I found it inspiring to see a scientist of his stature still so driven to continue discovering and learning.”

Post lecture, Venki holds the gift he received from his hosts at ICaMB

Post lecture, Venki holds the gift he received from his hosts at ICaMB

Heath Murray, Royal Society URF

“For me Venki’s journey was an excellent advert for never giving up. Often as researchers (particularly at the start of our careers) we are encouraged to know when to call time on a set of experiments that are bogged down and not yielding answers. Pursuit of the next grant and the speed of some of our competitors unfortunately make it risky to continue to spend years and years believing in the same project that fails to show progress relatively quickly. Yet what an example Venki is, many years and many postdocs focusing on the same problem, persistence and belief in himself and his team has more than paid off. Inspirational.”

Suzanne Madgwick, Wellcome Trust Career Re-entry Fellow

A novel copper storage protein discovered by ICaMB scientists

In a recent issue of Nature the discovery of a new family of proteins that store copper ions inside bacterial cells was reported. This work was carried out by Prof. Chris Dennison’s lab (ICaMB) in collaboration with Dr. Kevin Waldron (ICaMB), Dr. Arnaud Baslé (ICaMB), Dr. Neil Paterson (Diamond Light Source) and Prof. Colin Murrell (UEA). Here, Kevin tells us about this discovery and what its implications could be for the biotechnological exploitation of methane.

Methane, the main component of natural gas, is produced by both geological and anthropogenic processes on Earth, and can be released into the atmosphere. The biosphere’s primary mechanism for limiting the amount of methane (a powerful ‘greenhouse gas’) that escapes into the atmosphere is through its consumption by methane-oxidising bacteria, or methanotrophs (literally ‘methane-eating’), who utilise methane as both a carbon and energy source.

Transmission electron micrograph of a M. trichosporium OB3b cell showing the intracytoplasmic membranes that house the copper-dependent enzyme pMMO.

Transmission electron micrograph of a M. trichosporium OB3b cell showing the intracytoplasmic membranes that house the copper-dependent enzyme pMMO.

The key enzyme that methanotrophs use to oxidise methane to produce methanol is called methane monooxygenase (MMO). Almost all methanotrophs possess a membrane-bound form of MMO that requires copper (Cu) for activity, called pMMO (some strains also possess an iron-requiring alternative soluble enzyme, called sMMO). Therefore, these bacteria have an unusually high demand for copper, a metal that is essential for most organisms but is used rather sparingly, mainly because it can also be extremely toxic.

Previous studies of methanotrophs have revealed that they utilise unusual mechanisms for acquiring the copper they need for pMMO. For example, they produce and secrete a small, modified peptide called methanobactin that is involved in high affinity copper uptake, analogous to the more familiar siderophore iron uptake systems.

The model methanotroph, Methylosinus trichosporium OB3b, was analysed in the hope of uncovering novel copper proteins. Soluble extracts were resolved by two-dimensional liquid chromatography, with the copper content of resulting fractions monitored. The most abundant copper pool was found to contain a small, cysteine-rich protein that had not been studied previously and Chris Dennison (PI) and I (Co-I) obtained a BBSRC grant to investigate this and related proteins.

The presence of 13 cysteine residues in a mature protein (after cleavage of its signal peptide) with only 122 amino acids was immediately significant, as its thiol sidechain is often found in copper-binding sites. The recombinant protein was extensively studied using a suite of biochemical and biophysical methods to determine its in vitro properties This novel tetrameric protein is capable of binding up to 52 Cu(I) ions with high affinity, consistent with a potential role in the storage of this essential metal and was therefore named Csp1 (copper storage protein 1). A mutant strain of M. trichosporium OB3b that lacks this Csp1 protein (as well as a closely-related protein, Csp2) shows a phenotype consistent with a copper storage role of these proteins in vivo.

The crystal structure shows that the apo-monomer adopts a well-characterised four-helix bundle motif with all 13 cysteine sidechains pointing into the core of the bundle. The protein structure is essentially unchanged in the presence of copper, except that the core of each monomer has filled with 13 Cu(I) ions, bound by the cysteine sidechains. This is an unprecedented structure for metal storage.

The structure of the Cu(I)-Csp1 tetramer, with the 13 Cu(I) ions bound within the core of each four-helix bundle shown as orange spheres.

The structure of the Cu(I)-Csp1 tetramer, with the 13 Cu(I) ions bound within the core of each four-helix bundle shown as orange spheres.

The implications of this discovery could be of wide impact. There is a great deal of interest in using methanotrophs and MMOs in industrial biotechnology. Available methane is on the increase due to ‘fracking’, but importantly methane can also be produced from sustainable sources such as through the degradation of biomatter (biogas). Methanotrophs and the MMOs could in future be exploited using synthetic biology approaches for gas-to-liquid conversion, for the production of liquid fuels as well as bulk and fine chemicals from renewable methane.

Any such biotechnological applications require an understanding of how the production of pMMO is regulated and how this complex enzyme is assembled, including the cellular delivery and insertion of the essential copper cofactor. The work published in Nature shows that Csps are an important piece in that assembly jigsaw.

Furthermore, bioinformatics has shown that cytosolic members of the Csp family are also encoded in other bacterial genomes. Most bacteria are thought not to require copper in their cytoplasm, so the presence of cytosolic Csp homologues in their genomes could re-write our basic understanding of their use and homeostasis of copper.

Links:

Nature article: http://www.nature.com/nature/journal/v525/n7567/full/nature14854.html

News & Views: http://www.nature.com/nchembio/journal/v11/n10/full/nchembio.1918.html

BBSRC website: http://www.bbsrc.ac.uk/news/fundamental-bioscience/2015/150827-pr-bacteria-that-could-protect-our-environment/

ACS Chemical & Engineering news: http://cen.acs.org/articles/93/web/2015/08/Protein-Stores-Copper-Methane-Digesting.html

Press release: http://www.ncl.ac.uk/press.office/press.release/item/could-bacteria-help-protect-our-environment

Another Cell-ebration

Heath MurrayKevin WaldronLast year we brought you details of the inaugural CBCB Symposium. In July the second CBCB symposium was held, and today we hear from the organisers, Kevin Waldron and Heath Murray, about this latest successful event.

The idea for an annual Centre for Bacterial Cell Biology (CBCB) symposium was originally conceived in 2013, and aimed to showcase both the high quality and the immense breadth of research activity that goes on in this unique Centre. It would also be an excellent opportunity to bring together the CBCB research community based in both the Medical School and in the Baddiley-Clark building to discuss their work and build future collaborations.

It wasn’t long after our 2014 Symposium was over when the organising team (Bernie Shaw, Heath Murray, Kevin Waldron and Jeff Errington) began planning for this year’s second event. Obviously we were delighted with the success of that first meeting, but of course it also applied a little pressure on us as organisers; this year’s event had to achieve a similar level of success. Fortunately, the feedback we had received from the 2014 event included a number of constructive suggestions from the CBCB community about how we might be able to improve the Symposium, and we tried to incorporate as many of these ideas as possible.

One of our postdoctoral researcher speakers, Yoshi Kawai, addresses the Symposium audience on the subject of L-forms

One of our postdoctoral researcher speakers, Yoshi Kawai, addresses the Symposium audience on the subject of L-forms

One suggestion was to include a number of more junior speakers in the Symposium Programme as well as PIs, and we are grateful to those postdocs who volunteered to present their work to the CBCB audience. Alexander Egan told us about his research in the Vollmer lab on the proteins that coordinate biosynthesis of the cell envelope during growth and division. Yoshi Kawai of the Errington lab explained  how L-forms, bacteria that lack their cell wall, can be produced in the lab and how they propagate in a manner independent from the known bacterial cell division machinery, as well as speculating on their implications for early life forms on Earth. Marcin Dembek of the Salgado lab contrasted the mechanisms that govern sporulation in Clostridium difficile, a pathogen that primarily causes infections via spores, and the model organism Bacillus subtilis. Finally Didier Ndeh described his research in the Gilbert lab on how gut bacteria degrade the most structurally complex dietary polysaccharide known, rhamnogalacturonan II. PI speakers covered further topics relating to antibiotic discovery and their mechanisms of action and synthetic biology.

In addition to our CBCB researchers, we also again invited two high-profile external speakers. The day started with Mark Leake (University of York) who told us about his research using state-of-the-art microscopy for in vivo imaging of single molecules within the bacterial cell. And the Symposium was concluded by John Helmann (Cornell University) on the subject of transcriptional stress responses in one of CBCB researchers’ favourite model organisms, Bacillus subtilis.

Poster prize winner Lauren Drage

Poster prize winner Lauren Drage

Another of the suggestions that we incorporated into the Symposium schedule this year was a poster session, which was accompanied by light refreshments (of course!) immediately after the day’s talks. We had a great turnout, with more than 20 posters on display, and the session generated a lot of lively scientific discussion. Again the Symposium organisers are very grateful to all those members of CBCB who participated in the poster session. We awarded three poster prizes, with congratulations to winner Lauren Drage for her excellent poster describing her research in the Aldridge lab looking for biomarkers for diagnosis of urinary tract infections, and to our two runners-up, Martin Sim (Wipat lab) and Clare Wilson (Errington lab); and of course thanks to our poster judges, Lucy Eland and Yulia Yuzenkova.

Finally, we all got to enjoy an informal barbecue dinner and drinks, where the science discussions could continue into the evening.

Jeff Errington and John Helmann in post-symposium discussions

Jeff Errington and John Helmann in post-symposium discussions

Planning has already begun for next year’s Symposium, which will be held on the 8th July 2016, and will feature two more external keynote speakers, Christine Jacobs-Wagner (Microbial Sciences Institute, Yale University) and Prof. Tracy Palmer (Molecular Microbiology, University of Dundee). We welcome your feedback too, so if you attended this year’s Symposium and you have any suggestions about how we might improve next year, please let us know.

The gender agenda: ICaMB welcomes the Athena Swan debate.

If you work in academia, then undoubtedly you will have heard something about the Athena SWAN charter over the last year or so. Athena SWAN is a national scheme that aims to rebalance the gender ratio in higher education and research, with a particular focus on employment in the STEMM (science, technology, engineering, maths and medicine) subjects. Like other research institutes, ICaMB has been engaged in this initiative, and were delighted to receive a bronze award when the results were recently announced.

However, Athena SWAN is not without its controversies. Although most (if not all) academics agree that the gender imbalance is a problem, not everybody agrees on the causes or on the best way to fix it. New research is published on the gender gap every week, but even this can prove contradictory (see for example here, here, here and here).

Today, we get two different personal opinions on Athena SWAN from members of the ICaMB Athena SWAN Self-Assessment Team. First, we hear from Suzanne Madgwick, who says she doesn’t feel she has experienced the kind of discrimination that is often posited as a major cause of academic gender inequality.

Next we get the view of Nancy Rios, who tells us more about the gender imbalance, the Athena SWAN charter, how ICaMB has responded to it and what kind of changes can be put in place to make a positive impact.

On the ICaMBlog team, we are aware that this issue is not without controversy. However, we believe that the best way forward, as we proceed towards applying for silver and ultimately gold Athena SWAN status, is to have an open debate about these issues. We’d like to hear your opinions on this subject and are keen to hear from anyone who would also like to write an article on this subject. Please leave a comment below and join the conversation.

Happy Birthday PAN!C

PAN!C-Birthday

PAN!C-BethBy Beth Lawry

ICaMB’s postgraduate student association (PAN!C) celebrated it’s 2nd birthday in February. Thank you to all 40+ of the ICaMB postgraduate students who came and enjoyed our night of celebrations!

Yep, if you’re an ICaMB postgraduate student, I’m the one who clogs up your inbox with emails about yet another PAN!C activity. The past few years, since Claire Whitworth and Kerrie Brusby began the ICaMB postgraduate association, have been an amazing whirlwind. To celebrate PAN!C’s birthday I thought I’d share my highlights with you.

PAN!C CV Workshop, June 2014

PAN!C CV Workshop, June 2014

In February 2013, PAN!C applied for and won a University Innovation Grant, and were invited to celebrate with the Vice Chancellor. These funds have enabled PAN!C to host numerous events, both academic and social, for ICaMB’s PhD student community. In November 2013 we hosted our careers symposium. Of course, we’ve all been given the usual, generic career options for people with PhDs, but that wasn’t enough for PAN!C. We wanted our students to have the opportunity to hear about careers they perhaps had not thought of, and provide the chance to meet professionals in these areas…. We even had an interesting insight into running a pole dancing business! In 2014, PAN!C hosted a CV workshop, with experts providing information on how to improve and tailor your CV to a variety of sectors. We had 12 speakers, and over 60 students attended the day.

PAN!C Climbing, February 2014

PAN!C Climbing, February 2014

Both the Careers Symposium and CV workshop received extremely positive feedback, from students and speakers alike, with 100% of responders stating they’d recommend the workshops. It’s worth noting that, while organising these events, I made contacts with people from industry, teaching, law, business and recruitment, all of whom I’m still in touch with. PAN!C has provided me with a fantastic opportunity to network with my peers, and gain skills in team work, grant applications, leadership and communication.

PAN!C are crowned FMS quiz champions, May 2014

PAN!C are crowned FMS quiz champions, May 2014

On the social side, PAN!C has always strived to bring together the many groups within ICaMB. Together we’ve conquered our fears and climbed to dizzying heights at the Newcastle Climbing Centre, skated on ice at the Centre for Life in a somewhat Bambi fashion, hit a pin or 2 whilst bowling at MFA Bowl and became Quiz Champions of FMS!

Another highlight was the PAN!C Bake Off, where I almost fell into a sugar induced coma!….. mmmmm cake. And along the way we raised a massive £361.56 for charity (which was split between Macmillan, Doctors without Borders and Age UK).

PAN!C-Cake

Fabulous cakes at the PAN!C Bake Off, September 2014

Since forming, the PAN!C committee has had 10 members, and I’d personally like to thank every one of them for contributing and making this association such a fantastic and fun thing to be a part of. I’d also like to thank the ICaMB postgraduate students too. We’re a student led committee for the students and without you we’re nothing!

I’m nearing the end of my stint at Newcastle University, so it’s time to pass the PAN!C reigns over. It’s something that has improved my time management and helped me to focus on my PhD work. I hope you too realise the opportunity that PAN!C offers. You can give as little or as much time as you like, involve yourself with conference organising or just attend the socials. So, get involved and let’s keep the party going!

If you want any further information or just to chat about PAN!C, please don’t hesitate to contact me: b.m.lawry@ncl.ac.uk.

Beer, Bread and Bacteria

 

Prof. Harry Gilbert

Prof. Harry Gilbert

The diverse organisms that live in our gut, collectively termed the gut microbiota, can have a major impact on our health. A new paper from Prof. Harry Gilbert’s lab in ICaMB, published today in Nature, shows that one member of our gut microflora uses a ’selfish’ mechanism to degrade a component of the cell wall of the yeast in our diet.

By Drs. Elisabeth Lowe and Fiona Cuskin.

Have you over-indulged this Christmas? One too many ales, or too many turkey sandwiches?

Beer: full of yeast.

Beer: full of yeast.

The good news is that, while your waist line may be expanding and you may be feeling a little the worse for wear, the organisms of your gut microbiota are thriving!

Some of the bacteria in the human gut, called Bacteroides, can break down the complex carbohydrates in our diet into simple sugars, which they use for energy.

Bread: full of yeast
Bread: full of yeast

 

Our work, published in Nature today, shows that one of these bacteria can also break down some of the carbohydrate cell wall of yeasts, called mannan, a polymer of mannose. This includes mannan from Saccharomyces cerevisiae (Baker’s yeast), and the pathogenic gut fungus, Candida albicans. The current understanding of polysaccharide digestion by gut bacteria suggests a cooperative environment, in which break-down products are shared between different members of the microbiota. However our data shows that this species (Bacteroides thetaiotaomicron) is ‘selfish’ when it degrades mannan, and doesn’t share any of the digestion products with other bacteria.

Turkey: er... full of yeast?

Turkey: er… full of yeast?

To achieve this selfish degradation, the large and multiply-branched mannan structure undergoes only very limited degradation in the extracellular space (see figure). The resulting processed mannan fragments are then imported into the Bacteroides periplasmic space, where they are further degraded by a suite of glycoside hydrolase enzymes to yield the sugar mannose. Achieving complete breakdown within the periplasm prevents  the mannose from being shared with competing bacteria.

This selfish approach to mannan utilisation could offer the opportunity to design bespoke prebiotics targeted to a specific bacterial population within the gut. Food products containing yeast mannan would be expected to promote growth of B. thetaiotamicron, whereas other complex polysaccharides may specifically promote other members of the microbiota.

Complex polysaccharide mannan is sequentially degraded by a 'selfish' mechanism to yield periplasmic mannose.

Complex polysaccharide mannan is sequentially degraded by a ‘selfish’ mechanism to yield periplasmic mannose.

A number of inflammatory bowel diseases such as Crohn’s disease are associated with intolerance to yeast, and particularly cell wall polysaccharides, and have also been linked to low levels of Bacteroides species in the gut. Our work provides a potential mechanism for how Bacteroides might be able to influence the effect of yeast on patients with Crohn’s disease, and in fact a drug named Thetanix (which is a live formulation of Bacteroides thetaiotaomicron) has been licensed for treatment of paediatric Crohn’s disease in the USA.

Researchers Max Temple, Lis Lowe and Fiona Cuskin of the Gilbert lab.

Researchers Max Temple, Lis Lowe and Fiona Cuskin of the Gilbert lab.

Yeast is commonly in our diet in the form of some of our favourite things: bread, beer, wine and fermented food products.  So it may be dry January but if your willpower fails and you succumb to an alcoholic beverage, then make sure it’s an unfiltered one with plenty of yeast!

This research in the Gilbert lab was funded by the Wellcome Trust and the European Research Council.

Links:

Nature article: http://www.nature.com/nature/journal/v517/n7533/full/nature13995.html

Press release: http://www.ncl.ac.uk/press.office/press.release/item/beer-and-bread-yeast-eating-bacteria-aid-human-health

Gilbert Lab: http://www.ncl.ac.uk/camb/staff/profile/harry.gilbert

 

A CBCB Cell-ebration

Heath MurrayKevin WaldronEarlier this month, the Centre for Bacterial Cell Biology held its inaugural Symposium. Here, the CBCB’s Heath Murray and Kevin Waldron tell us about what happened at the event.

One of the aspects of ICaMB that makes it a unique institute is the Centre for Bacterial Cell Biology (CBCB), a group of researchers who are focused on understanding fundamental biological questions using bacteria as model organisms. The CBCB was founded by Professor Jeff Errington FRS and is the world’s first major research centre with a focus on bacterial cell biology. Since its inception, CBCB has relocated to a purpose-built £30 million facility in the Baddiley-Clark Building, and has grown to include more than 20 different research groups. In a relatively short time, CBCB members have made outstanding contributions to our understanding of numerous aspects of fundamental cellular processes in a wide range of bacteria.

Prof Kenn Gerdes from the CBCB discusses how bacteria can form dormant variants that evade the immune defence response.

Prof Kenn Gerdes from the CBCB discusses how bacteria can form dormant variants that evade the immune defence response.

In order to recognise the success and the breadth of science being generated in the Centre, we recently held the inaugural CBCB Symposium on July 9-10. More than 120 members of the CBCB community participated in the two-day event, underscoring the critical mass of researchers at Newcastle University working within the field. This excellent turnout certainly contributed to the overall success of the event.

Research themes covered by talks from group leaders in the CBCB included sporulation, infection, persistence, biofilms, metabolism, motility, and morphogenesis. We also heard about the emerging subject of synthetic biology, where bacterial organisms will be programmed much like computers to perform discrete biological tasks.The CBCB Symposium was highlighted by inspirational talks from three distinguished external scientists, Jan Löwe (Laboratory of Molecular Biology, Cambridge), Mervyn Bibb (John Innes Centre, Norwich), and Simon Foster (Department of Molecular Biology and Biotechnology, Sheffield).

Prof Simon Foster explains how the superbug Staphylococcus aureus grows and divides.

Prof Simon Foster explains how the superbug Staphylococcus aureus grows and divides.

Professor Löwe discussed his work using a range of biochemical and structural approaches to analyse the bacterial cell division and morphogenesis machinery. Professor Bibb explained how his lab utilises a combination of next generation DNA sequencing and bioinformatics with classical genetic analysis to discover novel antibiotics. Professor Foster showed how studies on the fundamental aspects of bacterial cell biology can be harnessed to better understand host-pathogen interactions that can eventually be translated into vaccine development, with his focus on the ‘super bug’ Staphylococcus aureus..

Participants hold discussions over dinner and drinks following the Symposium.

Participants hold discussions over dinner and drinks following the Symposium.

At the end of the Symposium participants gathered together for dinner and drinks in the informal setting of the Forum. This provided an interactive end to the event that allowed researchers throughout the CBCB to meet one another, discuss the amazing science, and develop connections.