Pioneering Strategies Against Bacterial Infections

Project Information

PEST-BIN

Grant agreement ID: 955626

DOI

10.3030/955626

Project closed

EC signature date 28 August 2020

Start date 1 January 2021

End date 31 December 2024

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 4 144 986,00

EU contribution

€ 4 144 986,00

Coordinated by

DANMARKS TEKNISKE UNIVERSITET
Denmark

Periodic Reporting for period 2 - PEST-BIN (Pioneering Strategies Against Bacterial Infections)

Reporting period: 2023-01-01 to 2024-12-31

Summary of the context and overall objectives of the project

The World Health Organisation (WHO) classified antibiotic resistance as one of the greatest threats to global health. Due to misuse and excessive consumption of antibiotics, anti-microbial resistance (AMR) in bacteria has expanded world-wide and is increasing at accelerating rates. Discovery of new antibiotics is not likely to turn the tide. The humanity clearly needs to pioneer new disruptive technologies to re-gain the upper hand in fighting bacterial infections. To address this issue, PEST-BIN is targeting three areas of science and technology development, corresponding to three scientific work packages in the project:

1) Diagnostics: Development of reliable, rapid, sustainable and cost-effective analytical techniques for comprehensive diagnostics and characterizations of infectious bacteria.
2) Infection mechanisms: Generation of proteomics datasets that are relevant, comprehensive and time-resolved from the perspective of infections and the use of a wide array of computational tools to extract relevant information about mechanism of infection from proteomics datasets.
3) Destroying bacterial biofilms: A new line of attack on biofilms: mobilizing players from two distant fields: nano-engineering of antibacterial surfaces and development of new antibiotics that can be conjugated with such surfaces for enhanced delivery to biofilms.

Scientific advances are of course only one component of what PEST-BIN aims to deliver. Our other contributions are in training and enabling ESRs to become future leaders in this field, and strengthening the European capacity for interdisciplinary collaboration.

Overarching strategic objectives of PEST-BIN are:
1) Develop the methods and the knowledge base for accelerated pioneering and implementation of innovative solutions for diagnosing and fighting bacterial infections.
2) Train a cohort of interdisciplinary experts who can effectively address challenges related to bacterial infections, working at the interface between academia and other sectors (industry, hospitals, public institutes).
3) Strengthen the European network of universities, companies, hospitals and institutes working on bacterial infections, to provide a dynamic platform for future training of ESRs.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In WP1, ESRSs have achieved all scientific deliverables 1.1-3. In terms of infection biomarker delivery, we have publications of biomarkers for Streptococcus pneumoniae, Staphylococcus aureus and Listeria monocytogenes. The BacSPaD database has been constructed with a broad overview of genomes of sequenced pathogens. And finally, sensor design and construction have been successfully completed, connecting the discovery part of the project to impactful sensor implementation. IP rights around PEST-BIN sensors have been protects, and based on that a startup company LayerLogis has been launched. Our ESRs have successfully demonstrated that interdisciplinary approaches can lead to rapid advancements in science and innovation when it comes to infection diagnostics.

In WP2, ESRs have completed all scientific deliverables 2.1-3. In this WP, our ESRs have tackled some fundamental questions about mechanisms of infection, striving to understand how pathogens function and what makes some of them particularly dangerous. This results in a considerable body of new knowledge. In particular, new mechanistic insights were delivered in terms of understanding proteome dynamics, regulation of cell division, and functioning of pathogens in clinical environments. Computational approaches were developed to leverage machine learning/AI to address fundamental questions about pathogen adaptability and evolution. Important methodology advances were also delivered in MS proteomics, facilitating further studies of bacterial pathogens. Collaborative environment established by our ESRs was critical in delivering these scientific breakthroughs.

In WP3, ESRs have also achieved all scientific deliverables 3.1-3. Our ESRs successfully combined distant scientific concepts from material science and microbiology, to deliver innovative strategies for eradicating bacterial biofilms. This resulted in development of efficient antibacterial formulation based on advanced nanomaterials and nanomaterial-polymer composites. These were developed alongside the discovery of new antibacterial molecules, spearheaded by Naicons. WP3 ESRs extensively networked with other WPs to test their formulation against relevant pathogens, targeting their weak points that we discovered on our way. Our strategy of combining physical (nanomaterials) and chemical (antimicrobial drugs) killing showed to be particularly effective in reducing the change of emergence of bacterial resistance. With the rising resistance against classical antibiotics, novel approaches such as the ones we developed in PEST-BIN are the best strategy we have to stay ahead in the race against multiresitant microbes.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In terms of infection diagnostics, PEST-BIN is going beyond state-of-the-art by functionalizing graphene-based sensors with receptors specifically designed to capture biomarkers from the bacterial surface that we have detect by "surface shaving" proteomics. Our detection kits will be developed as miniaturized chips, containing basically carbon (graphene) and biodegradable polymers (no gold electrodes or any heavy metals). They can be used as “plug-and-play” disposable chips via a flash-memory micro-SD jack, so no heavy machinery for readouts is required. Therefore, their environmental footprint is close to zero. We have identified the key biomarkers needed for detection of several important pathogens, and accomplished the key milestones of chip design and receptor synthesis. We delivered the promised technology, protected the IP rights, and actually started producing the diagnostic chips in the PEST-BIN spin out LayerLogic AB.

Regarding the understanding of mechanisms of infection, and identification of possible new drug targets, PEST-BIN has delivered new benchmarks on how such studies should be performed, and their results analyzed. In terms of experimental design, we established pipelines for analysis of pathogens' proteome dynamics in contact with human cell lines, in developing biofilms, etc. An even bigger step beyond state of the art came in terms of data analysis, where we integrated many datasets and pin-pointed for emergent properties during the dynamic infection process. Instrumental to this success was the early application of machine learning/AI in data analysis, as well as the use of advanced methods for evolutionary analyses.

In terms of killing infectious biofilms, PEST-BIN strategy relied on leveraging the success one of EU leaders in developing new antibiotics – Naicons, with the development of antibacterial properties of nanomaterials such as graphene and metallic nanoparticles. We have engineered various hydrogel/polymer coatings involving "green" nanoparticles and antibacterial graphene coatings. Such coatings, when loaded with antibacterial molecules from Naicons, become a very effective “nano-weapon” against bacterial biofilms.

Activities pursued within PEST-BIN have allowed some of our beneficiaries to create new alliances and apply for additional research funding together. Overall, PEST-BIN has delivered as promised in terms of strenghtening the European research & innovation environment.

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