Periodic Reporting for period 1 - PhotoLiB (Photoswitchable amphiphilic lipids: a photopharmacology strategy to combat drug-resistant bacterial infections.)
Okres sprawozdawczy: 2021-07-01 do 2023-06-30
In response to the escalating concern over antibiotic resistance, our research introduced an innovative strategy that combines photopharmacology principles with membrane-disrupting drugs. The core concept involved connecting cationic amphiphilic molecules with photoswitchable probes to modulate drug mobility and activity. This enhanced selectivity and accelerated bacterial membrane disruption.
The primary objectives of the research were successfully achieved: (1) developing new antibacterial drugs, Photoswitchable Amphiphilic Lipids (PALs), which interact with and disrupt bacterial membranes and cell walls upon light activation; (2) identifying PALs capable of disrupting bacterial membranes at different wavelengths, providing versatility; (3) exploring synergistic effects of PALs when combined with standard antibiotics to amplify antibiotic efficacy.
The compounds devised during the fellowship represent a unique approach where light serves as a modulator, employing a switch-on/off strategy to regulate their activity. This innovative mechanism enables the selective targeting of Gram-positive bacteria, minimizing exposure time and mitigating the risk of resistance development. The implications of this research point towards a groundbreaking strategy for the development of antibiotics with increased efficacy and reduced potential for resistance.
This research significantly aligns with the European research priority of "Antimicrobial Resistance," addressing a critical global health challenge. It transcends geographical boundaries and contributes to global public health, while also aligning with the objectives of European Health Systems and the interests of European industries. It establishes a crucial research foundation for innovative strategies and therapies against drug-resistant bacterial infections, enhancing healthcare practices, patient outcomes, and industry competitiveness.
In conclusion, this research goes beyond academia, offering real-world solutions aligned with European health priorities and the imperative for novel therapeutic strategies. The project has made a substantive and enduring contribution to the broader health landscape, particularly in the ongoing battle against antibiotic-resistant bacterial strains.
In addition, the researcher: (1) Gained extensive training in organic chemistry analytical techniques, including NMR, LCMS, and UV spectroscopy; (2) Facilitated a knowledge exchange, contributing strong medicinal chemistry and drug discovery expertise, while acquiring proficiency in organic synthesis, analytical chemistry, and microbiology through collaboration; (3) Actively managed the project by participating in scientific and non-scientific aspects, from executing experiments to scientific management; (4) Engaged in the financial management of the project, alongside the supervisor, ensuring efficient resource allocation; (5) Supervised master's students in drug discovery projects related to infectious diseases.
Overall, the project's results will be shared in a research paper co-authored primarily by the researcher, with valuable contributions from the supervisor and project collaborators.
Anticipated results until the end of the project are the development of a new class of antibacterial drugs, PALs, which exhibited unprecedented effectiveness in disrupting bacterial membranes and cell walls, thus eradicating bacteria. These compounds are poised to outperform existing antibiotics. By expanding the scope of antibacterial agents and increasing their selectivity, this research is likely to have significant impacts on the landscape of antibiotic drug discovery. In essence, the outcomes of this project transcend academia and extend into practical solutions to address antibiotic-resistant bacterial strains. Furthermore, it carries important socio-economic implications, as the potential success of this research can lead to novel therapeutic strategies against drug-resistant infections, potentially revolutionizing healthcare. It offers a substantial contribution to the global fight against antibiotic resistance and promises to make a lasting impact on societal and economic aspects related to healthcare and pharmaceuticals.