Highly Frequent Mutations in Negative Regulators of Multiple Virulence Genes in Group A Streptococcal Toxic Shock Syndrome Isolates

PLoS Pathogens

Tadayoshi Ikebe¹  Haruo Watanabe¹  Takayuki Matsumura²  Manabu Ato²  Kazuo Kobayashi²  Hideki Hasegawa³  Tetsutaro Sata³ 

[1] Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan;Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan;Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan

关键词: Blood;    Neutrophils;    Pharyngitis;    Mutation;    Point mutation;    Mouse models;    Soft tissues;    Streptococcus pyogenes;   

DOI  :  10.1371/journal.ppat.1000832

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock and multiorgan failure; it has a high mortality rate. Although a number of studies have attempted to determine the crucial factors behind the onset of STSS, the responsible genes in group A Streptococcus have not been clarified. We previously reported that mutations of csrS/csrR genes, a two-component negative regulator system for multiple virulence genes of Streptococcus pyogenes, are found among the isolates from STSS patients. In the present study, mutations of another negative regulator, rgg, were also found in clinical isolates of STSS patients. The rgg mutants from STSS clinical isolates enhanced lethality and impaired various organs in the mouse models, similar to the csrS mutants, and precluded their being killed by human neutrophils, mainly due to an overproduction of SLO. When we assessed the mutation frequency of csrS, csrR, and rgg genes among S. pyogenes isolates from STSS (164 isolates) and non-invasive infections (59 isolates), 57.3% of the STSS isolates had mutations of one or more genes among three genes, while isolates from patients with non-invasive disease had significantly fewer mutations in these genes (1.7%). The results of the present study suggest that mutations in the negative regulators csrS/csrR and rgg of S. pyogenes are crucial factors in the pathogenesis of STSS, as they lead to the overproduction of multiple virulence factors.

【 授权许可】

CC BY