Molecular Epidemiology of nga and NAD Glycohydrolase/ADP-Ribosyltransferase Activity among Streptococcus pyogenes Causing Streptococcal Toxic Shock Syndrome

• Published in: The Journal of infectious diseases Vol. 182; no. 4; pp. 1117 - 1128
• Main Authors: Stevens, Dennis L., Salmi, Daniel B., McIndoo, Eric R., Bryant, Amy E.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.10.2000; University of Chicago Press; Oxford University Press
• Subjects: Actins; ADP-ribosyltransferase; Amino Acid Sequence; Amino acids; Bacterial diseases; Base Sequence; Biological and medical sciences; Chemiluminescence; Chemotaxis, Leukocyte; Chromosome Mapping; Chromosomes, Bacterial; Genomes; Human bacterial diseases; Humans; Infections; Infectious diseases; Major Articles; Medical sciences; Molecular Epidemiology; Molecular Sequence Data; NAD+ Nucleosidase - chemistry; NAD+ Nucleosidase - genetics; NAD+ Nucleosidase - metabolism; nga gene; Plasmids; Polymerase Chain Reaction; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Sequence Alignment; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Serotyping; Shock, Septic - microbiology; Staphylococcal infections, streptococcal infections, pneumococcal infections; Streptococcal Infections - epidemiology; Streptococcus; Streptococcus pyogenes; Streptococcus pyogenes - classification; Streptococcus pyogenes - enzymology; Streptococcus pyogenes - genetics; Streptococcus pyogenes - pathogenicity; Toxins; Virulence; United States; North America; America; Human; nucleosidase; Enzyme; Infection; NAD; Streptococcaceae; Strecptococcal toxic shock syndrome; Glycosidases; Streptococcal infection; Streptococcus A; Bacteriosis; Molecular epidemiology; Bacteria; Hydrolases; Micrococcales; N-Glycosidases; Streptococcus pyogenes
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315850

Severe invasive group A streptococcal (GAS) infections emerged in the late 1980s, yet no single virulence factor has been common to all isolates from infected patients. A strong association was recently found between isolates of such cases (regardless of M type) and the production of NAD glycohydrolase (NADase). Of interest, all M-1 strains isolated after 1988 were positive for NADase, whereas virtually all M-1 GAS were previously negative for NADase. Genetic analysis demonstrated that GAS isolates were >96% identical in nga and 199% identical in their upstream regulatory sequences. Furthermore, because NADase-negative strains did not produce immunoreactive NADase, we concluded that additional regulatory element(s) control NADase production. NADase purified from GAS altered neutrophil-directed migration and chemiluminescence responses and had potent ADP-ribosyltransferase activity. In summary, the temporal relationship of NADase expression, alone or with other streptococcal virulence factors, may contribute to the pathogenesis of invasive GAS infections.