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4.
PLoS Pathog ; 6(8): e1001047, 2010 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-20714354

RESUMEN

The binding of bacteria to human platelets is a likely central mechanism in the pathogenesis of infective endocarditis. We have previously found that platelet binding by Streptococcus mitis SF100 is mediated by surface components encoded by a lysogenic bacteriophage, SM1. We now demonstrate that SM1-encoded lysin contributes to platelet binding via its direct interaction with fibrinogen. Far Western blotting of platelets revealed that fibrinogen was the major membrane-associated protein bound by lysin. Analysis of lysin binding with purified fibrinogen in vitro confirmed that these proteins could bind directly, and that this interaction was both saturable and inhibitable. Lysin bound both the Aalpha and Bbeta chains of fibrinogen, but not the gamma subunit. Binding of lysin to the Bbeta chain was further localized to a region within the fibrinogen D fragment. Disruption of the SF100 lysin gene resulted in an 83+/-3.1% reduction (mean +/- SD) in binding to immobilized fibrinogen by this mutant strain (PS1006). Preincubation of this isogenic mutant with purified lysin restored fibrinogen binding to wild type levels. When tested in a co-infection model of endocarditis, loss of lysin expression resulted in a significant reduction in virulence, as measured by achievable bacterial densities (CFU/g) within vegetations, kidneys, and spleens. These results indicate that bacteriophage-encoded lysin is a multifunctional protein, representing a new class of fibrinogen-binding proteins. Lysin appears to be cell wall-associated through its interaction with choline. Once on the bacterial surface, lysin can bind fibrinogen directly, which appears to be an important interaction for the pathogenesis of endocarditis.


Asunto(s)
Plaquetas/microbiología , Fibrinógeno/metabolismo , Mucoproteínas/metabolismo , Infecciones Estreptocócicas/metabolismo , Streptococcus mitis/patogenicidad , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Animales , Plaquetas/metabolismo , Western Blotting , Endocarditis Bacteriana/metabolismo , Endocarditis Bacteriana/virología , Humanos , Datos de Secuencia Molecular , Mucoproteínas/química , Mucoproteínas/genética , Ratas , Infecciones Estreptocócicas/virología , Fagos de Streptococcus/genética , Fagos de Streptococcus/metabolismo , Streptococcus mitis/virología , Proteínas Virales/genética , Virulencia
6.
AIDS Rev ; 6(2): 97-106, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15332432

RESUMEN

BACKGROUND: Cardiac complications are becoming more important in patients with HIV infection. The most common is infective endocarditis (IE) in patients who are intravenous drug addicts (IVDA). Other less common problems are pulmonary hypertension, cardiotoxicity, pericardial effusion, cardiac neoplasms, etc. PATIENTS AND METHODS: A literature review of published studies on IE was done and the personal experience of the authors is reflected. RESULTS: The clinical pattern of IE has remained unchanged. It is usually due to Staphylococcus aureus and is more commonly localized to the right side of the heart. It is not clearly defined if HIV infection is responsible for the worst evolution in these patients and the treatment is the same as that used in HIV- subjects. CONCLUSIONS: IE is responsible for 5-20% of hospital admissions and for 5-10% of total deaths in IVDA patients with HIV infection, but the clinical outcome of the patients depends on the affected valve and the culture germen rather than the HIV serostatus.


Asunto(s)
Endocarditis Bacteriana/virología , Infecciones por VIH/complicaciones , VIH-1/crecimiento & desarrollo , Antibacterianos/uso terapéutico , Ecocardiografía , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/terapia , Infecciones por VIH/virología , Humanos , Pronóstico , Infecciones Estafilocócicas/patología , Infecciones Estafilocócicas/terapia , Infecciones Estafilocócicas/virología , Staphylococcus aureus/crecimiento & desarrollo , Abuso de Sustancias por Vía Intravenosa/microbiología , Abuso de Sustancias por Vía Intravenosa/virología
7.
Clin Microbiol Infect ; 9(1): 45-54, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12691542

RESUMEN

OBJECTIVES: To add to the limited information on infective endocarditis (IE) not related to intravenous drug abuse (IVDA) in HIV-1-infected patients. METHODS: We have reviewed the characteristics of eight cases of IE in non-IVDA HIV-1 infected patients diagnosed in our institution between 1979 and 1999 as well as cases in the literature. RESULTS: All our patients were male, and the mean age was 44 years (range 29-64). HIV-1 risk factors were: homosexuality in five, heterosexuality in two, and the use of blood products in one. HIV stage C was found in six cases, and the median (range) CD4 cell count was 22/microL (4-274 cells/microL). IE was caused by Enterococcus faecalis in three cases, staphylococci in two cases, and Salmonella enteritidis, viridans group streptococci and Coxiella burnetii in one case each. Three patients acquired IE while in the hospital. All IE cases involved a native valve, and underlying valve disease was found in three patients. The aortic valve was the most frequently affected (five cases). Two patients underwent surgery, with a good outcome, and one patient died. Fourteen cases of IE not related to IVDA in HIV-1-infected patients were found in the literature review. The most common causative agents were Salmonella spp. and fungi (four cases each). Two patients had prosthetic valve IE, and the mitral valve was the most frequently affected (10 cases). The remaining clinical characteristics and the outcome were similar to those in the present series. CONCLUSIONS: IE not related to IVDA is rare in HIV-1-infected patients. In more than half of the cases, IE develops in patients with advanced HIV-1 disease. A wide etiologic range is found, reflecting different clinical and environmental conditions. None of the patients who underwent surgery died, and the overall mortality rate was not higher than in non-HIV-1-infected patients with IE.


Asunto(s)
Endocarditis Bacteriana/etiología , Infecciones por VIH/complicaciones , VIH-1/crecimiento & desarrollo , Abuso de Sustancias por Vía Intravenosa/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adulto , Recuento de Linfocito CD4 , Endocarditis Bacteriana/patología , Endocarditis Bacteriana/virología , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/patología
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