The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus

Chen，Feifei1,2,3; Di，Hongxia2,4; Wang，Yanhui2,4; Peng，Chao5; Chen，Rongrong3,4; Pan，Huiwen3,4; Yang，Cai Guang2,3,4; Liang，Haihua1,6; Lan，Lefu1,2,3,4

2023-12-01

10.1080/21505594.2023.2171641

Virulence   Impact Factor & Quartile

2150-5594

2150-5608

In many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro. We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate. Both Stk1 and AcP-mediated phosphorylation inhibited the enzyme activity of SrtA in vitro. Consequently, deletion of gene (i.e. stp1) encoding serine/threonine phosphatase Stp1, the corresponding phosphatase of Stk1, caused an increase in the phosphorylation level of SrtA. The stp1 deletion mutant mimicked the phenotypic traits of srtA deletion mutant (i.e. attenuated growth where either haemoglobin or haem as a sole iron source and reduced liver infections in a mouse model of systemic infection). Importantly, the phenotypic defects of the stp1 deletion mutant can be alleviated by overexpressing srtA. Taken together, our finding suggests that phosphorylation plays an important role in modulating the activity of SrtA in S. aureus.

protein phosphorylation Sortase A Staphylococcus aureus virulence

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English

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National Natural Science Foundation of China["31870127","32270184"] ; Science and Technology Commission of Shanghai Municipality[19JC1416400] ; State Key Laboratory of Drug Research["SIMM2205KF-07","SIMM2003ZZ-03"]

Immunology ; Infectious Diseases ; Microbiology

Immunology ; Infectious Diseases ; Microbiology

WOS:000931939300001

TAYLOR & FRANCIS INC

2-s2.0-85147895163

Scopus

1.College of Life Science,Northwest University,Xi'an,China
2.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,China
3.Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou,China
4.University of Chinese Academy of Sciences,China
5.National Facility for Protein Science in Shanghai,Zhangjiang Lab,Shanghai Advanced Research Institute,Chinese Academy of Science,China
6.School of Medicine,Southern University of Science and Technology,Shenzhen,China

Chen，Feifei,Di，Hongxia,Wang，Yanhui,et al. The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus[J]. Virulence,2023,14(1).

Chen，Feifei.,Di，Hongxia.,Wang，Yanhui.,Peng，Chao.,Chen，Rongrong.,...&Lan，Lefu.(2023).The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus.Virulence,14(1).

Chen，Feifei,et al."The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus".Virulence 14.1(2023).