Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes

Xinyu Zhou; Yuling Zheng; Qingyu Lv; Decong Kong; Bin Ji; Xuelian Han; Dongsheng Zhou; Zeyu Sun; Li Zhu; Peng Liu; Hua Jiang; Yongqiang Jiang

doi:10.1080/21505594.2021.1928395

Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes

Virulence. 2021 Dec;12(1):1418-1437. doi: 10.1080/21505594.2021.1928395.

Authors

Xinyu Zhou¹, Yuling Zheng¹, Qingyu Lv¹, Decong Kong¹, Bin Ji², Xuelian Han¹, Dongsheng Zhou¹, Zeyu Sun¹, Li Zhu³, Peng Liu¹, Hua Jiang¹, Yongqiang Jiang¹

Affiliations

¹ State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, China.
² Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.
³ Beijing Institute of Biotechnology, Beijing, China.

Abstract

The community-associated Methicillin-resistant Staphylococcus aureus strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many S. aureus strains. In addition, δ-toxin exists in the S. aureus culture supernatant as both N-terminus formylated δ-toxin (fδ-toxin) and deformylated δ-toxin (dfδ-toxin) groups. Although δ-toxin has been studied for more than 70 years, its functions remain unclear. We isolated and purified PSMs from the supernatant of S. aureus MW2, and found fibrils and oligomers aggregates by Size Exclusion Chromatography. After analyzing PSM aggregates and using peptide simulations, we found that the difference in the monomer structure of fδ-toxin and dfδ-toxin might ultimately lead to differences in the aggregation ability: fδ-toxin and dfδ-toxin tend to form fibrils and oligomers respectively. Of note, we found that fδ-toxin fibrils enhanced the stability of biofilms, while dfδ-toxin oligomers promoted their dispersal. Additionally, oligomeric dfδ-toxin combined with PSMα to form a complex with enhanced functionality. Due to the different aggregation capabilities and functions of fδ-toxin and dfδ-toxin, we speculate that they may be involved in the regulation of physiological activities of S. aureus. Moreover, the dfδ-toxin oligomer not only provides a new form of complex in the study of PSMα, but also has significance as a reference in oligomer research pertaining to some human amyloid diseases.

Keywords: CA-MRSA; PSMα; Staphylococcus aureus; amyloid fibrils; complex; deformylation; formylation; oligomer; δ-toxin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid / chemistry*
Bacterial Toxins / chemistry*
Biofilms
Staphylococcus aureus*
Virulence

Substances

Amyloid
Bacterial Toxins
staphylococcal delta toxin

Grants and funding

This work was supported by the National Natural Science Foundation of China (81772144, 82002115, 82002116), the Chinese State Key Project Specialized for Infectious Diseases (2018ZX10711001-003, 2018ZX10712001-015, 2018ZX10732401-001-008) and the State Key Laboratory of Pathogen and Biosecurity (SKLPBS1816) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.