Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion
Igor H. Wierzbicki,
Anaamika Campeau,
Diana Dehaini,
Maya Holay,
Xiaoli Wei,
Trever Greene,
Man Ying,
Jenna S. Sands,
Anne Lamsa,
Elina Zuniga,
Kit Pogliano,
Ronnie H. Fang,
Christopher N. LaRock,
Liangfang Zhang,
David J. Gonzalez
Affiliations
Igor H. Wierzbicki
Department of Pharmacology and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA
Anaamika Campeau
Department of Pharmacology and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA
Diana Dehaini
Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA
Maya Holay
Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA
Xiaoli Wei
Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA
Trever Greene
Department of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA
Man Ying
Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA
Jenna S. Sands
Department of Microbiology and Immunology, Division of Infectious Diseases, and Antimicrobial Resistance Center, Emory University, Atlanta, GA 30322, USA
Anne Lamsa
Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA
Elina Zuniga
Department of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA
Kit Pogliano
Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA
Ronnie H. Fang
Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA
Christopher N. LaRock
Department of Microbiology and Immunology, Division of Infectious Diseases, and Antimicrobial Resistance Center, Emory University, Atlanta, GA 30322, USA
Liangfang Zhang
Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093, USA
David J. Gonzalez
Department of Pharmacology and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding author
Summary: Group A Streptococcus (GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function—annotated subsequently as S protein—in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory. : Wierzbicki et al. show that S protein is a major group A Streptococcus (GAS) virulence factor that facilitates bacterial coating with lysed red blood cells to promote molecular mimicry, which increases virulence in vitro and in vivo. Removal of S protein reduces the abundance of multiple virulence factors and attenuates virulence. Keywords: Biomimetic Virulomics, S. pyogenes, group A Streptococcus, S protein, SPy_0802, virulence, systemic infection, multiplexed proteomics, tandem mass tags
