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Streptococcal collagen‐like protein A and general stress protein 24 are immunomodulating virulence factors of group A Streptococcus
Author(s) -
Tsatsaronis James A.,
Hollands Andrew,
Cole Jason N.,
Maamary Peter G.,
Gillen Christine M.,
Ben Zakour Nouri L.,
Kotb Malak,
Nizet Victor,
Beatson Scott A,
Walker Mark J.,
SandersonSmith Martina L.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-226662
Subject(s) - virulence , biology , streptococcus , microbiology and biotechnology , streptococcus pyogenes , serotype , mutant , group a , pathogen , operon , genetics , bacteria , gene , medicine , staphylococcus aureus
In Western countries, invasive infections caused by M1T1 serotype group A Streptococcus (GAS) are epidemiologically linked to mutations in the control of virulence regulatory 2‐component operon ( covRS ). In indigenous communities and developing countries, severe GAS disease is associated with genetically diverse non‐M1T1 GAS serotypes. Hypervirulent M1T1 covRS mutant strains arise through selection by human polymorphonuclear cells for increased expression of GAS virulence factors such as the DNase Sda1, which promotes neutrophil resistance. The GAS bacteremia isolate NS88.2 ( emm 98.1) is a covS mutant that exhibits a hypervirulent phenotype and neutrophil resistance yet lacks the phage‐encoded Sda1. Here, we have employed a comprehensive systems biology (genomic, transcriptomic, and proteomic) approach to identify NS88.2 virulence determinants that enhance neutrophil resistance in the non‐M1T1 GAS genetic background. Using this approach, we have identified streptococcal collagen‐like protein A and general stress protein 24 proteins as NS88.2 determinants that contribute to survival in whole blood and neutrophil resistance in non‐M1T1 GAS. This study has revealed new factors that contribute to GAS pathogenicity that may play important roles in resisting innate immune defenses and the development of human invasive infections—Tsatsaronis, J. A., Hollands, A., Cole, J. N., Maamary, P. G., Gillen, C. M., Ben Zakour, N. L., Kotb, M., Nizet, V., Beatson, S. A. Walker, M. J., Sanderson‐Smith, M. L. Streptococcal collagen‐like protein A and general stress protein 24 are immunomodulating virulence factors of group A Streptococcus. FASEB J. 27, 2633‐2643 (2013). www.fasebj.org