Periodic Reporting for period 1 - PEST-BIN (Pioneering Strategies Against Bacterial Infections)
Periodo di rendicontazione: 2021-01-01 al 2022-12-31
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.
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.
In WP1, ESRSs have jointly made significant progress towards deliverables 1.1-3. In terms of infection biomarker delivery, we have new proteomics datasets for Streptococcus pneumoniae, Staphylococcus aureus and Listeria monocytogenes, with further studies underway. Validation of the biomarkers in true clinical patient samples has commenced, as well as studies on consolidating diagnostic markers based on integration of consortium-wide omics data. ESR2 has delivered impressive results in terms of optimizing production of graphene sensors with the desired technical characteristics and ESR3 has successfully developed a methodology for synthesis and design of triazole receptors for identified biomarkers. We have met the requirements for deliverable 1.1 are are well under way to reach deliverables 1.2. and 1.3.
In WP2, ESR7 developed an air liquid interface (ALI) model for studying S. aureus infections on a layer of differentiated human cells that closely resembles lung surface. ESR 8 probed the phosphoproteome of S. pneumoniae, focusing specifically on regulatory events in cell division and chromosome segregation of the pathogen. ESR 9 developed and implemented a pipeline for proteogenomics and phosphoproteomics analysis of E. coli and K. pneumoniae. ESR 12 focussed on biofilm development of pathogenic E. coli, using proteomics and genomic phylostratigraphy to identify relevant targets for drug design. ESR 11 conducted a large scale screening of >1000 pathogenic strains in clinical environment, conducting genomics analyses. Finally, ESR 10 developed a machine learning approach for predicting phenotypes by ultra-high resolution microbiomics. Deliverable 2.1. is essentially already achieved (not yet reported), deliverables 2.2 and 2.3 are well under way and we expect delivery on time.
In WP3, ESR13 has made significant progress in production of “green” nanoparticles with antibacterial properties, and their functionalization. ESR14 has made equally good progress in fabrication of graphene-polymer composites with antibacterial properties, progressing towards deliverable 3.2 (also on schedule). Materials provided by ESRs 13 & 14 will be integrated with antimicrobial peptides from the NAICONS discovery pipeline, provided by ESR15. ESR 15 has so far identified 39 active fractions from environmental isolates, that are currently being characterized as potential new antibacterial compounds. Hence, the work on Deliverable 3.3 is also on schedule and we expect delivery on time.
Secondments, network wide and local training activities are progressing as expected, as well as the outreach activities.
In WP2, ESR7 developed an air liquid interface (ALI) model for studying S. aureus infections on a layer of differentiated human cells that closely resembles lung surface. ESR 8 probed the phosphoproteome of S. pneumoniae, focusing specifically on regulatory events in cell division and chromosome segregation of the pathogen. ESR 9 developed and implemented a pipeline for proteogenomics and phosphoproteomics analysis of E. coli and K. pneumoniae. ESR 12 focussed on biofilm development of pathogenic E. coli, using proteomics and genomic phylostratigraphy to identify relevant targets for drug design. ESR 11 conducted a large scale screening of >1000 pathogenic strains in clinical environment, conducting genomics analyses. Finally, ESR 10 developed a machine learning approach for predicting phenotypes by ultra-high resolution microbiomics. Deliverable 2.1. is essentially already achieved (not yet reported), deliverables 2.2 and 2.3 are well under way and we expect delivery on time.
In WP3, ESR13 has made significant progress in production of “green” nanoparticles with antibacterial properties, and their functionalization. ESR14 has made equally good progress in fabrication of graphene-polymer composites with antibacterial properties, progressing towards deliverable 3.2 (also on schedule). Materials provided by ESRs 13 & 14 will be integrated with antimicrobial peptides from the NAICONS discovery pipeline, provided by ESR15. ESR 15 has so far identified 39 active fractions from environmental isolates, that are currently being characterized as potential new antibacterial compounds. Hence, the work on Deliverable 3.3 is also on schedule and we expect delivery on time.
Secondments, network wide and local training activities are progressing as expected, as well as the outreach activities.
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 will be used as “plug-and-play” disposable chips via a flash-memory micro-SD jack, so no heavy machinery for readouts will be required. Therefore, their environmental footprint will be close to zero. So far, we have identified the markers needed for detection of several important pathogens, and we made strong progress in terms of chip design and receptor synthesis. We expect to deliver this technology as promised by the end of the project.
Regarding the understanding of mechanisms of infection, and identification of possible new drug targets, PEST-BIN is systematically redefining how such studies should be performed, and 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 comes in terms of data analysis, where we integrate many datasets and look for emergent properties during the dynamic infection process.
In terms of killing infectious biofilms, PEST-BIN strategy is to unite one of EU leaders in developing new antibiotics – Naicons, with the development of antibacterial properties of graphene. We have engineered hydrogel coatings and "green" nanoparticles integrated with antibacterial graphene coatings, which will in turn be loaded with antibiotics from Naicons. We hope that such a molecular “nano-weapon” will be able to physically penetrate deep into bacterial biofilms, where it will ensure steady and sustained release of antibiotics in the otherwise protected heart of the biofilm.
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.
Regarding the understanding of mechanisms of infection, and identification of possible new drug targets, PEST-BIN is systematically redefining how such studies should be performed, and 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 comes in terms of data analysis, where we integrate many datasets and look for emergent properties during the dynamic infection process.
In terms of killing infectious biofilms, PEST-BIN strategy is to unite one of EU leaders in developing new antibiotics – Naicons, with the development of antibacterial properties of graphene. We have engineered hydrogel coatings and "green" nanoparticles integrated with antibacterial graphene coatings, which will in turn be loaded with antibiotics from Naicons. We hope that such a molecular “nano-weapon” will be able to physically penetrate deep into bacterial biofilms, where it will ensure steady and sustained release of antibiotics in the otherwise protected heart of the biofilm.
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.