Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection

Wei Jiun Tsai, Yi Hsin Lai, Yong An Shi, Michal Hammel, Anthony P. Duff, Andrew E. Whitten, Karyn L. Wilde, Chun Ming Wu, Robert Knott, U. Ser Jeng, Chia Yu Kang, Chih Yu Hsu, Jian Li Wu, Pei Jane Tsai, Chuan Chiang-Ni, Jiunn Jong Wu, Yee Shin Lin, Ching Chuan Liu, Toshiya Senda, Shuying Wang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection.

Original languageEnglish
Article number124
JournalCommunications Biology
Issue number1
Publication statusPublished - 2023 Jan 31

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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