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European Commission Topic
European Commission Topic

Development of a sustainable and multimodal bacterial platform for the treatment of skin and soft tissue infections

The project aims to develop a sustainable and cost-effective multi-modal Zymomonas mobile application for the production of antimicrobial peptides (AMPs) and levan for the treatment of skin and soft tissue infections (SSTIs). To achieve these goals, a highly qualified scientific team will be established, which will promote cooperation between scientific institutions, industry partners and international academic cooperation partners. Bachelor and doctoral students will actively participate in the project, creating new research positions and promoting the dissemination of knowledge, publishing the results in high-impact scientific journals.Skin and soft tissue infections are one of the most common bacterial infections in humans. Bacteria that cause SSTIs are increasingly resistant to commonly used antibiotics and currently constitute one of the main categories of nosocomial pathogens. AMP is a promising alternative to conventional antibiotics because they act against different strains of bacteria and fungi. However, current AMP production methods, such as semi-automated solid phase synthesis, are inefficient and environmentally harmful. There is a growing interest in biological approaches to AMP production. Relatively low costs and easy scalability make biotechnological methods an attractive alternative to the production of AMP. To date, Escherichia coli is the most widely used host due to the established protocols and efficiency in protein production, but has significant limitations. We propose that the ethanol-synthesizing alpha proteobacteria Zymomonas mobile could be a better alternative to the production of E. coli antimicrobials for the treatment of SSTIs, with the additional potential to produce specific wound healing compounds. Z. mobile is an optional anaerobic bacterium known for its natural antimicrobial activity due to aerobic fermentation acid by-products. In addition, we have proven that the Z. mobile shows extremely high resistance to a series of strong AMPs, which makes it a promising AMP manufacturer. Unlike E. coli, which is not a GRAS (commonly recognised as safe) micro-organism, Z. mobile is not cytotoxic to dermal cell lines and is classified as a GRAS micro-organism. Therefore, its use in the production of AMP could eliminate the need for extensive stages of final product purification, as Z. mobile cell extracts containing AMP could be used directly in final products, following the practice of the cosmetics industry.Z. mobile is a well-known manufacturer of levan, a fructose biopolymer with important medical properties, in particular for wound healing. In this project, levane production will be strategically integrated with high-efficiency AMP expression Z. mobile under optimized conditions to maximize both levane and AMP outputs. By ensuring the simultaneous production of Levane and AMP in one cultivation process, the Z. mobile bacterial platform will reduce production costs and prevent the use of hazardous solvents in the post-treatment process. Thus, this Z. mobile platform will provide an environmentally sustainable and cost-effective solution, providing improved therapeutic efficiency in the treatment of SSTIs and wound healing. The project aims to exploit the potential of Z. mobile for the production of AMP, as well as its natural antimicrobial and levane production capabilities to create a multimodal bacterial platform, optimize the production of compounds for the treatment of skin and soft tissue infections.The main activities of the project: The main activities of the project for the development and optimization of the Zymomonas mobile-based manufacturing platform are: heterologous expression of AMP, assessment of AMP synergies with the natural antimicrobial activity of the Z. mobile strain, optimization of the methodology for the simultaneous extraction of levan and AMP, as well as evaluation of in vitro safety and efficacy. Technological scaling of the developed platform is envisaged. Planned results of the project: As a result, the most effective producer (strain) will be identified and a validated experimental protocol will be developed. The experimental protocol describing the AMP and Levane extraction and precipitation methodology has been developed, as well as publicity for the dissemination of the project results has been ensured. Expected economic impact: The planned results of the project contribute to the development of biomedical, medical technologies and pharmaceuticals by developing an innovative biotechnological platform for the production of antimicrobial peptides (AMPs) and Levane with application in the treatment of skin and soft tissue infections. The project also contributes to the development of a knowledge-intensive bioeconomy by optimising AMP and Levane biotechnological production methods. Areas of smart specialisation: biomedicine, medical technologies and biotechnologies, knowledge intensive bioeconomy Research areas (Frascati): 1.6. Biological sciences

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