fibrin and Gram-Positive-Bacterial-Infections

Infectious endocarditis (IE) remains one of the deadliest heart diseases with a high death rate, generally following thrombo-embolic events. Today, therapy is based on surgery and antibiotic therapy. When thromboembolic complications in IE patients persist, this is often due to our lack of knowledge regarding the pathophysiological development and organization of cells in the vegetation, most notably the primordial role of platelets and further triggered hemostasis, which is related to the diversity of infectious microorganisms involved. Our objective was to study the organization of IE vegetations due to different bacteria species in order to understand the related pathophysiological mechanism of vegetation development. We present an approach for ultrastructural analysis of whole-infected heart valve tissue based on scanning electron microscopy and energy-dispersive X-ray spectroscopy. Our approach allowed us to detect differences in cell organization between the analyzed vegetations and revealed a distinct chemical feature in

Topics: Aged; Aged, 80 and over; Blood Platelets; Endocarditis, Bacterial; Female; Fibrin; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Heart Valves; Humans; Inflammation; Male; Microscopy, Electron, Scanning; Middle Aged; Spectrometry, X-Ray Emission

Topics: Aged, 80 and over; Anti-Bacterial Agents; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Central Venous Catheters; Device Removal; Echocardiography, Transesophageal; Endocarditis, Bacterial; Enterococcus faecalis; Female; Fibrin; Gram-Positive Bacterial Infections; Humans; Kidney Failure, Chronic; Predictive Value of Tests; Renal Dialysis; Thrombosis; Treatment Outcome

The purpose of this study was to determine to what extent blood-retinal barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability.. Mice were intravitreally injected with 100 colony-forming units of B. cereus, and eyes were analyzed at specific times after infection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the retinal pigment epithelium.. B. cereus induced the leakage of albumin and fibrin into the aqueous and vitreous humor by 8 hours after infection. BRB permeability occurred as early as 4 hours and increased 13.30-fold compared with uninfected controls by 8 hours. Production of proinflammatory cytokines IL-6, MIP-1alpha, IL-1beta, and KC increased over the course of infection. In the retina, ZO-1 disruption began by 4 hours and was followed by decreasing occludin and ZO-1 expression at 4 and 8 hours, respectively. Tubulin condensation and RPE65 degradation occurred by 12 hours. A quorum-sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Wild-type and mutant B. cereus sterile supernatants induced blood-ocular barrier permeability similarly to that of wild-type infection.. These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 hours after infection. Disruption of tight junctions at the level of the retinal pigment epithelium may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability.

Topics: Animals; Aqueous Humor; Bacillus cereus; Blood-Retinal Barrier; Blotting, Western; Capillary Permeability; Cytokines; Endophthalmitis; Fibrin; Fluorescent Antibody Technique, Indirect; Gram-Positive Bacterial Infections; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Occludin; Phosphoproteins; Serum Albumin; Tight Junctions; Vitreous Body; Zonula Occludens-1 Protein

Topics: Blood Platelets; Cell Adhesion; Fibrin; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Host-Pathogen Interactions; Humans; Immune Evasion; Platelet Activation; Respiratory Tract Infections; Thrombospondin 1; Virulence

Infectious endocarditis is a microbial infection of the endothelial lining of the heart that typically occurs on damaged or prosthetic heart valves. The characteristic lesion seen with infective endocarditis, termed "the vegetation," is composed of bacteria surrounded by a platelet/fibrin layer attached to the underlying endothelium. The vegetation has long been believed to exclude or hinder host defenses from clearing bacteria, although formal demonstration of mechanisms by which this occurs are lacking. This study investigated the ability of the vegetation to exclude host antibodies specific for the bacterial surface protein aggregation substance in vivo during experimental endocarditis caused by Enterococcus faecalis. The results demonstrate that, once the vegetation encloses bacteria, they are no longer accessible to high-titer bacterial-specific host antibodies, establishing a mechanism by which the vegetation functions to protect the bacteria from the humoral immune response.

Topics: Animals; Antibodies, Bacterial; Antibody Specificity; Bacterial Proteins; Bacterial Vaccines; Blood Platelets; Endocarditis, Bacterial; Enterococcus faecalis; Fibrin; Gram-Positive Bacterial Infections; Immunization; Immunohistochemistry; Rabbits