A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins

Author:

D’Gama Jonathan D.12,Ma Zhe2345,Zhang Hailong12,Liu Xu12,Fan Hongjie345ORCID,Morris Ellen Ruth A.6,Cohen Noah D.6ORCID,Cywes-Bentley Colette12,Pier Gerald B.12,Waldor Matthew K.127

Affiliation:

1. Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA

2. Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts, USA

3. MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China

4. Ministry of Agriculture Key Laboratory of Animal Bacteriology, Nanjing, Jiangsu, China

5. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China

6. Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, USA

7. Howard Hughes Medical Institute, Boston, Massachusetts, USA

Abstract

M proteins are surface-anchored virulence factors in group A streptococci, human pathogens. Here, we identified an M-like protein, SzM, and its positive regulator, SezV, in Streptococcus equi subspecies zooepidemicus (SEZ), an important group of pathogens for domesticated animals, including horses and pigs. SzM and SezV homologues were found in the genomes of all SEZ and S. equi subspecies equi and M18 group A streptococcal strains analyzed but not in other streptococci. Mutant SEZ strains lacking either sezV or szM were highly attenuated in a mouse model of infection. Collectively, our findings suggest that SezV-related regulators and the linked SzM family of M-like proteins define a new subset of virulent streptococci.

Funder

Young Backbone Teachers Study Abroad Program of China Scholarship Council

National Key Research and Development Program

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

Howard Hughes Medical Institute

National Natural Science Foundation of China

Priority Academic Program Development of Jiangsu Higher Education Institutions

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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