When dealing with organisms, which lack a non-human natural host,

When dealing with organisms, which lack a non-human natural host, we can never be perfectly certain and therefore must rely on additional accumulated supportive (usually indirect) evidence. If our purified His-IFS (NADase inhibitor) is able to rescue STSS patients in future that could provide a more ethically acceptable form of direct evidence.

Conclusions We have presented further supportive evidence that NADase is important for severe invasive disease of S. pyogenes in vivo using the experimental mouse model. Furthermore, we provided useful evidence that the MLN8237 NADase is the potential target to suppress the virulence. Acknowledgements We thank Laura Leverton for critical reading of the manuscript and Hideki Matsui and Takayuki Ichikawa for technical assistance. This study was supported by Grant numbers 19590452 and LY2874455 datasheet 21790425 from the Ministry of Education, Science and Culture of the Japanese government. M. I. was supported by a grant for Research on Publicly Essential Drugs and Medical Devices, No.KHC1021 from the Japan Health Sciences Foundation. References 1. Cone LA, Woodard DR, Schlievert PM, Tomory GS: Clinical and bacteriologic

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