Research project

PRINT-AID project, PhD in Drug Research (2017-2021)

Supervised by Jari Yli-Kauhaluoma, Kirsi Savijoki and Adyary Fallarero, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Anti-infective research group, University of Helsinki, Finland

Title of thesis: Identification, mechanistic characterization and chemical optimization of repurposed anti-biofilms

Description: The doctoral project is part of the PRINT-AID network (Marie Sklodowska-Curie Actions, Innovative Training Networks, H2020-MSCA-ITN-2016) and contributes to the main goal of developing a new generation of personalized anti-infective 3D-printed medical devices. The objectives of the project are to identify new anti-biofilms, characterize their mechanism of action and select at least one lead for structural optimization and integration into a 3D-printed medical device. The discovery of new anti-biofilm candidates has been accomplished by high-throughput screening and follow-up studies are currently under way. One key compound has been selected for integration into a device prototype and testing in vivo. In parallel, structural optimization is in course in order to increase its potency and value as an anti-biofilm lead overall.

Tasks:

- Miniaturization and otpmization of an antimicrobial activity screening platform based on in vitro bacterial biofilms staining to 384-well microplates with two bacterial strains, S. aureus and P. aeruginosa.

- High-throughput evaluation of the preventive and destructive antimicrobial activity of libraries of compounds on bacterial biofilms using the optimized screening platform based on combined resazurin and crystal violet staining

- Characterization of the anti-biofilm activity using various techniques (ATP production, LIVE/DEAD staining and confocal microscopy, CFU count, MIC/MBC/MBIC determination with Calgary Biofilm Device, activity determination on numerous collection and clinical bacterial strains, cytotoxicity, etc)

- Investigation of the mode of action of the selected hits (killing kinetic, quorum sensing inhibition, membrane disruption assay, transcriptomics analysis, etc)

Academic Background

PhD in Drug Research (2017 - 2021), University of Helsinki, Finland

MSc in Microbiology-Immunology (2016), Laval University, Quebec City, Canada

BSc in Biomedical sciences (2014), Laval University, Quebec City, Canada

BSc in Biology (2014), Laval University, Quebec City, Canada

Publications

Gilbert-Girard S, Reigada I, Savijoki K, Yli-Kauhaluoma J, Fallarero A. Screening of natural compounds identifies ferutinin as an antibacterial and anti-biofilm compound. Biofouling. 2021. 37(7): p. 791-807.

Zore M*, Gilbert-Girard S*, Reigada I, Patel Z J., Savijoki K, Fallarero A, and Yli-Kauhaluoma J. Synthesis and Biological Evaluation of Fingolimod Derivatives as Antibacterial Agents. ACS Omega. 2021. 6(28): p. 18465-18486. (*equal contribution)

Reigada I, San-Martin-Galindo P, Gilbert-Girard S, Chiaro J, Cerullo V, Savijoki K, Nyman T A, Fallarero A, Miettinen I. Surfaceome and exoproteome dynamics in dual-species Pseudomonas aeruginosa and Staphylococcus aureus biofilms. Front Microbiol. 2021. 12: p. 672975.

Gilbert-Girard S, Savijoki K, Yli-Kauhaluoma J, Fallarero A. Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod. Microorganisms. 2020. 8(11): p. 1834.

Gilbert-Girard S, Savijoki K, Yli-Kauhaluoma J, Fallarero A. Optimization of a High-Throughput 384-Well Plate-Based Screening Platform with Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 15442 Biofilms. Int J Molec Sci. 2020. 21(9): p. 3034.

Fedorowicz, J., J. Saczewski, A. Konopacka, K. Waleron, D. Lejnowski, K. Ciura, T. Tomasic, Z. Skok, K. Savijoki, M. Morawska, S. Gilbert-Girard and A. Fallarero (2019). "Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents." Eur J Med Chem 179: 576-590.

Gilbert-Girard, S., Savijoki, K., Montoya, L., Fallarero, A. Assess the cellular viability of Staphylococcus aureus biofilms: PrestoBlue HS and alamarBlue HS reagents for microplate viability assays. Bioprobes 79: Journal of Cell Biology Applications, published by Thermo Fisher Scientific Inc. (http://assets.thermofisher.com/TFS-Assets/BID/Reference-Materials/bioprobes-79-journal.pdf)