Oceania

Foodborne illness affected 1 in 10 people globally in 2010, causing over 400,000 deaths. Bacteria have a substantial contribution to this burden.  We’ve known for decades what some of the most dangerous bacterial species are and the potentially devastating effects they can have on health, but what has been less well understood is how and where these bacteria get into, persist and evolve in an increasingly globalised food system, nor what other bacterial pathogens are causing disease but for which we haven’t had the tools to detect. Not only do these knowledge gaps make it difficult to develop interventions that will reduce foodborne illness, but that there is an increasing challenge to understand how massive global drivers, such as climate change, technology innovation, or other geopolitical events can alter the profile of bacteria within the food system. We have good information on how economies and environments shift due to global pressures, but less so on how microbial ecologies likewise shift.  How do these change the enduring hazards we’re aware of? And how will these lead to new, emerging hazards? This is partly due to an historic tendency to focus on individual bacterial species known to pose risks to health. But bacteria live more complex lives; they exist in interacting communities of microbes, which can rapidly evolve to exploit new ecological niches. In a new review, authors from the Quadram Institute, the University of East Anglia, the Royal Veterinary College and Massey University are calling for more holistic approaches that assess the risks and monitor changes in these microbial communities as a whole, and across the food chain. With the rapid development of genomic technologies, we are now in a better position than ever to do that. Whole genome sequencing and metagenomics provide the tools to sequence the genomes of every organism in a sample. Metagenomics gives a full picture of what’s present in a particular environment, and through sequencing the whole genome of a bacterium, you can identify the genetic elements that give those microbes the edge to exploit a particular niche, such as tolerance of antimicrobials. That genetic fingerprinting can also help identify the sources of outbreaks, linking genetically identical strains of bacteria that might be indistinguishable otherwise. It can also be used to trace back when and how particularly problematic bacterial strains emerged – something that becomes increasingly challenging but ever more important as global food chains become more complex. For example, whole genome sequencing tracked the ‘microevolution’ of the most prevalent Salmonella Typhimurium strain globally. This strain not only acquired antimicrobial resistance genes but also genes conferring tolerance to heavy metals, most probably through exposure to zinc and copper used as supplements in pig feed. It has also picked up viral genes that aid its invasion of host cells, all of which turned this strain from the cause of an emerging epidemic in animals to an enduring threat that’s spread across the world. The prevention and control of Campylobacter, another globally important foodborne pathogen, has also benefited from the application of genome sequencing tools. These tools have provided powerful approaches to tracking and tracing the transmission of this bacteria through the food chain, as well as identifying and determining the source of outbreaks. This is why the researchers want to see genomic surveillance adopted much more widely, across the world, so we can help keep ahead of the microbial threats as they emerge. “What will be key to these surveillance systems is not only sensitivity, but also timeliness, so that pre-emptive action to prevent foodborne illness can be taken rather than using the information to respond to incidents once they have occurred” said Professor Alison Mather from the Quadram Institute. The call goes out to governments and international agencies to dedicate resources to genome-based surveillance, so that its benefits can be felt equitably. Currently, most genomic surveillance is based in well resourced areas. But these are truly global problems and if we are to make our food supply chain resilient to future shocks, it needs a truly global response. The economic and social benefits of global genomic surveillance of the food system are there for us all. As we get more and more genomic and metagenomic data, from a wider and more diverse set of sources, the better surveillance can pick up threats. Accordingly, the review summarises perspectives shared by food producers and other food businesses as they begin their own pursuits of using genomic technologies to help safeguard consumers. Informed by prioritisation exercises and proof-of-concept research projects, including those in the UK’s Food Safety Research Network, Dr Matthew Gilmour notes that “businesses understand there is a great depth of information that can be provided by genomics, and thankfully, we can pair that technological promise with meaningful new solutions to help control food safety risks”. Scientists, governments and businesses are now building a 21st century system to better prevent, detect and respond to the microbial threats that travel the world on our food. To enable the adoption of genomic-based systems, the costs of the technology that underpins genomics are dropping, the community working in this area is dedicated to equitable data-sharing and through knowledge exchange, and access to training genomics at this level is becoming more and more accessible. Reference: Foodborne bacterial pathogens: genome-based approaches for enduring and emerging threats in a complex and changing world, Alison E. Mather, Matthew W. Gilmour, Stuart W.J. Reid, Nigel P. French Nature Reviews Microbiology doi: 10.1038/s41579-024-01051-z

Quadram Institute scientist Dr Alison Mather has been granted two prestigious international partnership awards to build collaborations with researchers in New Zealand and The Netherlands. The Biotechnology and Biological Sciences Research Council (BBSRC) funded four-year programmes, which fall within their Global Highlight area of fostering a One Health approach to diseases of zoonotic origin. These awards will involve activities such as the exchange visits of scientists (initially online), development of collaborative research programmes, a seminar series to widen exposure of the science and research, and workshops to consolidate plans for future research proposals and wider impact. The partnership with One Health Aotearoa (OHA), an alliance of over 100 infectious disease researchers from multiple organisations across New Zealand, provides a unique opportunity to share complementary skills and expertise in the genomic epidemiology and control of zoonotic pathogens of common interest to both NZ and the UK. The award will facilitate the exchange of knowledge and training in areas of food safety, phylodynamic modelling, and cutting-edge sequencing and metagenomics. Professors David Murdoch (University of Otago) and Nigel French (Massey University), co-Directors of One Health Aotearoa said “This is an exciting opportunity to further develop our collaboration with Dr Mather and her colleagues at the Quadram Institute. One Health Aotearoa is committed to reducing the impact of zoonotic pathogens and antimicrobial resistance through the application of new tools and techniques that enable us to understand how pathogens emerge and are transmitted between animals and humans. There has never been a more important time to develop international partnerships dedicated to working on these issues, and we are delighted to be part of this initiative” The second partnership is with Utrecht University in The Netherlands and home of the WHO-Collaborating Center for Campylobacter and Antimicrobial Resistance from a One Health Perspective and the OIE-Reference Laboratory for Campylobacteriosis. This collaboration will allow the development of advanced genomic and metagenomic approaches to understanding Campylobacter, the primary bacterial cause of foodborne illness in Europe, and provide a platform to exchange skills in machine learning, phylogenetics and sequencing. Dr Aldert Zomer said: “Infectious diseases cause social, economic and public health problems, and growing antimicrobial resistance threatens to make diseases untreatable. A partnership with the Quadram Institute supports the WHO Collaborating Centre for Campylobacter mission to develop new techniques and improved tools for Campylobacter isolation, identification and typing, and antimicrobial resistance which can be used to support surveillance, attribution and intervention studies” These awards will facilitate long term collaborations, establishing networks of individuals with synergistic skills and common aims, encouraging the sharing of experiences and practices working across disciplines, sectors and stakeholders to strengthen One Health research initiatives in the UK and in the partner countries. Dr Mather and her research group at the Quadram Institute on the Norwich Research Park work to understand the relative contributions of animals, humans, the environment and food to diseases caused by pathogenic bacteria and antimicrobial resistance. Dr Alison Mather said: “I am delighted to have these opportunities to develop stronger links with scientists in both New Zealand and The Netherlands. The One Health approach is key to understanding the sources and drivers of the threats posed to society by bacterial pathogens and antimicrobial resistance. Sharing techniques and knowledge with experts in other countries will not only add value to our own respective projects, but also generate new ideas on how to tackle these global problems.”

Professor Cynthia Whitchurch’s team from the Quadram Institute and the ithree institute at the University of Technology Sydney, showed that P. aeruginosa has all of the necessary proteins for natural transformation and can actively acquire and incorporate DNA from the environment whilst in biofilms. This represents a paradigm shift in our understanding of these bacteria which are of a major concern because of the number of strains emerging worldwide that are resistant to multiple different antimicrobials. Understanding how they acquire genes for resistance is critical to controlling and preventing the growing problem of antimicrobial resistance (AMR). Apart from inheriting it when a parent cell divides, bacteria can acquire genetic material in several ways. This has implications for understanding how genes for AMR spread and how resistant strains evolve. Bacterial horizontal gene transfer is often in the form of conjugation: direct contact between two cells over a period that allows genetic material to pass between them. Another form is transduction, where bacteriophages take up DNA from one cell and inject it into another. The third form of horizontal gene transfer, natural transformation, sees bacteria take up DNA from the environment. This is far from being a passive process. It involves a lot of energy expenditure to put the cell into a “competent” state. Only a small proportion of bacterial species have been found to be competent for natural transformation, and, until now, Pseudomonas aeruginosa was not one of these. But it’s importance in the context of the spread of AMR has warranted a rethink. Pseudomonas aeruginosa is one of the World Health Organisation’s top priority pathogens for which there is a critical need for new antibiotics. Whilst they are not usually a problem for healthy people, they can infect the immune-suppressed, causing a range of infections including pneumonia, bacteremia, chronic wounds, and are also associated with hospital-acquired infections. They survive in different environments, in part helped by an ability to form biofilms. Biofilms are thin surface-associated colonies of bacteria surrounded by a matrix that provides protection from drying out and exposure to toxins, antibiotics and the immune system. An increased resistance to cleaning and disinfectants makes biofilms in hospital environments a hazard, especially on surfaces of medical equipment. Bacteria make the biofilm matrix by extruding out of their cells a slime comprised of sugars, proteins and, as Prof. Whitchurch previously discovered, DNA. This extracellular DNA (eDNA) is a pivotal structural component of the protective biofilms but is also a potential reservoir of genetic material for bacteria to take up. [caption id="attachment_21129" align="alignright" width="417"] P. aeruginosa in a biofilm that have taken up DNA containing a green fluorescent protein gene. Nolan et al., MicrobiologyDOI 10.1099/mic.0.000956[/caption] Pseudomonas aeruginosa produces copious amounts of eDNA in biofilms, and appears proficient at acquiring genetic diversity, which gave the research team reason to question the accepted consensus on how these bacteria do this. Could P. aeruginosa carry out natural transformation under certain conditions? The team looked at the genes used for natural transformation in other bacteria, and scoured the genomes of P. aeruginosa strains. Each had a full set of matching genes, including those for making a pilus structure and for translocating DNA, suggesting natural transformation was possible in P. aeruginosa. In a series of experiments detailed in the journal Microbiology, the team demonstrated that P. aeruginosa could carry out natural transformation when in the conditions found in a biofilm. Using marker genes and strains that could not undergo other forms of horizontal gene transfer, they showed that the P. aeruginosa in biofilms could, for example, take up DNA containing a fluorescence gene, making bacteria that fluoresce. In other experiments, P. aeruginosa in biofilms growing on agar plates or in liquid could take up resistance genes, enabling them to grow in the presence of an antibiotic. “The finding that P. aeruginosa is capable of natural transformation is a paradigm shift in our understanding of how this pathogen acquires genetic diversity” commented Prof. Whitchurch. “Natural transformation may be an important mechanism for the acquisition of antibiotic resistance and virulence genes and a significant contributor to the rapid increase in the number of multidrug-resistant P. aeruginosa strains that are an emerging problem worldwide.” Reference: Pseudomonas aeruginosa is capable of natural transformation in biofilms Laura M. Nolan , Lynne Turnbull​, Marilyn Katrib, Sarah R. Osvath​, Davide Losa​, James J. Lazenby​, Cynthia B. Whitchurch, Microbiology DOI: 10.1099/mic.0.000956

Despite continued history as one of the major water-related diseases, much is still unknown about the biology of the bacterial agent of typhoid fever, Salmonella enterica ssp. enterica serovar Typhi (S. Typhi), particularly in relation to factors governing its persistence and fate in the environment. This pathogen is still a major source of infectious disease illness and death, causing an estimated 11.0 –17.8 million illnesses annually and 117,000 deaths in 2017. In recognition of this gap in knowledge and its importance in potentially guiding interventions to halt transmission, the Bill and Melinda Gates Foundation launched a new Global Grand Challenge Exploration (GCE) to examine the environmental niches of S. Typhi. [caption id="attachment_19965" align="alignright" width="277"] Loo with a view - a toilet located in a water catchment in Fiji[/caption] Building upon existing field programs of research in Fiji and Madagascar, Dr Aaron Jenkins (University of Sydney/Edith Cowan University, Australia), Dr Gemma Langridge (Quadram Institute Bioscience, UK) and Professor France Daigle (Université de Montréal, Canada) formed a consortium to tackle separate aspects of this challenge. This group of researchers received three GCE grants totalling USD 300,000 over the next 18 months to study the survival of S. Typhi in the context of soil and water microbiomes, within other organisms and how the structure of the genome changes to facilitate environmental persistence. Quadram Institute Bioscience, UK, led project: One challenge to working with S. Typhi is that is cannot be cultured from water. This hampers efforts to quantify the bacterial burden in this key environment and prevent its onward transmission to humans. S. Typhi is known to undergo structural genome rearrangements that can reduce growth rate and are probably selected for as an environmental adaptation towards survival in water. Dr Gemma Langridge and Dr Alison Mather will investigate the impact of these genome rearrangements on S. Typhi survival in water from high and low endemic regions in Fiji. As well as providing a better understanding of this adaptation, this project also has the potential to enable resuscitation of S. Typhi from water that will improve the monitoring of control measures. University of Sydney/Edith Cowan University, Australia, led project: The University of Sydney/Edith Cowan university grant deals specifically with describing the nested micro-ecology of sediment associated biofilms in high typhoid incidence hydrological networks. Building from work conducted during his PhD at Edith Cowan University, Dr Jenkins postulates that sediment associated biofilms are an important ecological niche for S. Typhi survival in high typhoid incidence hydrological networks, and its transport and fate within these systems is highly influenced by its association with sediment. Persistence in these environments and subsequent viability for human infection is determined by biofilm community composition (relationships with inorganic particles, other bacteria, algae and fungi and micro-grazing protozoa and metazoa), diversity, and physical structure along with the bioavailability of dissolved organic matter (DOM) and nutrients. This investigation will use cutting-edge genomics and biophysical environmental measures to screen for S. Typhi while simultaneously defining the micro-ecology of a broad suite of sediment associated biofilms from high typhoid incidence hydrological networks in Fiji. This research will determine the relationships between biofilms, sediment in river benthos and water column, their S. Typhi load, and functionally important trophic elements of riverine systems, namely the rhizome of aquatic plants, bottom dwelling fishes, crustaceans and bivalve molluscs. Université de Montréal, Canada, led project: Professor France Daigle hypothesizes that members of the water microbial community interact with S. Typhi and promote persistence by providing nutrients and a favourable environmental niche. These interactions may lead to an environmental reservoir for S. Typhi and may increase its transmission to humans. This project will identify microbial partners in the water ecosystem and determine the mechanisms that enable S. Typhi persistence in the aquatic environment by using microcosms as a simple reproducible environmental representative system to determine and compare S. Typhi persistence within a mixed but defined microbial community. The project will determine which microorganisms increase S. Typhi fitness and the persistence strategy. The presence of specific microbes that were shown to be beneficial for S. Typhi in microcosms will be determined by analyses of water samples from an endemic region of typhoid fever. Quadram Institute researchers are also involved in two further grants from this Global Grand Challenge Exploration: S. Typhi and Protozoa in Contaminated Water in Zimbabwe - Prof. Rob Kingsley Investigating persistence of S. Typhi in the aquatic environment in Madagascar, led by Prof. France Daigle, Université de Montréal. QI: Dr Gemma Langridge and Prof. John Wain.

Quadram Institute Bioscience and the University of Newcastle, Australia have signed a Memorandum of Understanding to promote cooperation and a stronger relationship between the two organisations. Quadram Institute Bioscience (QIB), a partner on the Norwich Research Park and the University of Newcastle, a research-intensive university ranked in the Top 10 in Australia, are centres of excellence in the promotion of health and the prevention of disease. [caption id="attachment_18085" align="alignright" width="320"] Professor Kevin Hall, Senior Deputy Vice-Chancellor, the University of Newcastle, Australia and Professor Ian Charles, Director of the Quadram Institute[/caption] QIB and the University of Newcastle share many scientific interests and have complementary research strengths in bioscience, health sciences, immunology and the microbiome. The Memorandum of Understanding cements a desire on both parts to build closer links between the two centres by exploiting synergies in these strengths. This will maximise the impact of both centres’ research in the areas of food security, food safety, gut health and understanding the microbiome. The MOU will also broaden training opportunities for postgraduate students and early career researchers. It will facilitate student exchanges and co-supervision. A workshop is planned, hosted by the Quadram Institute to bring together key researchers from the University of Newcastle to meet QIB colleagues and spark collaboration on projects of mutual interest. The MOU was signed by QI Director Professor Ian Charles and Professor Kevin Hall, Senior Deputy Vice-Chancellor and Vice President Global Engagement and Partnerships at the University of Newcastle, Australia. Professor Hall visited the Quadram Institute on 21st March and met a number of key QIB scientists. “The University of Newcastle is committed to research excellence that impacts communities throughout Australia and across the globe. We are proud to be partnering with Quadram Institute Bioscience and combining our aligned research strengths in in bioscience, health sciences, immunology to work on addressing the global food and health challenges. This new collaboration holds great promise and we look forward to witnessing how this partnership can push the boundaries of innovation and discovery,” Professor Hall said. “This agreement will enable exciting world-class research and I look forward to seeing new projects come to fruition over the next few years. Our ambition is to establish the Quadram Institute as a recognised world leader in research into food, health, microbiology and gut health. World-class science relies on working collaboratively with the very best research centres across the globe which is why I’m delighted to sign this agreement” said Professor Charles.

“Last year Professor John Wain and I gave training in Fiji which enabled Fijian scientists and staff to identify the microbe responsible for an outbreak in a neonatal unit of a hospital. At the Quadram Institute we have a strong collaboration with Fiji National University (FNU) working on water-related diseases caused by microbes such as Salmonella. As part of our ongoing collaboration, John Wain and I headed to Fiji last August to give four days training on DNA sequencing. Our trip built on our previous interactions in Dr Gemma Langridge’s group with FNU, funded by the Bill & Melinda Gates Foundation, including work we have done giving training remotely through online videos and sharing methods of how we sequence DNA. The week before we arrived in Fiji, FNU had opened a new containment lab built for virology. The lab is made of two shipping containers and has a collection window for people to hand in samples. Inside the containment lab, there is state of the art equipment including Oxford Nanopore’s MinION which allows rapid sequencing of samples. John and I went to the lab in Suva, Fiji to share our knowledge of sequencing the DNA of viruses and microbes using MinION. Our training course covered all steps including preparation of extracted DNA for library prep, laptop and MinION set up, sequencing, basecalling and standard data analysis. The people we were training came from a variety of backgrounds. There was a master’s student, a nurse, a lecturer from the university and staff running the new containment lab. There was also an ecologist interested in soil microbiomes and viruses. Some people were interested in bacteria, some people were looking more at metagenomics, while some were planning to sequence viruses. It was a real mix. Our expertise in the Langridge group is on sequencing bacteria, so we initially developed the training using protocols for bacteria. The good thing about sequencing using nanopore sequencing is that you can use it for sequencing different organisms. But for each organism, there are slightly different methods that are used. We were flexible with our training, and we highlighted other protocols that could be used on other types of samples at each step. Towards the end of the training, we covered data analysis. Depending on what your sample is, your data analysis could be very different. We suggested ideas of the different ways you could use the data whether putting it into a pathogen identification tool or looking for antimicrobial resistance genes. One of the aspects of the training that I enjoyed most was adapting the course as it progressed, to each of the people taking part and their different areas of interest. I enjoyed visiting Fiji as a country too. It’s the first time I’ve ever been to the southern hemisphere and to the other side of the world. It took us three days of travelling to get there. The scenery of tropical forest and endless ocean was stunning though negative impacts of the colonial period on Fijian communities were apparent in places, including the lack of infrastructure and poverty. While we were in Fiji, there was an outbreak in the neonatal department of the local hospital. The scientists and staff we trained used their new skills to perform the first outbreak sequencing in Fiji. They found that the outbreak was caused by the bacteria Acinetobacter baumannii and that it was resistant to the antibiotic carbapenem. Often short-read sequencing is used which is very good at showing you small changes in DNA called single nucleotide polymorphisms (SNPs), which can be important for monitoring resistance or changes in pathogenicity. In this case, the Fijian researchers used long-read sequencing which gives even more information and allows you to see genome rearrangements. Understanding genome rearrangements is something we study in the Langridge lab. We know that these rearrangements can make a microbe go into a kind of dormant stage, so it won’t necessarily show up as an active infection, but it could be lying dormant and still be infecting others. The week after we left, our Fijian colleagues adapted one of the protocols we used on the training course to do long-read sequencing of these outbreak isolates. They sequenced the two outbreak samples from the hospital, and a couple of Salmonella Typhi and E. coli samples so they could compare them. They got complete genome assemblies, which was amazing for a first sequencing run. Within two weeks those we trained went from having the equipment, to using it, to responding to a public health situation independently. In the future we hope to continue our collaboration and support capacity building of sequencing in Fiji by running a more in-depth data analysis session covering bioinformatics, either in person or online. The trip was only possible thanks to funding from the JIDCuk Charitable Trust which supports scientific research and scientists in developing countries through funding training courses and postgraduate projects for students registered at institutions in developing countries. Members of the Langridge lab will be running another training course this year, this time at the National Animal Health Research Centre (NAHRC) in Nepal. We will help our colleagues establish a MinION sequencing facility to aid monitoring of antibiotic resistance in pathogens isolated from food animals.