The research group of Dr. S.A.J. Zaat at the Amsterdam UMC (location AMC) is part of the Department of Medical Microbiology. The research group focusses on pathogenesis, prevention and rapid diagnosis of biomaterial-associated infection (BAI) and other infections, and the development of novel antimicrobial strategies, particularly, of novel antimicrobial peptides. Infection of implanted medical devices (biomaterials), like catheters, prosthetic heart valves or orthopedic implants, can have disastrous consequences, including removal of the device. For still not well understood reasons, the presence of a foreign body strongly increases susceptibility to infection. The research is focused at understanding the high infection-susceptibility of tissue around biomaterials, by unravelling the molecular basis of the foreign body response and BAI, and to use this knowledge to develop novel antibacterial strategies to combat BAI. The most promising antimicrobial agents are novel Synthetic Antimicrobial and Anti-biofilm Peptides (SAAPs), active against multi-drug resistant bacteria in different in vivo settings. Recent work in collaboration with the associated industry partner BiosparQ (BSQ) on diagnostics focuses on development of the Cirrus-20 single cell MALDI-TOF system, eliminating the need for time-consuming culture by allowing almost instant diagnosis in clinical samples in minutes.

Within the AMC, the research is both fundamentally and translationally oriented, with strong links to the Departments of Cell Biology and Histology, Biochemistry and Pathology on the fundamental aspects, and, Gynecology, General Surgery, Intensive Care Medicine, Orthopedics and Anesthesiology on the clinical side. The group is part of the Amsterdam Infection and Immunity Institute (AI&II). For the antimicrobial peptide and antimicrobial biomaterials work in general, the BALI consortium partners and the EU COST Action partners of iPROMEDAI, AMiCI and ENIUS are the international embedding, including company partners such as Madam Therapeutics B.V. (The Netherlands), who valorize the novel antimicrobial peptides, and coating companies such as PolyPidLtd. (Israel). The link to the AO ResearchInstitute in Davos also provides a connection to the large company partner Synthes.

List of the most relevant references and project

Publications

K.W.J. Verhorstert, Z. Guler, L. de Boer, M. Riool, J.W.R. Roovers, S.A.J. Zaat, In Vitro Bacterial Adhesion and Biofilm Formation on Fully Absorbable Poly-4-hydroxybutyrate and Nonabsorbable Polypropylene Pelvic Floor Implants, ACS Appl. Mater. Interfaces. (2020) acsami.0c14668. doi:10.1021/acsami.0c14668.

I. Reigada, C. Guarch-Pérez, J.Z. Patel, M. Riool, K. Savijoki, J. Yli-Kauhaluoma, S.A.J. Zaat, A. Fallarero, Combined Effect of Naturally-Derived Biofilm Inhibitors and Differentiated HL-60 Cells in the Prevention of Staphylococcus aureus Biofilm Formation, Microorganisms. 8 (2020) 1757. doi:10.3390/microorganisms8111757.

M.I. Hofstee, M. Riool, I. Terjajevs, K. Thompson, M.J. Stoddart, R.G.G. Richards, S.A.J. Zaat, T.F.F. Moriarty, Three-Dimensional In Vitro Staphylococcus aureus Abscess Communities Display Antibiotic Tolerance and Protection from Neutrophil Clearance, Infect. Immun. 88 (2020) 1–16. doi:10.1128/IAI.00293-20.

P.P. Balraadjsing, E.C. de Jong, W.J.B. van Wamel, S.A.J. Zaat, Dendritic Cells Internalize Staphylococcus aureus More Efficiently than Staphylococcus epidermidis, but Do Not Differ in Induction of Antigen-Specific T Cell Proliferation, Microorganisms. 8 (2019) 19. doi:10.3390/microorganisms8010019.

B.C. Koppen, P.P.G. Mulder, L. de Boer, M. Riool, J.W. Drijfhout, S.A.J. Zaat, Synergistic microbicidal effect of cationic antimicrobial peptides and teicoplanin against planktonic and biofilm-encased Staphylococcus aureus, Int. J. Antimicrob. Agents. 53 (2019) 143–151. doi:10.1016/j.ijantimicag.2018.10.002.

M. Ramstedt, I.A.C. Ribeiro, H. Bujdakova, F.J.M. Mergulhão, L. Jordao, P. Thomsen, M. Alm, M. Burmølle, T. Vladkova, F. Can, M. Reches, M. Riool, A. Barros, R.L. Reis, E. Meaurio, J. Kikhney, A. Moter, S.A.J. Zaat, J. Sjollema, Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations, Macromol. Biosci. 1800384 (2019) 1800384. doi:10.1002/mabi.201800384.

X. Zhang, L. de Boer, L. Heiliegers, S. Man-Bovenkerk, P.K. Selbo, J.W. Drijfhout, A. Høgset, S.A.J. Zaat, Photochemical internalization enhances cytosolic release of antibiotic and increases its efficacy against staphylococcal infection, J. Control. Release. 283 (2018) 214–222. doi:10.1016/j.jconrel.2018.06.004.

A. de Breij, M. Riool, R.A. Cordfunke, N. Malanovic, L. de Boer, R.I. Koning, E. Ravensbergen, M. Franken, T. van der Heijde, B.K. Boekema, P.H.S. Kwakman, N. Kamp, A. El Ghalbzouri, K. Lohner, S.A.J. Zaat, J.W. Drijfhout, P.H. Nibbering, The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms, Sci. Transl. Med. 10 (2018) eaan4044. doi:10.1126/scitranslmed.aan4044.

J. Sjollema, S.A.J. Zaat, V. Fontaine, M. Ramstedt, R. Luginbuehl, K. Thevissen, J. Li, H.C. van der Mei, H.J. Busscher, In vitro methods for the evaluation of antimicrobial surface designs, Acta Biomater. (2018) 1–13. doi:10.1016/j.actbio.2018.02.001.

S. Zaccaria, R.C. van Gaal, M. Riool, S.A.J. Zaat, P.Y.W. Dankers, Antimicrobial peptide modification of biomaterials using supramolecular additives, J. Polym. Sci. Part A Polym. Chem. 56 (2018) 1926–1934. doi:10.1002/pola.29078.

Domestic and international projects

DARTBAC: Dutch antimicrobial resistance technology development and biofilm assessment consortium (Dutch National Science Agenda; 2021-2027)

STIMULUS: Stimuli responsive materials for the rapid detection and treatment of healthcare associated infections (EU H2020-MSCA-ITN; 2021-2025)

Biodegradable silica hydrogel based composite material for releasing resistance-free antimicrobial peptides (Dutch Research Council (NWO) – GDST; 2020-2023)

Development of a multicellular 3-dimensional in vitro model of bone infection (Clinical Priority Program of AO Trauma; 2017-2021)

SuperActive: Supramolecular biomaterials with antimicrobial and regenerative activity (Dutch Polymer Institute (DPI) – NEWPOL; 2017-2020)

PRINT-AID: Multidisciplinary European training network for development of personalized anti-infective medical devices combining printing technologies and antimicrobial functionality (EU H2020-MSCA-ITN; 2017-2021)

CRANIOSAFE: Optimized and innovative materials and customized treatment strategies for cranioplasty (Dutch Technology Foundation (STW); 2016-2021)

BALI: Biofilm alliance (EU FP7-HEALTH 2011-2016)