Multiple Domains of Staphylococcal Superantigen-like Protein 11 (SSL11) Contribute to Neutrophil Inhibition. Biochemistry 2022 Apr 05;61(7):616-624
Date
03/15/2022Pubmed ID
35285627Pubmed Central ID
PMC9817067DOI
10.1021/acs.biochem.2c00018Scopus ID
2-s2.0-85127145605 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
Staphylococcus aureus is an opportunistic pathogen producing many immune evasion molecules targeting various components of the host immune defense, including the Staphylococcal superantigen-like protein (SSL 1-14) family. Despite sharing similar structures with the powerful superantigens (SAgs), which cause massive T cell activation, SSLs interfere with a wide range of innate immune defenses. SSLs are divided into two subgroups, SSLs that contain a conserved carbohydrate Sialyl Lewis X [Neu5Acα2-3Galβ1-4(Fucα1-3) GlcNAcβ, SLeX] binding site and SSLs that lack the SLeX binding site. SSL2-6 and SSL11 possess the SLeX binding site. Our previous studies showed that SSL11 arrests cell motility by inducing cell adhesion in differentiated HL60 (dHL60) cells, while SSL7 did not bind dHL60 cells. SSL7-based chimeras were engineered by exchanging the SSL7 sequence with the corresponding SSL11 sequence and assaying for a gain of SSL11 function, namely, the induction of cell spreading and motility arrest. In addition to the SLeX-binding site, we observed that three beta-strands β6, β7, and β9 and the N-terminal residues, Y16 and Y17, transitioned SSL7 to gain SSL11 activities. These studies define the structure-function properties of SSL11 that may allow SSL11 to inhibit S. aureus clearance by the host innate immune system, allowing S. aureus to maintain a carrier state in humans, an understudied aspect of S. aureus pathogenesis.
Author List
Yang C, Barbieri JT, Dahms NM, Chen CAuthors
Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinNancy M. Dahms PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Bacterial ProteinsHumans
Neutrophils
Protein Binding
Staphylococcal Infections
Staphylococcus aureus
Superantigens
