Generation of a Convalescent Model of Virulent Francisella tularensis Infection for Assessment of Host Requirements for Survival of Tularemia

Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR+ cells, γδTCR+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4+ and CD8+ cells are the primary producers of IFN-γand that γδTCR+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

Oral nystatin prophylaxis to prevent invasive candidiasis in neonatal intensive care unit

The use of oral nystatin to prevent fungal colonisation and infection in neonates in the Neonatal Intensive Care Unit (NICU) is still an open question and not yet recommended as a standard of care. To determine whether prophylactic oral nystatin results in a decreased incidence of invasive candidiasis in the newborn infants, a total of 3991 infants were divided randomly into two groups. Group A infants (n = 1995), only those neonates who were identified as yeast carriers (oral moniliasis) were treated with oral nystatin. Group B infants, all neonates who were admitted to the unit received oral nystatin, was routinely administered three times a day. Group A was divided into groups A1 and A2 (who were treated only if identified as yeast carriers). Urine and rectal cultures were taken on admission and then weekly thereafter. There were 215 (14.2%), 27 (5.6%) and 36 (1.8%) patients positive for invasive candidiasis in groups A1, A2 and B respectively. Oral nystatin prophylaxis significantly reduced the invasive candidiasis (P = 0.004) in extremely low-birth weight (ELBW) and very low-birth weight (VLBW) infants. Prophylactic administration of oral nystatine to the ELBW and VLBW infants results in a decreased risk of invasive candidiasis

Simultaneous quantification of protein order and disorder

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