Levels of Alpha-Toxin Correlate with Distinct Phenotypic Response Profiles of Blood Mononuclear Cells and with agr Background of Community-Associated Staphylococcus aureus Isolates

Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of alpha-toxin than did the proliferative supernatants. Addition of alpha-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, delta-toxin or phenol soluble modulin alpha-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.

Climate response to physiological forcing of carbon dioxide simulated by the coupled Community Atmosphere Model (CAM3.1) and Community Land Model (CLM3.0)

Increasing concentrations of atmospheric CO2 decrease stomatal conductance of plants and thus suppress canopy transpiration. The climate response to this CO2-physiological forcing is investigated using the Community Atmosphere Model version 3.1 coupled to Community Land Model version 3.0. In response to the physiological effect of doubling CO2, simulations show a decrease in canopy transpiration of 8%, a mean warming of 0.1K over the land surface, and negligible changes in the hydrological cycle. These climate responses are much smaller than what were found in previous modeling studies. This is largely a result of unrealistic partitioning of evapotranspiration in our model control simulation with a greatly underestimated contribution from canopy transpiration and overestimated contributions from canopy and soil evaporation. This study highlights the importance of a realistic simulation of the hydrological cycle, especially the individual components of evapotranspiration, in reducing the uncertainty in our estimation of climatic response to CO2-physiological forcing. Citation: Cao, L., G. Bala, K. Caldeira, R. Nemani, and G.Ban-Weiss (2009), Climate response to physiological forcing of carbon dioxide simulated by the coupled Community Atmosphere Model (CAM3.1) and Community Land Model (CLM3.0).

Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia

Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies to endogenous FVIII in individuals with acquired hemophilia. We have described FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in acquired hemophilia patients. Here, we compared the properties of proteolytic auto- and allo-antibodies. Rates of FVIII hydrolysis differed significantly between the two groups of antibodies. Proline-phenylalanine-arginine-methylcoumarinamide was a surrogate substrate for FVIII-hydrolyzing autoantibodies. Our data suggest that populations of proteolytic anti-FVIII IgG in acquired hemophilia patients are different from that of inhibitor-positive hemophilia A patients.