Mitogenic factor secreted by Streptococcus pyogenes is a heat-stable nuclease requiring His122 for activity

Iwasaki, Makoto; Igarashi, Hisanaga; Yutsudo, Takashi

doi:10.1099/00221287-143-7-2449

Cited by 40 publications

(38 citation statements)

References 35 publications

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“…We considered the possibility that two virtually identical genes might co-exist in the S. pyogenes genome, though this was excluded in the wild-type strain we studied as only a single 1 kb fragment hybridized to the mf probe following NdeI genomic digestion. Identity at the protein level was first suggested by Iwasaki et al (1997), who demonstrated that recombinant MF had DNase activity in addition to the mitogenic actions shown in earlier work. A subsequent study from Sweden showed that the two proteins were immunologically identical using polyclonal antisera (Eriksson et al, 1999).…”

Section: Discussionmentioning

confidence: 73%

“…Recombinant MF is reported to have nuclease activity and separate studies have shown that MF and the streptococcal nuclease DNase B share identical immunologic epitopes (Eriksson et al, 1999 ;Iwasaki et al, 1997), suggesting that the two proteins are equivalent. Antibodies to both DNase B and MF have been detected in patients recovering from streptococcal sepsis, showing that these proteins are synthesized by pathogenic streptococci during infection (Gerber et al, 1980 ;Norrby-Teglund et al, 1994a).…”

Section: Introductionmentioning

confidence: 99%

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Mitogenic factor (MF) is the major DNase of serotype M89 Streptococcus pyogenes

et al. 2000

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To investigate the role of mitogenic factor (MF) in streptococcal pathogenesis, the structural gene (mf) encoding this protein was disrupted in a clinical isolate of Streptococcus pyogenes H293, to yield the isogenic mutant H363. Growth in enriched broth and on blood agar was unaffected by disruption of mf. Cell-free broth supernatants from H293 and H363 demonstrated identical promitogenic activities when co-incubated with human peripheral blood mononuclear cells, even when diluted 100 000-fold, showing that MF is not a major streptococcal mitogen compared with other secreted superantigens. Disruption of mf resulted in complete loss of DNase B production and detectable DNase activity in H363 compared with the parent strain, confirming that the single gene mf, which is present in all group A streptococcal M serotypes studied, encodes DNase B. Despite loss of DNase activity, the virulence of S. pyogenes in a mouse model of necrotizing fasciitis and myositis was unaffected.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Mitogenic factor (MF) is the major DNase of serotype M89 Streptococcus pyogenes

et al. 2000

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“…The individual effects of the speC and speF genes in the pathogenesis of invasive GAS infection are unclear. SpeF is known as a multifunctional protein that has mitogenic, superantigenic, nuclease, and vascular permeabilization activities (16,28). SpeX (also called SMEZ3), a superantigen, preferentially stimulates V␤8…”

Section: Discussionmentioning

confidence: 99%

Effects of Oligopeptide Permease in Group A Streptococcal Infection

Wang

Lin²,

Luo

et al. 2005

Infect Immun

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The oligopeptide permease (Opp) of group A streptococci (GAS) is a membrane-associated protein and belongs to the ATP-binding cassette transporter family. It is encoded by a polycistronic operon containing oppA, oppB, oppC, oppD, and oppF. The biological function of these genes in GAS is poorly understood. In order to understand more about the effects of Opp on GAS virulence factors, an oppA isogenic mutant was constructed by using an integrative plasmid to disrupt the opp operon and confirmed by Southern blot hybridization. No transcript was detected in the oppA isogenic mutant by Northern blot analysis and reverse transcriptase PCR. The growth curve for the oppA isogenic mutant was similar to that for wild-type strain A-20. The oppA isogenic mutant not only decreased the transcription of speB, speX, and rofA but also increased the transcription of speF, sagA (streptolysin S-associated gene A), slo (streptolysin O), pel (pleotrophic effect locus), and dppA (dipeptide permease). No effects on the transcription of emm, sda, speJ, speG, rgg, and csrR were found. The phenotypes of the oppA mutant were restored by the oppA revertant and by the complementation strain. The oppA mutant caused less mortality and tissue damage than the wild-type strain when inoculated into BALB/c mice via an air pouch. Based on these data, we suggest that the opp operon plays an important role in the pathogenesis of GAS infection.Group A streptococci (GAS) are important human pathogens that cause pharyngitis, impetigo, and many other human respiratory tract and soft tissue infections. A number of regulators, such as Mga, RofA, Rgg, Dpp, Nra, CsrS/CsrR, Pel, Fas, RelA, and oligopeptide permease (Opp), are likely to have regulatory roles in the expression of the virulence genes of GAS (3,6,13,17,18,29,35,36,38,44). The expression of M protein, C5a peptidase, serum opacity factor, streptococcin A, and streptococcal pyrogenic exotoxin B (SpeB) is positively regulated by Mga, a transcriptional activator protein (37) which is predicted to be a response regulator of the streptococcal two-component system (38). In addition to being positively regulated by Mga, the expression of SpeB is also positively regulated by Rgg, Opp, and Dpp (6,35,36) and negatively regulated by the two-component system CsrS/CsrR (13).Opp has been identified in several gram-negative and grampositive bacteria (21). It belongs to the ATP-binding cassette (ABC) transporter superfamily (33). The opp operon encodes five proteins, including a periplasmic binding protein (OppA), two transmembrane proteins (OppB and OppC) believed to form a channel for passage of the substrate, and two membrane-associated cytoplasmic ATPases (OppD and OppF) (36). ABC transporters have been shown to be important in the Agrobacterium tumefaciens response to opines (9), the competence of Streptococcus pneumoniae (14), and the uptake of oligopeptides of three to six amino acids in Salmonella enterica serovar Typhimurium, Bacillus subtilis, Lactococcus lactis, and Streptococcus agalactiae (7,21,42). T...

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“…Four immunologically and electrophoretically distinct nucleases, designated DNases A, B, C, and D, have been previously identified in S. pyogenes supernatant fluids (45,46). DNase D is encoded by the sdaD gene (35), and MF is thought to be identical to the protein previously described as DNase B (16). It is unclear if DNA entry nuclease (ORF 226) is identical to enzymes previously designated DNase A or C. ORF 226 is approximately 30% identical to several nucleases, including streptodornase (accession number X84793), EndA of Streptococcus pneumoniae (23), and MF (accession number D13428).…”

Section: Figmentioning

confidence: 99%

Identification of Rgg-Regulated Exoproteins of Streptococcus pyogenes

et al. 2001

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Streptococcus pyogenes secretes many proteins that influence host-pathogen interactions. Despite their importance, relatively little is known about the regulation of these proteins. The rgg gene (also known as ropB) is required for the expression of streptococcal erythrogenic toxin B (SPE B), an extracellular cysteine protease that contributes to virulence. Proteomics was used to determine if rgg regulates the expression of additional exoproteins. Exponential-and stationary-phase culture supernatant proteins made by S. pyogenes NZ131 rgg and NZ131 speB were separated by two-dimensional electrophoresis. Differences were identified in supernatant proteins from both exponential-and stationary-phase cultures, although considerably more differences were detected among stationary-phase supernatant proteins. Forty-two proteins were identified by peptide fingerprinting with matrix-assisted laser desorption mass spectrometry. Mitogenic factor, DNA entry nuclease (open reading frame [ORF 226]), and ORF 953, which has no known function, were more abundant in the culture supernatants of the rgg mutant compared to the speB mutant. ClpB, lysozyme, and autolysin were detected in the culture supernatant of the speB mutant but not the rgg mutant. To determine if Rgg affected protein expression at the transcriptional level, real-time (TaqMan) reverse transcription (RT)-PCR was used to quantitate Rgg-regulated transcripts from NZ131 wild-type and speB and rgg mutant strains. The results obtained with RT-PCR correlated with the proteomic data. We conclude that Rgg regulates the transcription of several genes expressed primarily during the stationary phase of growth.

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Mitogenic factor secreted by Streptococcus pyogenes is a heat-stable nuclease requiring His122 for activity

Cited by 40 publications

References 35 publications

Mitogenic factor (MF) is the major DNase of serotype M89 Streptococcus pyogenes

Mitogenic factor (MF) is the major DNase of serotype M89 Streptococcus pyogenes

Effects of Oligopeptide Permease in Group A Streptococcal Infection

Identification of Rgg-Regulated Exoproteins of Streptococcus pyogenes

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