Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes

Abstract: The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins

A computational and experimental investigation of turbulent jet and crossflow interaction

The flowfield induced by a single circular jet exhausting perpendicularly from a flat plate into a crossflow has been investigated numerically. The flow regime investigated corresponds to that encountered in a modern gas-turbine combustor. Reynolds-averaged solutions were obtained using a pressure-based Navier-Stokes solver. The standard k - ε turbulence model with and without nonequilibrium modification was employed. Two different momentum flux ratios, J, between the jet and the free stream are investigated, namely, J = 34.2 and J = 42.2. To aid the evaluation of the computational capability, experimental information also has been obtained, including mean and root-mean-square (RMS) velocity distributions downstream of the jet, and the detailed velocity profile at the jet exit. An evaluation of the different convection schemes reveals that the second-order upwind scheme does a noticeably better job than the first-order scheme to predict the velocity profile at the jet exit while predicting less mixing than the experimental measurement during the jet and free stream interaction. It appears that turbulence modeling primarily is responsible for the deficiency the accounting for the physics of the jet and free stream interaction