TY - JOUR

T1 - Dynamics of a Staphylococcus aureus infective endocarditis simulation model

AU - Schwartz, Franziska A.

AU - Nielsen, Luna

AU - Struve Andersen, Jessica

AU - Bock, Magnus

AU - Christophersen, Lars

AU - Sunnerhagen, Torgny

AU - Lerche, Christian Johann

AU - Bay, Lene

AU - Bundgaard, Henning

AU - Høiby, Niels

AU - Moser, Claus

N1 - Publisher Copyright: © 2022 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.

PY - 2022

Y1 - 2022

N2 - Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24 h. The bacteria were organized in biofilm aggregates and displayed increased tolerance toward antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a Staphylococcus aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6 h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic-tolerant biofilms can be formed in our model already after 6 h, accelerating the screening for optimal treatment strategies for IE.

AB - Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegetation (IEV) model produced from whole venous blood, on which we achieved stable bacterial colonization after 24 h. The bacteria were organized in biofilm aggregates and displayed increased tolerance toward antibiotics. In this current study, we aimed at further characterizing the time course of biofilm formation and the impact on antibiotic tolerance development. We found that a Staphylococcus aureus reference strain, as well as three clinical IE isolates formed biofilms on the IEV after 6 h. When treatment was initiated immediately after infection, the antibiotic effect was significantly higher than when treatment was started after the biofilm was allowed to mature. We could follow the biofilm development microscopically by visualizing growing bacterial aggregates on the IEV. The findings indicate that mature, antibiotic-tolerant biofilms can be formed in our model already after 6 h, accelerating the screening for optimal treatment strategies for IE.

KW - antibiotic tolerance

KW - Biofilm

KW - histopathology

KW - host response

KW - infective endocarditis

KW - organoid

U2 - 10.1111/apm.13231

DO - 10.1111/apm.13231

M3 - Journal article

C2 - 35460117

AN - SCOPUS:85130719962

VL - 130

SP - 515

EP - 523

JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

SN - 0903-4641

IS - 8

ER -