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

doi:10.1038/s42003-023-04502-0

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^*

^*Corresponding author for this work

Department of Biotechnology and Laboratory Science in Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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 language	English
Article number	124
Journal	Communications Biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-04502-0
State	Published - Dec 2023

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Tsai, W. J., Lai, Y. H., Shi, Y. A., Hammel, M., Duff, A. P., Whitten, A. E., Wilde, K. L., Wu, C. M., Knott, R., Jeng, U. S., Kang, C. Y., Hsu, C. Y., Wu, J. L., Tsai, P. J., Chiang-Ni, C., Wu, J. J., Lin, Y. S., Liu, C. C., Senda, T., & Wang, S. (2023). Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection. Communications Biology, 6(1), Article 124. https://doi.org/10.1038/s42003-023-04502-0

@article{705ce868538946be8606d6d7b46e1f51,

title = "Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection",

abstract = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s42003-023-04502-0",

language = "English",

volume = "6",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Tsai, WJ, Lai, YH, Shi, YA, Hammel, M, Duff, AP, Whitten, AE, Wilde, KL, Wu, CM, Knott, R, Jeng, US, Kang, CY, Hsu, CY, Wu, JL, Tsai, PJ, Chiang-Ni, C, Wu, JJ, Lin, YS, Liu, CC, Senda, T & Wang, S 2023, 'Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection', Communications Biology, vol. 6, no. 1, 124. https://doi.org/10.1038/s42003-023-04502-0

TY - JOUR

T1 - Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection

AU - Tsai, Wei Jiun

AU - Lai, Yi Hsin

AU - Shi, Yong An

AU - Hammel, Michal

AU - Duff, Anthony P.

AU - Whitten, Andrew E.

AU - Wilde, Karyn L.

AU - Wu, Chun Ming

AU - Knott, Robert

AU - Jeng, U. Ser

AU - Kang, Chia Yu

AU - Hsu, Chih Yu

AU - Wu, Jian Li

AU - Tsai, Pei Jane

AU - Chiang-Ni, Chuan

AU - Wu, Jiunn Jong

AU - Lin, Yee Shin

AU - Liu, Ching Chuan

AU - Senda, Toshiya

AU - Wang, Shuying

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85147106545&partnerID=8YFLogxK

U2 - 10.1038/s42003-023-04502-0

DO - 10.1038/s42003-023-04502-0

M3 - Article

C2 - 36721030

AN - SCOPUS:85147106545

SN - 2399-3642

VL - 6

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 124

ER -

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

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