Synergistic action of a photosensitizer and antimicrobial peptides for superbugs destruction – SAFEST

The project is organized into several steps to cover all its aspects:

1. Design of new molecules – combining antimicrobial peptides with photosensitizers.

2. Light-activated studies – understanding how these molecules behave upon exposure to light.

3. Interactions with bacteria – investigating how the molecules bind to and act on bacterial membranes.

4. Evaluation of antibacterial activity – testing their effects on different types of bacteria, including resistant strains.

5. Hydrogel development – preparing a gel based on the most promising compound for the treatment of skin wounds and oral infections.

1. Several antibacterial agents have been successfully synthesized.

They result from the combination of photosensitizers, molecules that become active when exposed to light, and antimicrobial peptides, which specifically target and bind to bacterial membranes.

2. Studies have shown that these new molecules can be activated by low-energy light.

They also emit light themselves, which allows them to be detected. Moreover, they exhibit an essential property: when activated by light, they react with oxygen to produce reactive species capable of destroying bacteria.

3. Further studies confirmed that the combination of photosensitizer and antimicrobial peptide effectively targets bacteria. Using high-resolution microscopy, it was possible to visualize these agents on the surface of bacterial membranes.

4. The first results are very promising. Complete eradication of E. coli and S. aureus was achieved with a low dose of a first synthesized antibacterial agent after activation by light.

The synergistic effect of the light–photosensitizer–antimicrobial peptide combination is clearly demonstrated: neither the antibacterial agent alone, nor the peptide alone, nor the light alone can destroy these bacteria under the same conditions.

These promising results open up important perspectives for the continuation of the project.

Future work will focus on evaluating the efficacy of these compounds against a broader range of multidrug-resistant bacterial strains.

In parallel, additional molecules will be designed and synthesized to deepen the understanding of the relationship between molecular structure and antibacterial activity, with the aim of optimizing their performance.

Finally, the most effective antibacterial candidate will be selected for incorporation into a hydrogel, paving the way for the development of innovative topical treatments for skin wounds and periodontal infections.

The fast spread of multi-resistant microorganisms represents a threat to public health that urgently needs new therapeutic approaches less prone to the development of resistant strains. Our objectives are the design, synthesis and in-depth biophysical studies of new antimicrobial peptide-photosensitizer (AMP-PS) conjugates for synergistic and selective inactivation of pathogens. The chosen AMPs will selectively drive the porphyrinic PS inside the bacteria while near IR light excitation will destroy them by creation of reactive oxygen species (ROS), without inducing bacterial resistance or damage to host tissues. This photoinactivation approach provides a promising treatment for chronic skin and periodontal infections. Thus, an AMP-PS hydrogel will be developed for topical applications. A consortium of three partners specialized in peptide and porphyrin synthesis, biophysical and antibacterial studies, and design of biomaterials, will provide the skills and implementation necessary for the success of the project.