PMID- 32444905 OWN - NLM STAT- MEDLINE DCOM- 20210930 LR - 20210930 IS - 1861-0692 (Electronic) IS - 1861-0684 (Print) IS - 1861-0684 (Linking) VI - 110 IP - 3 DP - 2021 Mar TI - Bacterial biofilms in infective endocarditis: an in vitro model to investigate emerging technologies of antimicrobial cardiovascular device coatings. PG - 323-331 LID - 10.1007/s00392-020-01669-y [doi] AB - OBJECTIVE: In spite of the progress in antimicrobial and surgical therapy, infective endocarditis (IE) is still associated with a high morbidity and mortality. IE is characterized by bacterial biofilms of the endocardium, especially of the aortic and mitral valve leading to their destruction. About one quarter of patients with formal surgery indication cannot undergo surgery. This group of patients needs further options of therapy, but due to a lack of models for IE prospects of research are low. Therefore, the purpose of this project was to establish an in vitro model of infective endocarditis to allow growth of bacterial biofilms on porcine aortic valves, serving as baseline for further research. METHODS AND RESULTS: A pulsatile two-chamber circulation model was constructed that kept native porcine aortic valves under sterile, physiologic hemodynamic and temperature conditions. To create biofilms on porcine aortic valves the system was inoculated with Staphylococcus epidermidis PIA 8400. Aortic roots were incubated in the model for increasing periods of time (24 h and 40 h) and bacterial titration (1.5 x 10(4) CFU/mL and 1.5 x 10(5) CFU/mL) with 5 L cardiac output per minute. After incubation, tissue sections were analysed by fluorescence in situ hybridization (FISH) for direct visualization of the biofilms. Pilot tests for biofilm growth showed monospecies colonization consisting of cocci with time- and inocula-dependent increase after 24 h and 40 h (n = 4). In n = 3 experiments for 24 h, with the same inocula, FISH visualized biofilms with ribosome-containing, and thus metabolic active cocci, tissue infiltration and similar colonization pattern as observed by the FISH in human IE heart valves infected by S. epidermidis. CONCLUSION: These results demonstrate the establishment of a novel in vitro model for bacterial biofilm growth on porcine aortic roots mimicking IE. The model will allow to identify predilection sites of valves for bacterial adhesion and biofilm growth and it may serve as baseline for further research on IE therapy and prevention, e.g. the development of antimicrobial transcatheter approaches to IE. FAU - Lauten, Alexander AU - Lauten A AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Standort Berlin, Berlin, Germany. Alexander.Lauten@charite.de. AD - Department of Cardiology, Charite, Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany. Alexander.Lauten@charite.de. AD - Department of General and Interventional Cardiology and Rhythmology, HELIOS Klinikum Erfurt, Erfurt, Germany. Alexander.Lauten@charite.de. AD - Devie Medical GmbH, Bachstr. 18, 7743, Jena, Deutschland. Alexander.Lauten@charite.de. FAU - Martinovic, Marc AU - Martinovic M AUID- ORCID: 0000-0002-9102-7975 AD - Department of Cardiology, Charite, Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany. Marc.Martinovic@charite.de. FAU - Kursawe, Laura AU - Kursawe L AD - Biofilmcenter, Department of Microbiology, Infectious Diseases and Immunology, Charite, Universitaetsmedizin Berlin, Berlin, Germany. FAU - Kikhney, Judith AU - Kikhney J AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Standort Berlin, Berlin, Germany. AD - Biofilmcenter, Department of Microbiology, Infectious Diseases and Immunology, Charite, Universitaetsmedizin Berlin, Berlin, Germany. FAU - Affeld, Klaus AU - Affeld K AD - Institute for Cardiovascular Computer-Assisted Medicine, Labor fur Biofluidmechanik, Charite, Universitaetsmedizin Berlin, Berlin, Germany. FAU - Kertzscher, Ulrich AU - Kertzscher U AD - Institute for Cardiovascular Computer-Assisted Medicine, Labor fur Biofluidmechanik, Charite, Universitaetsmedizin Berlin, Berlin, Germany. FAU - Falk, Volkmar AU - Falk V AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Standort Berlin, Berlin, Germany. AD - Department of Cardiology, Charite, Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany. AD - Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, Berlin, Germany. FAU - Moter, Annette AU - Moter A AD - Biofilmcenter, Department of Microbiology, Infectious Diseases and Immunology, Charite, Universitaetsmedizin Berlin, Berlin, Germany. LA - eng GR - Otto-Hess-Promotionsstipendium/Deutsche Gesellschaft fur Kardiologie-Herz und Kreislaufforschung./ PT - Journal Article DEP - 20200522 PL - Germany TA - Clin Res Cardiol JT - Clinical research in cardiology : official journal of the German Cardiac Society JID - 101264123 RN - 0 (Anti-Bacterial Agents) RN - 0 (Coated Materials, Biocompatible) SB - IM MH - Animals MH - Anti-Bacterial Agents/*pharmacology MH - Aortic Valve/*microbiology MH - Bacteria/*drug effects MH - *Biofilms MH - Coated Materials, Biocompatible MH - Disease Models, Animal MH - Endocarditis, Bacterial/drug therapy/*microbiology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mitral Valve/*microbiology MH - Prosthesis-Related Infections/drug therapy/*microbiology MH - Swine PMC - PMC7907033 OTO - NOTNLM OT - Biofilm OT - Bioreactor OT - Fluorescence in situ hybridization OT - In vitro model OT - Infective endocarditis OT - Staphylococcus epidermidis COIS- On behalf of all authors, the corresponding author states that there is no conflict of interest. EDAT- 2020/05/24 06:00 MHDA- 2021/10/01 06:00 PMCR- 2020/05/22 CRDT- 2020/05/24 06:00 PHST- 2019/07/05 00:00 [received] PHST- 2020/05/08 00:00 [accepted] PHST- 2020/05/24 06:00 [pubmed] PHST- 2021/10/01 06:00 [medline] PHST- 2020/05/24 06:00 [entrez] PHST- 2020/05/22 00:00 [pmc-release] AID - 10.1007/s00392-020-01669-y [pii] AID - 1669 [pii] AID - 10.1007/s00392-020-01669-y [doi] PST - ppublish SO - Clin Res Cardiol. 2021 Mar;110(3):323-331. doi: 10.1007/s00392-020-01669-y. Epub 2020 May 22.