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

English version České info

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.

Vyšlo v časopise: Highly Frequent Mutations in Negative Regulators of Multiple Virulence Genes in Group A Streptococcal Toxic Shock Syndrome Isolates. PLoS Pathog 6(4): e32767. doi:10.1371/journal.ppat.1000832
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000832

Souhrn

Zdroje

1. BisnoAL

StevensDL

1996 Streptococcal infections of skin and soft tissues. N Engl J Med 334 240 245

2. AtoM

IkebeT

KawabataH

TakemoriT

WatanabeH

2008 Incompetence of neutrophils to invasive group A streptococcus is attributed to induction of plural virulence factors by dysfunction of a regulator. PLoS ONE 3 e3455 doi:10.1371/journal.pone.0003455

3. Walker MJ

HollandsA

Sanderson-SmithML

ColeJN

KirkJK

2007 DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. Nat Med 13 981 985

4. SumbyP

WhitneyAR

GravissEA

DeLeoFR

MusserJM

2006 Genome-wide analysis of group a streptococci reveals a mutation that modulates global phenotype and disease specificity. PLoS Pathog 2 e5 doi:10.1371/journal.ppat.0020005

5. Miyoshi-AkiyamaT

IkebeT

WatanabeH

UchiyamaT

KirikaeT

2006 Use of DNA arrays to identify a mutation in the negative regulator, csrR, responsible for the high virulence of a naturally occurring type M3 group A streptococcus clinical isolate. J Infect Dis 193 1677 1684

6. BeresSB

SylvaGL

BarbianKD

LeiB

HoffJS

2002 Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proc Natl Acad Sci USA 99 10078 10083

7. NakagawaI

KurokawaK

YamashitaA

NakataM

TomiyasuY

2003 Genome sequence of an M3 strain of Streptococcus pyogenes reveals a large-scale genomic rearrangement in invasive strains and new insights into phage evolution. Genome Res 13 1042 1055

8. Working Group on Severe Streptococcal Infections 1993 Defining the group A streptococcal toxic shock syndrome. JAMA 269 390 391

9. AlbertTJ

DailidieneD

DailideG

NortonJE

KaliaA

2005 Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori. Nat Methods 2 951 953

10. LyonWR

GibsonCM

CaparonMG

1998 A role for trigger factor and an rgg-like regulator in the transcription, secretion and processing of the cysteine proteinase of Streptococcus pyogenes. EMBO J 17 6263 6275

11. ChausseeMS

AjdicD

FerrettiJJ

1999 The rgg gene of Streptococcus pyogenes NZ131 positively influences extracellular SPE B production. Infect Immun 67 1715 1722

12. ChausseeMS

WatsonRO

SmootJC

MusserJM

2001 Identification of Rgg-regulated exoproteins of Streptococcus pyogenes. Infect Immun 69 822 831

13. ChausseeMS

SylvaGL

SturdevantDE

SmootLM

GrahamMR

2002 Rgg influences the expression of multiple regulatory loci to coregulate virulence factor expression in Streptococcus pyogenes. Infect Immun 70 762 770

14. HollandsA

AzizRK

KansalR

KotbM

NizetV

2008 A naturally occurring mutation in ropB suppresses SpeB expression and reduces M1T1 group A streptococcal systemic virulence. PLoS ONE 3 e4102 doi:10.1371/journal.pone.0004102

15. MaddenJC

RuizN

CaparonM

2001 Cytolysin-Mediated Translocation (CMT): A Functional Equivalent of Type III Secretion in Gram-Positive Bacteria. Cell 104 143 152

16. DmitrievAV

McDowellEJ

KappelerKV

ChausseeMA

RieckLD

2006 The Rgg regulator of Streptococcus pyogenes influences utilization of nonglucose carbohydrates, prophage induction, and expression of the NAD-glycohydrolase virulence operon. J Bacteriol 188 7230 7241

17. DmitrievAV

McDowellEJ

ChausseeMS

2008 Inter- and intraserotypic variation in the Streptococcus pyogenes Rgg regulon. FEMS Microbiol Lett 284 43 51

18. GrahamMR

SmootLM

MigliaccioCA

VirtanevaK

SturdevantDE

2002 Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling. Proc Natl Acad Sci 99 13855 13860

19. TreviñoJ

PerezN

Ramirez-PeñaE

LiuZ

ShelburneSA3rd

2009 CovS simultaneously activates and inhibits the CovR-mediated repression of distinct subsets of group A Streptococcus virulence factor-encoding genes. Infect Immun 77 3141 3149

20. BrickerAL

CareyVJ

WesselsMR

2005 Role of NADase in virulence in experimental invasive group A streptococcal infection. Infect Immun 73 6562 6566

21. SunH

RingdahlU

HomeisterJW

FayWP

EnglebergNC

2004 Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science 305 1283 1286

22. KreikemeyerB

McIverKS

PodbielskiA

2003 Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen-host interactions. Trends Microbiol 11 224 232

23. KotbM

Norrby-TeglundA

McGeerA

El-SherbiniH

DorakMT

2002 An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat Med 8 1398 1404

24. FactorSH

LevineOS

SchwartzB

HarrisonLH

FarleyMM

2003 Invasive group A streptococcal disease: risk factors for adults. Emerg Infect Dis 9 970 977

25. GladyshevaIP

TurnerRB

SazonovaIY

LiuL

ReedGL

2003 Coevolutionary patterns in plasminogen activation. Proc Natl Acad Sci USA 100 9168 9172

26. MillerLG

Perdreau-RemingtonF

RiegG

MehdiS

PerlrothJ

2005 Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med 352 1445 1453

27. ChambersHF

2005 Community-associated MRSA-resistance and virulence converge. N Engl J Med 352 1485 1487

28. VoyichJM

BraughtonKR

SturdevantDE

WhitneyAR

Saïd-SalimB

2005 Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J Immunol 175 3907 3919

29. WangR

BraughtonKR

KretschmerD

BachTH

QueckSY

2007 Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13 1510 1514

30. IkebeT

HirasawaK

SuzukiR

OhyaH

IsobeJ

2007 Distribution of emm genotypes among group A streptococus isolates from patients with severe invasive streptococcal infections in Japan, 2001-2005. Epidemiol Infect 135 1227 1229

31. TaoL

LeBlancDJ

FerrettiJJ

1992 Novel streptococcal integration shuttle vectors for gene cloning and inactivation. Gene 120 105 110

32. Perez-CasalJ

PriceJA

MaguinE

ScottJR

1993 An M protein with a single C repeat prevents phagocytosis of Streptococcus pyogenes: use of a temperature-sensitive shuttle vector to deliver homologous sequences to the chromosome of S. pyogenes. Mol Microbiol 8 809 819

33. IkebeT

HirasawaK

SuzukiR

IsobeJ

TanakaD

2005 Antimicrobial susceptibility survey of Streptococcus pyogenes isolated from severe invasive group A streptococcal infections in Japan. Antimicrob Agents Chemother 49 788 790

34. IkebeT

EndoM

UedaY

OkadaK

SuzukiR

2004 The genetic properties of Streptococcus pyogenes emm49 genotype strains recently emerged among severe invasive infections in Japan. Jpn J Infect Dis 57 187 188

35. InagakiY

KondaT

MurayamaS

YamaiS

MatsushimaA

1997 Serotyping of Streptococcus pyogenes isolates from common and severe invasive infections in Japan from 1990 to 1995. Epidemiol Infect 119 41 48

36. MoritaM

IkebeT

WatanabeH

2004 Consideration of the cysteine protease activity for the serological M typing of clinical Streptococcus pyogenes isolates. Miclobiol Immunol 48 779 782

37. IkebeT

WadaA

InagakiY

SugamaK

SuzukiR

2002 Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan. Infect Immun 70 3227 3233

38. IkebeT

EndohM

WatanabeH

2005 Increased expression of the ska gene in emm49-genotyped Streptococcus pyogenes strains isolated from patients with severe invasive streptococcal infections. Jpn J Infect Dis 58 272 275

39. LevinJC

WesselsMR

1998 Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A streptococcus. Mol Microbiol 30 209 219

40. InagakiY

MyougaF

KawabataH

YamaiS

WatanabeH

2000 Genomic differences in Streptococcus pyogenes serotype M3 between recent isolates associated with toxic shock-like syndrome and past clinical isolates. J Infect Dis 181 975 983

41. IkebeT

WadaA

InagakiY

SugamaK

SuzukiR

2002 Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan. Infect Immun 70 3227 3233