NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates.
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.
Tatsuno
Ichiro
I
Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-cho Mizuho-ku, Nagoya 467-8601, Japan.
Isaka
Masanori
M
Minami
Masaaki
M
Hasegawa
Tadao
T
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
D001426:Bacterial Proteins; D037521:Virulence Factors; D009244:NAD+ Nucleosidase
Cell Microbiol. 2009 Jan;11(1):1-12
18710460
Infect Immun. 2005 Oct;73(10):6562-6
16177331
J Infect Dis. 2000 Oct;182(4):1117-28
10979908
J Biol Chem. 2006 Apr 7;281(14):9181-9
16380378
Mol Microbiol. 2002 Apr;44(1):257-69
11967084
PLoS Pathog. 2005 Dec;1(4):e35
16333395
Gene. 1996 Oct 24;177(1-2):137-47
8921859
J Clin Invest. 1998 Aug 1;102(3):550-60
9691092
J Biol Chem. 1998 Nov 13;273(46):30110-5
9804765
Cell. 2001 Jan 12;104(1):143-52
11163247
Lancet. 1990 Nov 10;336(8724):1167-71
1978035
J Clin Microbiol. 2002 Jul;40(7):2642-4
12089296
Pediatr Infect Dis J. 1994 Jun;13(6):561-6
8078755
J Infect Dis. 2005 Sep 1;192(5):771-82
16088826
J Biol Chem. 2006 Mar 24;281(12):8216-23
16431917
FEMS Microbiol Lett. 2000 Oct 15;191(2):235-41
11024269
Microbes Infect. 2004 Oct;6(12):1073-7
15380776
Infect Immun. 2000 Feb;68(2):535-42
10639414
J Bacteriol. 1996 Sep;178(18):5546-9
8808951
N Engl J Med. 1987 Jul 16;317(3):146-9
3299086
JAMA. 1993 Jan 20;269(3):384-9
8418346
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4658-63
11296296
Microbiology (Reading). 1998 Nov;144 ( Pt 11):3079-3086
9846743
N Engl J Med. 1989 Jul 6;321(1):1-7
2659990
Microbiology (Reading). 2007 Dec;153(Pt 12):4253-4260
18048938