We're delighted our work with colleagues at the University of East Anglia and the Quadram Institute has been published.
Using faecal microbiota transplants in mice, we have shown that giving the gut microbiota of old mice to young mice has measurable effects on the central nervous system. This work has important implications for understanding how aging and the microbiota influence neurological function, and may allow us to develop methods to target the microbiota to assist 'healthy aging'. Watch the video below to find out more about this exciting work!
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Trimeric autotransporter adhesins (TAAs) are a family of surface proteins from Gram-negative bacteria. As their name implies, these proteins mediate binding of the bacteria to a variety of surfaces, including host cells and matrix components, abiotic surfaces, and other bacteria. This latter ability is called autoaggregation, which is a widespread phenomenon among bacteria and confers protection against environmental threats. The autoaggregation mediated by TAAs is homotypic, i.e. the TAAs bind to themselves.
In a recent paper, Jack C. Leo and colleagues have investigated whether TAAs can also mediate heterotypic binding to other types of TAAs. This would lead to co-aggregation of bacteria producing different TAAs. To do this, Leo and colleagues genetically engineered laboratory Escherichia coli to produce a specific type of TAA as well as a fluorescent marker protein, either red or green. Using microscopy and software prepared for this study, the researchers quantified the interactions between two populations of bacteria producing the same (autoaggregation) or different TAAs (co-aggregation). The results show that different TAAs can mediate co-aggregation, and generally the degree of co-aggregation correlated with the sequence similarity between the interacting TAAs. However, in some cases, two TAAs excluded each other, and aggregates of only one type of bacteria were formed. These findings have implications for the ecology of bacteria: co-aggregation is often a sign of co-operation between bacteria, whereas exclusion might indicate competition. Khalil HS, Øgaard J, Leo JC. Coaggregation properties of trimeric autotransporter adhesins. MicrobiologyOpen. 2020;doi:10.1002/mbo3.1109. In their recently published review, Rachel Whelan, Gareth McVicker and Jack C. Leo from the AROM group delve into the relationship between type 3 secretion systems (T3SSs) and type 5 secretion systems (T5SSs), providing an in-depth analysis of their roles in adhesion, invasion and their collaborative role in pathogenesis in Gram-negative bacteria. T3SSs form a syringe-like structure able to transport effector proteins into the host cell. T5SSs, also referred to as autotransporters, are known for their independent transport to the bacterial cell surface where they carry out a diverse array of functions, ranging from adhesion to immune evasion. This review discusses the interplay between the T3SSs and T5SSs that aid pathogenesis of some of the most well studied enteropathogenic organisms such as the Yersiniae, Shigella spp., enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. The pathogenesis of these organisms relies heavily on the two secretion systems acting collectively to achieve virulence, resulting in host cell invasion, intra- and inter-cellular motility and evasion of the immune response, leading to changes in the host cell cytoskeleton which is central to disease.
Whelan R, McVicker G, Leo JC. Staying out or going in? The interplay between type 3 and type 5 secretion systems in adhesion and invasion of enterobacterial pathogens. Int J Mol Sci. 2020;doi:10.3390/ijms21114102. Supervised by Dr Jody Winter, this paper describes work that was completed by Ben Murray and Robin Dawson (former MRes students at NTU who undertook research projects in the AROM group) and Lolwah Alsharaf, who is currently writing up her PhD thesis. They found that outer-membrane vesicles produced by Helicobacter pylori can help to protect the bacterium against hydrogen peroxide and some antimicrobial agents.
Murray B, Dawson R, Alsharaf L, Winter J. Protective effects of Helicobacter pylori membrane vesicles against stress and antimicrobial agents. Microbiology. 2020;doi.org/10.1099/mic.0.000934. Yersinia ruckeri is a fish pathogen, causing an infection called enteric redmouth disease that affects mostly salmonid fish. The disease causes significant losses in the aquaculture industry. Like most bacteria, Y. ruckeri survives in the environment by forming biofilms. These are multicellular bacterial communities embedded in a slimy extracellular matrix composed of a variety of different molecules.
In their newly published study, Jack C. Leo and colleagues investigated the role of two surface proteins in biofilm formation in Y. ruckeri – Y. ruckeri invasin (YrInv) and Y. ruckeri invasin-like molecule (YrIlm). They had identified these proteins previously and, based on their similarity to adhesins from other bacteria, assumed both mediated attachment of Y. ruckeri to surfaces. Knocking out the genes coding for these proteins individually significantly reduced the ability of Y. ruckeri to form a biofilm on several different types of surface, including many used in aquaculture (PVC, steel and polystyrene). When both genes were knocked out, Y. ruckeri barely formed any biofilm. Larvae of the greater waxmoth (Galleria mellonella) were used to test whether YrInv and YrIlm also played a role in causing disease. Y. ruckeri strains unable to produce one or both proteins had to be used at much higher infectious doses than the wild-type strain to kill the larvae. Overall, this study demonstrates that YrInv and YrIlm are adhesins of Y. ruckeri that promote biofilm formation and virulence. As such, they are potential targets for vaccine development or measures to control biofilm formation by Y. ruckeri in an aquaculture setting. Wrobel A, Saragliadis A, Pérez-Ortega J, et al. The inverse autotransporters of Yersinia ruckeri, YrInv and YrIlm, contribute to biofilm formation and virulence. Environ Microbiol. 2020;doi:10.1111/1462-2920.15051. On 15 February 2020 staff and students keen on microbiology and outreach braved the wind and rain to entertain and educate visitors to the Nottingham Festival of Science and Curiosity from 10 am to 4 pm in the Victoria Centre market area. This year we were accompanied by "Geralt the Germophobe" our now 3-D body target for our activity on helpful and harmful bacteria. Visitors selected volunteer fluffy bacteria to throw at Geralt and then discovered what nice or nasty bacterium made its home in the location they had hit. After a brief explanation as to what the bacterium could do either for or against humankind each visitor received a "non top trump" card with the bacterium’s statistics and unique artwork, as well as a stylish networking sticker "Hallo my name is ...." emblazoned with the name of their newly adopted microbial friend. There was then the opportunity to learn the importance of cleaning your teeth and not eating sweets before bed, as visitors could interact with our highly accurate biofilm model – carefully crafted from packing material and cheap hair gel. Having discovered that bacteria are much harder to remove from teeth when in a biofilm produced by conversion of sucrose to a sticky polymer, visitors were informed in breathless tones that during the night bacteria wee in your mouth while you sleep. Not at all traumatised by this they left, presumably to go buy some mouthwash and toothpaste. :-) These activities were delivered by members of staff from the NTU microbiology team as well as NTU undergraduate students Frazer, Chloe, Sara and Ghazelle, who worked really hard and were brilliant through a long day, assisted by mini-microbiologists Holly from South Wolds Academy and Bethany from Crossdale Drive primary school.
Congratulations to AROM PhD students Eden Mannix-Fisher, Samuel Dawson, Rachel Whelan and Stephen Thompson. Not only have they had their abstracts accepted for presentation at the Microbiology Society Annual Conference 2020 in April, but they have also all been awarded Microbiology Society Conference Grants towards travel. In addition, Samuel Dawson and Frazer McCuaig (MBiol placement student) have had their work accepted for presentation at the Society for Applied Microbiology’s Early Career Scientist Research Symposium in March. Acceptance of their abstracts for poster presentations comes with grants to cover registration and transport costs.
Well done all! It’s great to see your hard work being recognized by national learned societies. Staff and students from the AROM team visited Nottingham Free School this week to deliver outreach sessions to four groups of year 10 pupils. Dr Jonathan Thomas showed pupils the Nanopore MinION – a USB-stick-sized DNA sequencer – and explained how next-generation sequencing technologies and epidemiology are being used to understand and control infectious diseases, including those caused by antibiotic-resistant bacteria and the current novel coronavirus outbreak. Dr Jody Winter made a case for the roles of microbes in “saving the world”, including their potential applications in environmentally friendly food and biofuel production, and degradation of plastics. And our MBiol students Frazer McCuaig and Simon Barratt were on hand to answer pupils’ questions about university life – thank you for volunteering!
The EU-funded exposome research project ATHLETE – Advancing Tools for Human Early Lifecourse Exposome Research and Translation – launched this week with a kick-off meeting in Barcelona. ATHLETE is a consortium of 22 partners from 11 European countries and the United States.
The project aims to study the effects of many environmental hazards on human health from preconception to adolescence. The final goal of the project is to develop a toolbox that can be used to evaluate the effects of a large group of environmental exposures in individuals as well as in communities in order to design policies and interventions to prevent exposures and to reduce health impacts. The exposome concept implies a shift of perspective in the research of how environmental hazards affect human health. Instead of looking at the consequences that each exposure could have on a living system, the exposome takes into account all the exposures an individual is subjected to from conception to death. The exposome takes into account all those elements we are exposed to via our diet, lifestyle and the environment we live and work in, as well as internal biological factors such as metabolism, gut microbiota, inflammation and oxidative stress. Dr Lesley Hoyles of the AROM research group will lead the microbiome part of this ambitious project, processing samples and analysing shotgun metagenomic data derived from over 1000 children enrolled in the study. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 874583. This post reflects only the author's view and the European Commission cannot be held responsible for any use that may be made of the information it contains.) Seven of our staff and students have had abstracts accepted for presentation (6 posters and 1 talk) at the Microbiology Society Annual Conference 2020, which will be held in Edinburgh in April. We're especially delighted that some of our PhD students will be presenting at a major conference for the first time. Congratulations to all!
Special congratulations to undergraduate student Frazer McCuaig (MBiol Microbiology) who started a 10-month NTU-funded research placement with us in September 2019. His successes in the lab during the first few months of his placement meant he was able to submit a first-author abstract to this conference before Christmas. |