Inhibiting platelets aggregation could aggravate the acute infection caused by Staphylococcus aureus

Several fibrinogen binding proteins (Fibs) play important roles in the pathogenesis of Staphylococcus aureus (S. aureus). Most Fibs can promote the aggregation of platelets during infection, but the extracellular fibrinogen-binding protein (Efb) is an exception. It is reported that Efb can specifically bind fibrinogen and inhibit the aggregation of platelet with its N terminal. However, the biological significance of platelet aggregation inhibition in the infection caused by S. aureus is unclear until now. Here, we demonstrated that the persistence and aggregation of platelets were important for killing S. aureus in whole blood. It was found that the N terminal of Efb (EfbN) and platelets inhibitors could increase the survival of S. aureus in whole blood. The study in vivo also showed that EfbN and platelets inhibitors could reduce the killing of S. aureus and increase the lethality rate of S. aureus in the acute infection mouse model.     

Inhibiting platelets aggregation could aggravate the acute infection caused by Staphylococcus aureus

Several fibrinogen binding proteins (Fibs) play important roles in the pathogenesis of Staphylococcus aureus (S. aureus). Most Fibs can promote the aggregation of platelets during infection, but the extracellular fibrinogen-binding protein (Efb) is an exception. It is reported that Efb can specifically bind fibrinogen and inhibit the aggregation of platelet with its N terminal. However, the biological significance of platelet aggregation inhibition in the infection caused by S. aureus is unclear until now. Here, we demonstrated that the persistence and aggregation of platelets were important for killing S. aureus in whole blood. It was found that the N terminal of Efb (EfbN) and platelets inhibitors could increase the survival of S. aureus in whole blood. The study in vivo also showed that EfbN and platelets inhibitors could reduce the killing of S. aureus and increase the lethality rate of S. aureus in the acute infection mouse model.     

Capsular polysaccharide masks clumping factor A-mediated adherence of Staphylococcus aureus to fibrinogen and platelets

BACKGROUND: Clumping factor A (ClfA) is a Staphylococcus aureus cell wall-associated adhesin that mediates staphylococcal binding to fibrinogen and platelets. Our goals were to determine whether expression of capsular polysaccharide (CP) affected ClfA-mediated adherence of S. aureus and to assess whether the length of the ClfA repeat region influenced this interaction. METHODS: ClfA constructs with repeat regions of different lengths were introduced into isogenic S. aureus strains that expressed CP5, CP8, or no CP. S. aureus binding to fibrinogen was assessed in rabbit plasma and on fibrinogen-coated microtiter plates. Adherence of S. aureus strains to platelets was evaluated by flow cytometry and confocal microscopy. RESULTS: As the length of the ClfA repeat region increased, binding of acapsular S. aureus to fibrinogen-coated microtiter plates was enhanced. By contrast, encapsulated S. aureus expressing the full-length ClfA were poorly adherent. The acapsular S. aureus mutant strain showed a 2-fold increase in platelet binding, compared with the isogenic encapsulated strains. By contrast, platelet aggregation was unaffected by CP production. CONCLUSION: CP expression inhibits S. aureus ClfA-mediated binding to fibrinogen and platelets, and a full-length repeat region cannot overcome this inhibition. These findings have important implications for vaccine development, given that CP may mask surface adhesins.     

Staphylococcus aureus fibronectin-binding protein (FnBP)-mediated adherence to platelets, and aggregation of platelets induced by FnBPA but not by FnBPB

BACKGROUND: The ability of Staphylococcus aureus to adhere to platelets and to induce aggregation of platelets is considered to be a critical factor in S. aureus-associated infective endocarditis. METHODS: To identify and characterize further bacterial factors involved in the S. aureus-platelet interaction, we generated a phage-display library of S. aureus genomic DNA by use of the improved phagemid vector pG8SAET. The library was affinity-panned against gel-filtered, immobilized platelets. RESULTS: Repeatedly isolated clones contained overlapping DNA fragments encoding a portion of the S. aureus fibronectin (Fn)-binding proteins (FnBPs). In a flow cytometric adherence assay, Staphylococcus carnosus that heterologously expressed either fnbA or fnbB, which encode FnBPA and FnBPB, respectively, showed increased adherence to activated, gel-filtered platelets. Adherence was promoted by the addition of Fn or fibrinogen (Fg), which most likely act as bridging molecules. Interestingly, promotion of adherence mediated by Fn was in the same range with S. carnosus producing either FnBPA or FnBPB, whereas promotion of adherence mediated by Fg was significantly more pronounced with S. carnosus that produce FnBPA than with S. carnosus that produce FnBPB. Furthermore, FnBPA, but not FnBPB, mediated aggregation of platelets when present on S. carnosus cells. CONCLUSION: Our results indicate a substantial functional difference between FnBPA and FnBPB in the S. aureus-platelet interaction.     

Update on the epidemiology and management of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, in patients with cystic fibrosis

PURPOSE OF REVIEW: Staphylococcus aureus is one of the first and most common pathogens to be isolated from the respiratory tract of patients with cystic fibrosis. The prevalence of respiratory tract colonization/infection with both methicillin-susceptible and methicillin-resistant S. aureus has increased over the past decade. The clinical significance of colonization/infection with these pathogens is variable, leading to numerous therapeutic strategies: primary prophylaxis, eradication, treatment of cystic fiboris pulmonary exacerbations, and treatment of methicillin-resistant S. aureus. RECENT FINDINGS: Studies have demonstrated increased prevalence of S. aureus in clinical laboratories that use selective media. Additionally, small colony variant S. aureus has been associated with persistent infection, co-infection with Pseudomonas aeruginosa, and frequent courses of antibiotics, but this phenotype may be difficult to identify in clinical laboratories. Increased prevalence of methicillin-resistant S. aureus has led to use of oral and inhaled antibiotics in attempts to eradicate this pathogen; these studies have yielded variable results. SUMMARY: The epidemiology of S. aureus in cystic fibrosis has changed. Studies are needed to assess the clinical significance of the increased prevalence of both methicillin-susceptible and methicillin-resistant S. aureus, and whether primary prophylaxis or new treatment/eradication protocols are effective.     

Activated platelets mediate Staphylococcus aureus deposition on subendothelial extracellular matrix: the role of glycoprotein Ib

Extracellular matrix (ECM) derived from bovine corneal endothelial cells was used as a model to study the role of platelets in Staphylococcus aureus interaction with the vascular subendothelium. In whole blood, S. aureus activated platelets, as demonstrated by P-selectin expression on the platelet membrane. Subjecting platelet-rich plasma (PRP) to the ECM under oscillatory conditions resulted in platelet adhesion and aggregation. S. aureus increased platelet deposition on ECM depending on the bacterium-platelet ratio. Scanning electron microscopy revealed that S. aureus adhered to and formed clusters on ECM-bound platelets. These findings were confirmed by using [3H]thymidine-labeled bacteria that adhered to the surface more extensively after deposition of platelets on ECM. Platelet pre-treatment with prostaglandin E1 resulted in inhibition of bacterial adherence. Glycoprotein (GP)Ib was involved in the bacterium-platelet interaction, as indicated by the following: (i) S. aureus diminished the binding of GPIb but not of GPIX or GPIIb-IIIa monoclonal antibodies (Mab) to washed fixed platelets; (ii) GPIb Mab inhibited S. aureus -induced platelet aggregation in a dose-dependent fashion; (iii) blockade of von Willebrand factor (vWf) binding to GPIb by a recombinant vWf fragment reversed the enhanced platelet deposition on ECM in the presence of S. aureus but did not affect platelet deposition in the absence of bacteria. The results indicate that S. aureus activates platelets and promotes their deposition on ECM via GPIb-dependent mechanism and that adherent platelets mediate S. aureus deposition on the subendothelium. These interactions might play a role in the pathogenesis of bacterial endocarditis.     

Activated platelets mediate Staphylococcus aureus deposition on subendothelial extracellular matrix: the role of glycoprotein Ib

Extracellular matrix (ECM) derived from bovine corneal endothelial cells was used as a model to study the role of platelets in Staphylococcus aureus interaction with the vascular subendothelium. In whole blood, S. aureus activated platelets, as demonstrated by P-selectin expression on the platelet membrane. Subjecting platelet-rich plasma (PRP) to the ECM under oscillatory conditions resulted in platelet adhesion and aggregation. S. aureus increased platelet deposition on ECM depending on the bacterium-platelet ratio. Scanning electron microscopy revealed that S. aureus adhered to and formed clusters on ECM-bound platelets. These findings were confirmed by using [3H]thymidine-labeled bacteria that adhered to the surface more extensively after deposition of platelets on ECM. Platelet pre-treatment with prostaglandin E1 resulted in inhibition of bacterial adherence. Glycoprotein (GP)Ib was involved in the bacterium-platelet interaction, as indicated by the following: (i) S. aureus diminished the binding of GPIb but not of GPIX or GPIIb-IIIa monoclonal antibodies (Mab) to washed fixed platelets; (ii) GPIb Mab inhibited S. aureus -induced platelet aggregation in a dose-dependent fashion; (iii) blockade of von Willebrand factor (vWf) binding to GPIb by a recombinant vWf fragment reversed the enhanced platelet deposition on ECM in the presence of S. aureus but did not affect platelet deposition in the absence of bacteria. The results indicate that S. aureus activates platelets and promotes their deposition on ECM via GPIb-dependent mechanism and that adherent platelets mediate S. aureus deposition on the subendothelium. These interactions might play a role in the pathogenesis of bacterial endocarditis.     

Staphylococcus aureus endocarditis

Among 409 cases of bacterial endocarditis (BE) observed from 1972 to 1985, 142 were caused by Staphylococcus aureus. Of these 142 cases, 59 affected native valves of the left heart (left BE), 47 affected native valves of the right heart (right BE) (including 36 drug-addicts), and 36 involved prosthetic valves (BEP) and were associated with mediastinitis in 11 cases. Symptoms were acute in 122 cases and subacute in 2 cases. 91 of the BE on native valves were primary (86%). Cutaneous manifestations were present in 38 cases (27%). Of the 67 patients who died (47%), 28/59 had left BE (47%), 7/47 had right BE (15%) (including 2 drug addicts) and 32/36 had BEP (86%); all differences were statistically significant. Complications consisted of: heart failure in 78 cases (55%), including 40 cases of left BE, 8 cases of right BE and 30 cases of BEP; systemic peripheral embolism in 29 cases (left BE 17, BEP 12) and neurological accidents in 58 cases (left BE 34, right BE 24). Thirty of these accidents occurred before the 4th day (left BE 13, BEP 17). Documented neurological accidents included cerebral haemorrhage (13 cases), cerebral infarction (14 cases) and cerebral abscess (4 cases); 4 of the 12 patients who underwent arteriography were found to have one or several aneurysms. Thirty-nine of these 58 patients died, death being directly due to a neurological cause in 20 cases (left BE 10, right BE 10).(ABSTRACT TRUNCATED AT 250 WORDS)     

Community-acquired methicillin-resistant Staphylococcus aureus endomyocardial abscesses in a heart transplant recipient

Abstract: Infective endocarditis is more common in heart transplant recipients than in the general population. We report a case of endomyocardial abscesses and sepsis syndrome due to community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in a heart transplant recipient with a negative transesophageal echocardiogram. The suspected portal of entry for this MRSA infection was through infected herpes zoster lesions. This case demonstrates the difficulty of diagnosing endomyocardial abscesses in heart transplant patients.     

Daptomycin-nonsusceptible,vancomycin-intermediate,methicillin-resistant Staphylococcus aureus endocarditis

Due to the emergence of Staphylococcus aureus with reduced vancomycin susceptibility, newer antibiotics, including daptomycin, have been used to treat methicillin-resistant S aureus infections. Daptomycin is a cyclic lipopeptide that is approved to treat S aureus bacteremia and right-sided endocarditis, and reports of S aureus with reduced susceptibility to daptomycin are infrequent. To our knowledge, the present report describes the first Canadian case of daptomycin-nonsusceptible, vancomycin-intermediate S aureus infection.     

Staphylococcus aureus bacteremia and endocarditis

The prevalence of Stapylococcus bacteriaemia is increasing worldwide, because of the increasing use of invasive procedures leading to nosocomial infections, but also of a changing way of life (increasing fashion for tattoos or piercing, use of intravenous drugs). Infective endocarditis develops in 10-30% of the cases of staphylococcus bacteriaemia. Staphylococcus aureus endocarditis must be suspected when it develops in the year following heart surgery or implantation of permanent devices. In drug users, it usually involves the tricuspid valve. According to the resistance of the germ to meticillin, antibiotic therapy uses a combination of intravenous penicillin or glycopeptide and an aminoside. Other antibiotics such as fosfomycin, rifampicin, fusidic acid, or clindamycin can be used when aminosides are contra-indicated. The role of newer antibiotic agents, such as daptomycin or linezolide, remains to be established.     

Staphylococcus aureus bacteremia and endocarditis

Staphylococcus aureus is a leading cause of bacteremia and endocarditis. Over the past several years, the frequency of S. aureus bacteremia (SAB) has increased dramatically. This increasing frequency, coupled with increasing rates of antibiotic resistance, has renewed interest in this serious, common infection. S. aureus is a unique pathogen because of its virulent properties, its protean manifestations, and its ability to cause endocarditis on architecturally normal cardiac valves. Although the possibility of underlying endocarditis arises in virtually every patient with SAB, only a minority of bacteremic patients will actually have cardiac involvement. Distinguishing patients with S. aureus infective endocarditis (IE) from those with uncomplicated SAB is essential, but often difficult. In this review, the authors summarize recent changes in the epidemiology of SAB and IE, discuss the challenges in distinguishing SAB from IE, and discuss current trends in the management of patients with SAB and IE.     

Staphylococcus aureus bacteremia and endocarditis

Staphylococcus aureus is a leading cause of bacteremia and endocarditis. Over the past several years, the frequency of S aureus bacteremia (SAB) has increased dramatically. This increasing frequency, coupled with increasing rates of antibiotic resistance, has renewed interest in this serious, common infection. S aureus is a unique pathogen because of its virulent properties, its protean manifestations, and its ability to cause endocarditis on architecturally normal cardiac valves. Although the possibility of underlying endocarditis arises in virtually every patient with SAB, only a minority of bacteremic patients will actually have cardiac involvement. Distinguishing patients with S aureus infective endocarditis (IE) from those with uncomplicated SAB is essential, but often difficult. In this review, the authors summarize recent changes in the epidemiology of SAB and IE, discuss the challenges in distinguishing SAB from IE, and discuss current trends in the management of patients with SAB and IE.