A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase

PLoS Pathogens

Patricia J Anderson¹  Michael G Caparon²  Michael A Meehl²  Jerome S Pinkner²  Scott J Hultgren³ 

[1] Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America;Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America;Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Streptococcus pyogenes;    Protein extraction;    Toxins;    Expressed sequence tags;    Plasmid construction;    Streptococcus;    Host cells;    Pathogenesis;   

DOI  :  10.1371/journal.ppat.0010035

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The Streptococcus pyogenes NAD-glycohydrolase (SPN) is a toxic enzyme that is introduced into infected host cells by the cytolysin-mediated translocation pathway. However, how S. pyogenes protects itself from the self-toxicity of SPN had been unknown. In this report, we describe immunity factor for SPN (IFS), a novel endogenous inhibitor that is essential for SPN expression. A small protein of 161 amino acids, IFS is localized in the bacterial cytoplasmic compartment. IFS forms a stable complex with SPN at a 1:1 molar ratio and inhibits SPN's NAD-glycohydrolase activity by acting as a competitive inhibitor of its β-NAD+ substrate. Mutational studies revealed that the gene for IFS is essential for viability in those S. pyogenes strains that express an NAD-glycohydrolase activity. However, numerous strains contain a truncated allele of ifs that is linked to an NAD-glycohydrolase−deficient variant allele of spn. Of practical concern, IFS allowed the normally toxic SPN to be produced in the heterologous host Escherichia coli to facilitate its purification. To our knowledge, IFS is the first molecularly characterized endogenous inhibitor of a bacterial β-NAD+−consuming toxin and may contribute protective functions in the streptococci to afford SPN-mediated pathogenesis.

【 授权许可】

CC BY