1st April 2022
BACTOBIO AWARDED PRESTIGIOUS BIOMEDICAL CATALYST GRANT TO HELP FIGHT ANTIMICROBIAL RESISTANCE
Bactobio has been awarded £416,000 in a prestigious Biomedical Catalyst award from Innovate UK, the UK’s innovation agency. This is the largest of the four grants we have been awarded by IUK and brings our total non-dilutive funding to £1.1 million. The Biomedical Catalyst (BMC) was established in 2012 with 3 key objectives:
deliver growth to the UK life sciences sector
deliver innovative life sciences products and services into healthcare more quickly and effectively
provide support to academically and commercially led research and development
This 21-month project will support us in targeting the growing threat of antimicrobial resistance (AMR), aiming to discover promising novel pre-clinical compounds against the WHO critical pathogen Pseudomonas aeruginosa. In this post, we highlight the scale of the growing AMR crisis and outline how Bactobio aims to use this project to help revitalise the pipeline of new antibiotics in development. The antimicrobial resistance crisis Antimicrobial resistance (AMR) is recognized by the UN and WHO as a critical systemic risk to modern healthcare. Over time, bacterial pathogens have developed resistance to current antibiotics which can leave them impossible to treat with current therapies. Already more than 1 million people die every year from infections that cannot be cured with available antibiotic treatments and that number is rising. An estimated 10 million people will die as a result of AMR by 2050 unless significant action is taken, making these infections humanity's biggest killer (Figure 1).
Figure 1: Deaths attributable to AMR every year compared to other major causes of death.
Pseudomonas aeruginosa: a priority pathogen
P. aeruginosa is a bacterial pathogen ranked among the most critical threats for spreading AMR. Today, respiratory infections with P. aeruginosa are a leading cause of morbidity and mortality in people with cystic fibrosis and the most frequent hospital-acquired infection among UK critical patients. Worldwide there are more than 300,000 infections each year and 15,000 within the UK alone. Infection rates have been exacerbated by the COVID-19 pandemic, with an estimated one in two ventilator patients infected.
Within AMR, P. aeruginosa is a particular pathogen of concern due to its extensive intrinsic, adaptive and acquired resistance mechanisms against most known drugs (Figure 2). Through intrinsic mechanisms, the pathogen is able to prevent entry of or throw out certain drugs. With adaptive mechanisms, bacteria can change their physical growth properties to escape killing, such as by moving away from areas of high antibiotic concentration. In acquired mechanisms, bacteria take up the genetic code for resistance mechanisms from other surrounding microbes. Current extended drug regimens required to treat these infections are associated with severe side effects and can accelerate the build-up of resistance within and between patients.
Figure 2: Mechanisms of antibiotic resistance in P. aeruginosa Potential solutions from the soil
Being able to treat bacterial infections in the future requires action now to discover new therapies and protect those already in use.
80% of antibiotics used today were isolated from the ~1% of soil bacteria which could be cultured in the laboratory. This bioresource has now been exhausted, with no new bacterially-derived antibiotics launched since the 1980s and synthetic discovery efforts failing to fill the void. Development of new antibiotics over recent decades has proven expensive and inefficient, costing more than $1 billion to develop a new drug.
While synthetic discovery strategies have as yet failed to fill the antibiotic gap, bacteria have evolved over three billion years to produce compounds with the ability to kill competing species with high efficacy and specificity. The remaining 99% of previously unculturable soil bacteria therefore represent a valuable untapped source of new antimicrobials. By mining these bacteria for new solutions, Bactobio has the potential to make a real impact for the millions of patients impacted by AMR each year.
Bactobio’s Biomedical Catalyst project
In this project, Bactobio aims to search for new antibiotics against P. aeruginosa from our growing library of previously unculturable soil bacteria.
The project comprises five technical work packages, starting with the implementation of new technology to increase the diversity of our captured novel bacteria and ending with the discovery of novel antimicrobial compounds.
In the first stage, we will continue to isolate novel bacteria and improve our machine learning to exploit these bacteria to their full potential. With this, we hope to increase our ability to annotate novel biosynthetic gene clusters (areas of the genome associated with production of valuable secondary metabolites), which we use to guide our screening strategies. Following screening, active hits will be isolated, identified and characterised. Hit compounds will then be tested against our library of clinically relevant strains and for toxicity.
We have set an ambitious goal to find 5 – 10 promising pre-clinical antibiotic compounds during this project, providing a compelling case for further drug development. Outputs would provide real hope to over 35,000 cystic fibrosis patients worldwide who are chronically or intermittently infected with P. aeruginosa and reduce pressure on critical-care wards worldwide.
Bactobio has developed a platform to culture the 99% of soil bacteria that have previously not been culturable in the laboratory and uncover valuable secondary metabolites they produce. Our proprietary technology combines microbiology with bioinformatics and machine learning to iteratively expand our access to novel species with the potential to produce novel solutions across healthcare, agriculture and industrials markets: our first target is the growing antibiotic resistance crisis.