Early Fibrin Biofilm Development in Cardiovascular Infections

The single most common microbe causing cardiovascular infections is Staphylococcus aureus (S. aureus). S. aureus produces coagulase that converts fibrinogen to fibrin, which is incorporated into biofilms. This process aids in adherence to intravascular structures, defense against the host immune system, and resistance to antimicrobial treatment. Despite its significance, fibrin formation in S. aureus biofilms remains poorly understood. Therefore, this study aimed to elucidate the early development of cardiovascular biofilms. Clinically isolated coagulase-positive S. aureus and coagulase-negative Streptococcus gordonii (S. gordonii) from patients with cardiovascular infections, and a coagulase mutant S. aureus {Delta}coa, were grown in tryptic soy broth (TSB), Iscoves Modified Dulbeccos Medium (IMDM), and pooled human plasma, with or without porcine heart valves. Bacterial growth, metabolic activity, and bacterial fibrinogen utilization were measured over 24 hr at 37 {degrees}C. Time-lapse confocal microscopy was used to visualize and track biofilm development. S. aureus exhibited more growth in TSB and human plasma than S. gordonii and S. aureus {Delta}coa, but showed similar growth as S. aureus {Delta}coa in IMDM. Peak metabolic activity for all isolates was highest in TSB and lowest in human plasma. The presence of porcine valves caused strain-dependent alterations in time to peak metabolic activity. Confocal imaging revealed fibrin-based biofilm development exclusively in the coagulase-producing S. aureus strains. Between 2 and 6 hr of biofilm development, 74.9% (p=0.034) of the fibrinogen from the medium was converted to fibrin. Variations in fibrin network porosity and density were observed among different coagulase-producing S. aureus strains. Fibrin formation is mediated by S. aureus coagulase and first strands occurred within 3 hr for clinical strains after exposure to human plasma. This study stresses the importance of experimental design given the bacterial changes due to different media and substrates and provides insights into the early pathogenesis of S. aureus cardiovascular biofilms. HighlightsO_LIBacterial growth and activity are medium and substrate dependent C_LIO_LICoagulase is necessary for Staphylococcus aureus fibrin biofilm development C_LIO_LIFibrin strands begin forming in Staphylococcus aureus biofilms within 3 hours C_LI