title: NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates.
abstract: BACKGROUND
  NAD-glycohydrolase (NADase) secreted by M-1 group A streptococcal (GAS) isolates are suspected as one of the virulence factors to cause severe invasive disease including streptococcal toxic shock-like syndrome (STSS). M-1 GAS strains were divided into three groups based on NADase activity: high activity, low activity and no activity in our previous report.
  
  
  RESULTS
  The representative high activity isolates taken from STSS patients showed higher virulence compared with isolates from the low activity group, when used to infect mice. The knockout mutant of the nga gene, which encodes NADase also showed reduced virulence in a mouse infection study. The cloned nga gene was able to significantly complement the lost virulence. In addition, the solution containing purified recombinant IFS, which is an inhibitor of NADase, partially rescued mice infected with S. pyogenes.
  
  
  CONCLUSIONS
  These results indicate that NADase is important for the virulence of S. pyogenes in vivo and is the potential target to suppress the virulence.
authors.affiliation: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-cho Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.forename: Masanori
authors.initials: M
authors.lastname: Isaka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Minami
authors.forename: Tadao
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D051379:Mice; D008813:Mice, Inbred ICR; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors* / Q000235:genetics; D013290:Streptococcal Infections / Q000382:microbiology* / Q000473:pathology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D009244:NAD+ Nucleosidase
references.citation: Cell Microbiol. 2009 Jan;11(1):1-12
references.pmid: 18710460
references.citation: Infect Immun. 2005 Oct;73(10):6562-6
references.pmid: 16177331
references.citation: J Infect Dis. 2000 Oct;182(4):1117-28
references.pmid: 10979908
references.citation: J Biol Chem. 2006 Apr 7;281(14):9181-9
references.pmid: 16380378
references.citation: Mol Microbiol. 2002 Apr;44(1):257-69
references.pmid: 11967084
references.citation: PLoS Pathog. 2005 Dec;1(4):e35
references.pmid: 16333395
references.citation: Gene. 1996 Oct 24;177(1-2):137-47
references.pmid: 8921859
references.citation: J Clin Invest. 1998 Aug 1;102(3):550-60
references.pmid: 9691092
references.citation: J Biol Chem. 1998 Nov 13;273(46):30110-5
references.pmid: 9804765
references.citation: Cell. 2001 Jan 12;104(1):143-52
references.pmid: 11163247
references.citation: Lancet. 1990 Nov 10;336(8724):1167-71
references.pmid: 1978035
references.citation: J Clin Microbiol. 2002 Jul;40(7):2642-4
references.pmid: 12089296
references.citation: Pediatr Infect Dis J. 1994 Jun;13(6):561-6
references.pmid: 8078755
references.citation: J Infect Dis. 2005 Sep 1;192(5):771-82
references.pmid: 16088826
references.citation: J Biol Chem. 2006 Mar 24;281(12):8216-23
references.pmid: 16431917
references.citation: FEMS Microbiol Lett. 2000 Oct 15;191(2):235-41
references.pmid: 11024269
references.citation: Microbes Infect. 2004 Oct;6(12):1073-7
references.pmid: 15380776
references.citation: Infect Immun. 2000 Feb;68(2):535-42
references.pmid: 10639414
references.citation: J Bacteriol. 1996 Sep;178(18):5546-9
references.pmid: 8808951
references.citation: N Engl J Med. 1987 Jul 16;317(3):146-9
references.pmid: 3299086
references.citation: JAMA. 1993 Jan 20;269(3):384-9
references.pmid: 8418346
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4658-63
references.pmid: 11296296
references.citation: Microbiology (Reading). 1998 Nov;144 ( Pt 11):3079-3086
references.pmid: 9846743
references.citation: N Engl J Med. 1989 Jul 6;321(1):1-7
references.pmid: 2659990
references.citation: Microbiology (Reading). 2007 Dec;153(Pt 12):4253-4260
references.pmid: 18048938