A Phenomics Australia and Therapeutic Innovation Australia case study
The challenge: Food poisoning is estimated to affect more than 4 million Australians every year – costing the economy $1.25 billion, and in some cases causing death.
There are an estimated 4.1 million cases of food poisoning in Australia, resulting in 31,920 hospitalizations, 86 deaths, and one million visits to doctors on average every year.
Bacillus cereus is a toxin-producing bacterium and a common cause of food poisoning. This bacterium is an important and neglected human pathogen and is the culprit when it comes to starchy foods like pasta and rice. It multiplies with the food’s nutrients and then releases toxins.
Bacillus cereus releases two types of toxins: one that spreads throughout the food itself and can cause vomiting, and one that’s released within the small intestine after the food is consumed to cause cramps and diarrhea. In some cases, these toxins can have deadly consequences..
The solution: Learning and understanding the toolbox bacteria use to infect us triggering dangerous food poisoning symptoms.
Researchers at The Australian National University (ANU) supported by Phenomics Australia and and TIA’s Pipeline Accelerator scheme, have discovered important details about the many tricks or tools bacteria use to infect us.
Professor Si Ming Man and colleagues study Bacillus cereus, which is responsible for producing toxins that help the bacteria to multiply and cause food poisoning symptoms.
ANU researchers have previously shown that several toxins are implicated in the disease, including the pore-forming toxins hemolysin BL (HBL) and non-hemolytic enterotoxin (NHE). They have shown how the toxins can infect cells, even when the body has fought off others. If one of the tools is lost or neutralized by the immune system, the bacteria have a backup that still allows them to infect and cause disease.
HBL is used to kill cells in the body and establish an infection. The NHE toxin attacks all types of cells in the body by anchoring itself and punching holes in the cell membrane, according to the study published in the journals Nature Microbiology and Nature Communications. NHE is an activator of the NLRP3 inflammasome. Inflammasomes are important for host defense against pathogens. However, individual components of NHE or all combinations of two of the three components did not trigger activation of the NLRP3 inflammasome.
‘“Phenomics Australia provides a world class mouse library which holds the keys to unlocking the secrets of human diseases like food poisoning” Professor Man says. “We are able to access and use unique mouse strains to work out which parts of the immune system fights the toxin. ”
Prevalence of NHE and HBL suggests that both toxins are key virulence factors important for the pathogenesis of Bacillus cereus infection. A better understanding of the host defense strategy against infection will be beneficial and neutralizing toxins might complement current therapies against infection caused by toxin-producing bacteria. “Not every Bacillus cereus produce one or both toxins. Working out which Bacillus cereus produce which toxins will help understand why some bacteria are deadlier than others”. Professor Man says.
The future: Created proteins that can neutralise the activity of the toxins restricting the spread of the infection, and that can be used to complement existing antibiotic regimes.
Antibiotic treatment for food poisoning may become less effective in the future due to bacteria’s growing resistance to antibiotics. Developing new therapeutics against Bacillus cereus, such as using certain drugs that can neutralise the activity of the toxins restricting the spread of the infection, and that can be used to complement existing antibiotic regimes could prove incredibly important when it comes to successful treatment, making this research even more important. Also, and very importantly, similarities between these toxins and their mechanisms of action and others from different bacteria could prove incredibly important when it comes to successful treatment for other very lethal types of bacterial infections.
Scientists smash lethal bacteria that acts like a hammer. https://www.anu.edu.au/news/all-news/scientists-smash-lethal-bacteria-that-acts-like-a-hammer
When Food Kills: Deadly Toxins, Oregon data, and Safety Tips: https://www.corvallisadvocate.com/2022/when-food-kills-deadly-toxins-oregon-data-and-safety-tips/
Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome. https://www.nature.com/articles/s41467-020-14534-3
ANU researchers find new food poisoning toxin. https://www.anu.edu.au/news/all-news/anu-researchers-find-new-food-poisoning-toxin
Researchers boost Bacillus cereus knowledge. https://www.foodsafetynews.com/2020/03/researchers-boost-bacillus-cereus-knowledge/
Bacillus cereus: Epidemiology, Virulence Factors, and Host–Pathogen Interactions. https://www.sciencedirect.com/science/article/abs/pii/S0966842X20302377#!
A multicomponent toxin from Bacillus cereus incites inflammation and shapes host outcome via the NLRP3 inflammasome. https://www.nature.com/articles/s41564-018-0318-0
With an established track record and reputation for excellence, Phenomics Australia Genome Engineering team uses techniques such as CRISPR-mediated mutagenesis, classical gene targeting, and transgenesis to create optimal tools for your research delivering a comprehensive service in genome modification. To meet the high demand for this platform, Phenomics Australia offers genome editing services through four nodes across Australia, operating at Monash, ANU, WEHI, and SAHMRI.
The Therapeutic Innovation Australia (TIA) Consortium is a national network of leading translational research infrastructures across three capabilities – Biologics & Vaccines, Cell & Gene Therapies and Small Molecule Pharmaceuticals. They provide access to expertise and services to assist researchers and SMEs in the development of new therapeutic products.
The Australian Phenomics Facility specialises in the development, characterising and archiving of mouse models of human disease. They have an experienced genomics and bioinformatics capability focussed on the identification of single nucleotide polymorphisms and the phenotyping capability to make the biological associations with probable human disease traits. Their goals are to first derive the underlying genetic mechanisms and then look to extend this across the population and better understand cohort differences and responses. The facility was established in 2005 and receives funding from the Australian Government’s NCRIS, Super Science and CRIS programmes through the Phenomics Australia and contributions from the Australian National University. They have an open access policy and support academic and corporate research programmes in Australia and internationally.