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11-14 June 2023
Lund
Europe/Stockholm timezone

Structural insight into the synergistic activities of NADase and SLO in the pathogenesis of Group A Streptococcus infection

Not scheduled
20m
Palaestra et Odeum & AF Borgen (Lund)

Palaestra et Odeum & AF Borgen

Lund

Sweden
Poster

Speaker

Prof. Shu-Ying Wang (Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan)

Description

Group A Streptococcus (GAS) is a strict human pathogen renowned for its highly aggressive destruction of host tissues that can lead to life-threatening diseases including streptococcal toxic shock syndrome and necrotizing fasciitis. GAS possesses a unique pathogenic trait to enhance its virulence by utilizing the synergism of two secreted toxins, Streptolysin O (SLO) and NAD+-glycohydrolase (NADase). How NADase and SLO assemble into a complex to synergistically promote intracellular survival and resistance to innate immunity within human cells is a long-standing question. By combining X-ray crystallography and small-angle X-ray scattering (SAXS), we decipher the first structure of NADase/SLO complex and reveal the dynamic nature of the complex in solution. The functionally-relevant conformations of the NADase/SLO complex revealed by SAXS suggest the dynamic interplay between SLO and NADase is fundamental to the functioning of the complex. Moreover, the introduction of a complex-disruptive mutation in GAS genome results in decreased resistance to phagocytic killing in vitro. Furthermore, mice infected with GAS mutant harboring the disruptive mutation displayed reduced skin lesions. 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.

Primary author

Prof. Shu-Ying Wang (Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan)

Co-authors

Mrs Wei-Jiunn Tsai (Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan) Dr Michal Hammel (Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA) Dr U-Ser Jeng (National Synchrotron Radiation Research Center, Hsinchu Science Park, Hsinchu, Taiwan)

Presentation Materials

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