RESUMEN
Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis but has been recently isolated from non-pregnant adults with underlying medical conditions like diabetes. Despite diabetes being a key risk factor for invasive disease, the pathological consequences during GBS infection remain poorly characterized. Here, we demonstrate the pathogenicity of the GBS90356-ST17 and COH1-ST17 strains in streptozotocin-induced diabetic mice. We show that GBS can spread through the bloodstream and colonize several tissues, presenting a higher bacterial count in diabetic-infected mice when compared to non-diabetic-infected mice. Histological sections of the lungs showed inflammatory cell infiltration, collapsed septa, and red blood cell extravasation in the diabetic-infected group. A significant increase in collagen deposition and elastic fibers were also observed in the lungs. Moreover, the diabetic group presented red blood cells that adhered to the valve wall and disorganized cardiac muscle fibers. An increased expression of KC protein, IL-1ß, genes encoding immune cell markers, and ROS (reactive oxygen species) production was observed in diabetic-infected mice, suggesting GBS promotes high levels of inflammation when compared to non-diabetic animals. Our data indicate that efforts to reverse the epidemic of diabetes could considerably reduce the incidence of invasive infection, morbidity and mortality due to GBS.
RESUMEN
This chapter presents the methodology to carry out infection of humanized plasminogen mice with Group A Streptococcus (GAS). This model of invasive disease has been widely used within the field to study the virulence of different GAS strains, host-pathogen interactions, the importance of particular virulence factors, and preclinical evaluation of novel treatments and vaccines. The model has shown to be highly reproducible and therefore represents an invaluable tool for GAS research.
Asunto(s)
Modelos Animales de Enfermedad , Plasminógeno/metabolismo , Infecciones Estreptocócicas/inmunología , Animales , Antígenos Bacterianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Interacciones Huésped-Patógeno , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Unión Proteica , Streptococcus pyogenes/metabolismo , Virulencia , Factores de Virulencia/metabolismoRESUMEN
Pneumonia-induced sepsis is responsible for about 50% of cases in the world. Patients who develop severe sepsis and septic shock present organ dysfunction and elevated plasma cytokine levels, which may lead to death. Clinical scores are important to evaluate the framework of septic patients and are used to predict the syndrome progress, prognostics, and mortality. The objective of the present study was to verify the applicability of a murine clinical score system to experimental sepsis (pneumonia-induced sepsis in male mice) and to correlate it with mortality and bacterial dissemination in different organs. Results demonstrated that animals which present higher clinical scores (>3) are more likely to die. Animals presenting high clinical scores exhibited transient bacteremia and displayed bacterial spreading to different organs such as heart, kidney, liver, and brain. There is a correlation between clinical score and bacterial dissemination and consequently greater risk of death. In addition, animals which showed bacterial dissemination in more than three organs and high clinical scores presented high levels of cytokines (TNF-α, MCP-1, IL-6, and IL-10) in plasma, lung, heart, liver, kidney, and brain. Therefore, our study suggests that (1) severity scores have predictive power in experimental models of sepsis and (2) high concentrations of tissue cytokines may contribute to localized inflammation and be one of the factors responsible for the systemic inflammatory syndrome of sepsis.