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7. The VraSR regulatory system contributes to virulence in Streptococcus suisvia resistance to innate immune defenses

Author

Chang, Peixi, Li, Weitian, Shi, Guolin, Li, Huan, Yang, Xiaoqing, Xia, Zechen, Ren, Yuan, Li, Zhiwei, Chen, Huanchun, and Bei, Weicheng

Abstract

ABSTRACTStreptococcus suisis a highly invasive pathogen that can cause sepsis and meningitis in pigs and humans. However, we have limited understanding of the mechanisms S. suisuses to evade innate immunity. To investigate the involvement of the two-component signal transduction system of S. suisin host immune defense, we examined the expression of 15 response regulators of S. suisfollowing stimulation with polymorphonuclear leukocytes (PMNs). We found that several response regulators were significantly up-regulated including vraR. Thus, we constructed an isogenic deletion mutant of vraSRgenes in S. suisand demonstrated VraSR promotes both bacterial survival in human blood and resistance to human PMN-mediated killing. The VraSR mutant was more susceptible to phagocytosis by human PMNs and had greater sensitivity to oxidant and lysozyme than wild-type S. suis. Furthermore, in vitrofindings and in vivoevidence from a mouse infection model together strongly demonstrate that ΔvraSRhad greatly attenuated virulence compared with wild-type S. suis. Collectively, our data reveal that VraSR is a critical regulatory system that contributes to the survival of S. suisand its ability to defend against host innate immunity.

Published
2018
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