| 1. |
- Åkesson, Per, et al.
(författare)
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Streptococcal inhibitor of complement-mediated lysis (SIC): an anti-inflammatory virulence determinant
- 2010
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Ingår i: Microbiology. - : Microbiology Society. - 1465-2080 .- 1350-0872. ; 156, s. 3660-3668
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Tidskriftsartikel (refereegranskat)abstract
- Since the late 1980s, a worldwide increase of severe Streptococcus pyogenes infections has been associated with strains of the M1 serotype, strains which all secrete the streptococcal inhibitor of complement-mediated lysis (SIC). Previous work has shown that SIC blocks complement-mediated haemolysis, inhibits the activity of antibacterial peptides and has affinity for the human plasma proteins clusterin and histidine-rich glycoprotein; the latter is a member of the cystatin protein family. The present work demonstrates that SIC binds to cystatin C, high-molecular-mass kininogen (HK) and low-molecular-mass kininogen, which are additional members of this protein family. The binding sites in HK are located in the cystatin-like domain D3 and the endothelial cell-binding domain D5. Immobilization of HK to cellular structures plays a central role in activation of the human contact system. SIC was found to inhibit the binding of HK to endothelial cells, and to reduce contact activation as measured by prolonged blood clotting time and impaired release of bradykinin. These results suggest that SIC modifies host defence systems, which may contribute to the virulence of S. pyogenes strains of the M1 serotype.
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| 2. |
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| 3. |
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| 4. |
- Holm, Karin, et al.
(författare)
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Activation of the contact system at the surface of Fusobacterium necrophorum: a possible virulence mechanism in Lemierre's syndrome.
- 2011
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Ingår i: Infection and Immunity. - 1098-5522. ; 79:8, s. 3284-3290
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Tidskriftsartikel (refereegranskat)abstract
- Fusobacterium necrophorum causes Lemièrre's syndrome, a serious disease with septic thrombophlebitis of the internal jugular vein, pulmonary involvement and systemic inflammation. The contact system is a link between inflammation and coagulation and contact activation by the bacteria could therefore contribute to the abnormal coagulation and inflammation seen in patients with Lemièrre's syndrome. In this study, F. necrophorum was found to bind radiolabeled high molecular weight kininogen (HK), a central component of the contact system. Binding was inhibited by the addition of unlabeled HK and domain D5 of HK, but not by other components of the contact system, indicating a specific interaction mediated through the D5 region. Binding of HK was significantly reduced after pre-treatment of the bacteria with trypsin, suggesting that surface proteins are involved in HK binding. Incubation of the bacteria with human plasma resulted in a breakdown pattern of HK suggestive of bradykinin release, and bradykinin was also detected in the supernatant. In addition, we show that factor XI (FXI), another component of the contact system, binds to F. necrophorum, and that the bound FXI reconstitutes the activated partial thromboplastin time (aPTT) of FXI-deficient plasma. Thrombin activity was detected at the surface of the bacteria following incubation with plasma, indicating that the intrinsic pathway of coagulation is activated at the surface. This activity was completely blocked by inhibitors of the contact system. The combined results show that the contact system is activated at the surface of F. necrophorum, suggesting a pathogenic role for this system in Lemièrre's syndrome.
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| 5. |
- Holm, Karin, et al.
(författare)
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Binding and activation of plasminogen at the surface of Fusobacterium necrophorum.
- 2013
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Ingår i: Microbial Pathogenesis. - : Elsevier BV. - 1096-1208 .- 0882-4010. ; 59-60:April,12, s. 29-32
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Tidskriftsartikel (refereegranskat)abstract
- Fusobacterium necrophorum is a gram-negative, anaerobic bacterium, which has been suggested to be a normal inhabitant of the oral flora. In rare cases, it can invade the tonsils and deeper tissues, causing the serious condition Lemièrre's syndrome. Recruitment of host plasminogen is a well-known bacterial virulence mechanism, and plasmin activity at the bacterial surface is thought to be important for bacterial invasion. Herein we show that plasminogen can be recruited to the surface of F. necrophorum, that surface-bound plasminogen is more easily converted to active plasmin than plasminogen in buffer, and that bound plasminogen is protected against inactivation by α2-antiplasmin. These findings add to the understanding of the pathogenesis of Lemièrre's syndrome.
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| 6. |
- Holmberg, Anna, et al.
(författare)
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Antibiotic regimens with rifampicin for treatment of Enterococcus faecium in biofilms.
- 2014
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 44:1, s. 78-80
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Tidskriftsartikel (refereegranskat)abstract
- Enterococcus faecium is an important pathogen that is resistant to many antibiotics and is able to form biofilms on implanted medical devices. In this study, the efficacy of rifampicin-containing antibiotic regimens against biofilms of E. faecium in vitro was investigated by determination of the minimum biofilm eradication concentration and by time-kill experiments of bacteria in biofilms formed on beads of bone cement. Rifampicin combined with tigecycline, daptomycin or linezolid was more efficient in reducing bacterial numbers and halting the development of rifampicin resistance than the combination of rifampicin and vancomycin.
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| 7. |
- Holmberg, Anna, et al.
(författare)
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Effectiveness of ciprofloxacin or linezolid in combination with rifampicin against Enterococcus faecalis in biofilms.
- 2012
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 67, s. 433-439
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo assess the in vitro antibiotic susceptibility of Enterococcus faecalis in biofilms.MethodsE. faecalis isolates were from infections of prosthetic hip and knee joints. Minimal biofilm eradication concentrations (MBECs) for ampicillin, vancomycin, linezolid, ciprofloxacin and rifampicin, alone and in combinations, were determined. E. faecalis biofilms in microtitre plate wells or on beads of bone cement were treated with the same antibiotics for various times followed by plating to quantify surviving bacteria.ResultsThe E. faecalis isolates displayed MBECs for the various antibiotics of between 64 and 512 mg/L. When combined with 8 mg/L rifampicin, MBECs for ciprofloxacin and linezolid dropped to 16-32 mg/L for the four isolates tested. In biofilms formed on a plastic surface and on bone cement beads significant bacterial killing (>2-3 log decrease in cfus) was seen after an 8 h exposure to antibiotics. For all isolates, the combination of ciprofloxacin and rifampicin, followed by linezolid and rifampicin, was most effective in reducing the number of bacteria. E. faecalis developed resistance to rifampicin in our system when biofilms were subjected to this antibiotic, alone or in combination with ampicillin. When bacteria were subjected to combinations with ciprofloxacin or linezolid development of resistance was reduced.ConclusionsOur results show that combinations of ciprofloxacin or linezolid with rifampicin have a good effect on E. faecalis biofilms in vitro. These combinations should be considered for testing in humans with early joint prosthesis infections with E. faecalis.
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| 8. |
- Inghammar, Malin, et al.
(författare)
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Recurrent erysipelas - risk factors and clinical presentation.
- 2014
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Erysipelas is a common infection that often recurs, but the impact of specific risk factors for reoccurrence remains elusive. In the present study we aimed at clarifying predisposing conditions for reoccurrence.
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| 9. |
- Johansson, Daniel, et al.
(författare)
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Platelet and neutrophil responses to gram positive pathogens in patients with bacteremic infection.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many Gram-positive pathogens aggregate and activate platelets in vitro and this has been proposed to contribute to virulence. Platelets can also form complexes with neutrophils but little is however known about platelet and platelet-neutrophil responses in bacterial infection. METHODOLOGY/PRINCIPAL FINDINGS: We added isolates of Gram-positive bacteria from 38 patients with a bacteremic infection to blood drawn from the same patient. Aggregometry and flow cytometry were used to assess platelet aggregation and to quantify activation of platelets, neutrophils, and platelet-neutrophils complexes (PNCs) induced by the bacteria. Fifteen healthy persons served as controls. Most isolates of Staphylococcus aureus, beta hemolytic streptococci, and Enterococcus faecalis induced aggregation of platelets from their respective hosts, whereas pneumococci failed to do so. S. aureus isolates induced platelet aggregation more rapidly in patients than in controls, whereas platelet activation by S. aureus was lower in patients than in controls. PNCs were more abundant in baseline samples from patients than in healthy controls and most bacterial isolates induced additional PNC formation and neutrophil activation. CONCLUSION/SIGNIFICANCE: We have demonstrated for the first time that bacteria isolated from patients with Gram-positive bacteremia can induce platelet activation and aggregation, PNC formation, and neutrophil activation in the same infected host. This underlines the significance of these interactions during infection, which could be a target for future therapies in sepsis.
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| 10. |
- Kahn, Fredrik, et al.
(författare)
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Axillary abscess complicated by venous thrombosis, identification of Streptococcus pyogenes by 16S PCR.
- 2010
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 48:9, s. 3435-3437
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Tidskriftsartikel (refereegranskat)abstract
- We report a case of an axillary abscess with Streptococcus pyogenes complicated by venous thrombosis. Bacterial etiology and typing was obtained by PCR and sequencing of the 16S rRNA and the M-protein genes from abscess material. The bacterium was of M41 serotype and serology indicated that it had expressed pro-coagulant factors.
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