Activation of band 3 mediates group A Streptococcus streptolysin S-based beta-haemolysis

2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Dustin L. Higashi ◽  
Nicolas Biais ◽  
Deborah L. Donahue ◽  
Jeffrey A. Mayfield ◽  
Charles R. Tessier ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Band 3 ◽  
Streptolysin S ◽  
Group A

scholarly journals Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis of Streptococcus iniae Disease

2002 ◽  
Vol 70 (10) ◽  
pp. 5730-5739 ◽  
Author(s):  
Jeffrey D. Fuller ◽  
Alvin C. Camus ◽  
Carla L. Duncan ◽  
Victor Nizet ◽  
Darrin J. Bast ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Genomic Region ◽  
Infection Model ◽  
Streptococcus Iniae ◽  
Genetic Profile ◽  
Tissue Necrosis ◽  
Chromosomal Locus ◽  
Local Tissue ◽  
Streptolysin S ◽  
Group A

ABSTRACT Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model. The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J. D. Fuller, D. J. Bast, V. Nizet, D. E. Low, and J. C. S. de Azavedo, Infect. Immun. 69:1994-2000, 2001). S. iniae produces a cytolysin that confers a hemolytic phenotype on blood agar media. In this study, we characterized the genomic region responsible for S. iniae cytolysin production and assessed its contribution to virulence. Transposon (Tn917) mutant libraries of commensal and disease-associated S. iniae strains were generated and screened for loss of hemolytic activity. Analysis of two nonhemolytic mutants identified a chromosomal locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag operon for streptolysin S (SLS) biosynthesis. Confirmation that the S. iniae cytolysin is a functional homologue of SLS was achieved by PCR ligation mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS inhibitor trypan blue. SLS-negative sagB mutants were compared to their wild-type S. iniae parent strains in the murine model and in human whole-blood killing assays. These studies demonstrated that S. iniae SLS expression is required for local tissue necrosis but does not contribute to the establishment of bacteremia or to resistance to phagocytic clearance.

scholarly journals A Response Regulator That Represses Transcription of Several Virulence Operons in the Group A Streptococcus

1999 ◽  
Vol 181 (12) ◽  
pp. 3649-3657 ◽  
Author(s):  
Michael J. Federle ◽  
Kevin S. McIver ◽  
June R. Scott
Keyword(s):  
Group A Streptococcus ◽  
Response Regulator ◽  
Regulatory System ◽  
Insertion Mutant ◽  
Multiple Gene ◽  
Streptolysin S ◽  
Streptolysin O ◽  
Group A ◽  
Complement C5a ◽  
Global Regulatory System

ABSTRACT A search for homologs of the Bacillus subtilis PhoP response regulator in the group A streptococcus (GAS) genome revealed three good candidates. Inactivation of one of these, recently identified as csrR (J. C. Levin and M. R. Wessels, Mol. Microbiol. 30:209–219, 1998), caused the strain to produce mucoid colonies and to increase transcription ofhasA, the first gene in the operon for capsule synthesis. We report here that a nonpolar insertion in this gene also increased transcription of ska (encoding streptokinase),sagA (streptolysin S), and speMF (mitogenic factor) but did not affect transcription of slo(streptolysin O), mga (multiple gene regulator of GAS),emm (M protein), scpA (complement C5a peptidase), or speB or speC (pyrogenic exotoxins B and C). The amounts of streptokinase, streptolysin S, and capsule paralleled the levels of transcription of their genes in all cases. Because CsrR represses genes unrelated to those for capsule synthesis, and because CsrA-CsrB is a global regulatory system inEscherichia coli whose mechanism is unrelated to that of these genes in GAS, the locus has been renamed covR, for “control of virulence genes” in GAS. Transcription of thecovR operon was also increased in the nonpolar insertion mutant, indicating that CovR represses its own synthesis as well. All phenotypes of the covR nonpolar insertion mutant were complemented by the covR gene on a plasmid. CovR acts on operons expressed both in exponential and in stationary phase, demonstrating that the CovR-CovS pathway is separate from growth phase-dependent regulation in GAS. Therefore, CovR is the first multiple-gene repressor of virulence factors described for this important human pathogen.

scholarly journals CcpA-Mediated Repression of Streptolysin S Expression and Virulence in the Group A Streptococcus

2008 ◽  
Vol 76 (8) ◽  
pp. 3451-3463 ◽  
Author(s):  
Traci L. Kinkel ◽  
Kevin S. McIver
Keyword(s):  
Group A Streptococcus ◽  
Intraperitoneal Administration ◽  
Subcutaneous Administration ◽  
Sugar Metabolism ◽  
Virulence Gene ◽  
Systemic Infection ◽  
Lesion Size ◽  
Logarithmic Phase ◽  
Streptolysin S ◽  
Group A

ABSTRACT CcpA is the global mediator of carbon catabolite repression (CCR) in gram-positive bacteria, and growing evidence from several pathogens, including the group A streptococcus (GAS), suggests that CcpA plays an important role in virulence gene regulation. In this study, a deletion of ccpA in an invasive M1 GAS strain was used to test the contribution of CcpA to pathogenesis in mice. Surprisingly, the ΔccpA mutant exhibited a dramatic “hypervirulent” phenotype compared to the parental MGAS5005 strain, reflected as increased lethality in a model of systemic infection (intraperitoneal administration) and larger lesion size in a model of skin infection (subcutaneous administration). Expression of ccpA in trans from its native promoter was able to complement both phenotypes, suggesting that CcpA acts to repress virulence in GAS. To identify the CcpA-regulated gene(s) involved, a transcriptome analysis was performed on mid-logarithmic-phase cells grown in rich medium. CcpA was found to primarily repress 6% of the GAS genome (124 genes), including genes involved in sugar metabolism, transcriptional regulation, and virulence. Notably, the entire sag operon necessary for streptolysin S (SLS) production was under CcpA-mediated CCR, as was SLS hemolytic activity. Purified CcpA-His bound specifically to a cre within sagAp, demonstrating direct repression of the operon. Finally, SLS activity is required for the increased virulence of a ΔccpA mutant during systemic infection but did not affect virulence in a wild-type background. Thus, CcpA acts to repress SLS activity and virulence during systemic infection in mice, revealing an important link between carbon metabolism and GAS pathogenesis.

scholarly journals Requirement and Synergistic Contribution of Platelet-Activating Factor Acetylhydrolase Sse and Streptolysin S to Inhibition of Neutrophil Recruitment and Systemic Infection by Hypervirulent emm3 Group A Streptococcus in Subcutaneous Infection of Mice

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Wenchao Feng ◽  
Dylan Minor ◽  
Mengyao Liu ◽  
Benfang Lei
Keyword(s):  
Skin Infection ◽  
Group A Streptococcus ◽  
Platelet Activating Factor ◽  
Systemic Infection ◽  
Lesion Size ◽  
Neutrophil Recruitment ◽  
Subcutaneous Infection ◽  
Streptolysin S ◽  
Platelet Activating Factor Acetylhydrolase ◽  
Group A

ABSTRACT Hypervirulent group A streptococcus (GAS) can inhibit neutrophil recruitment and cause systemic infection in a mouse model of skin infection. The purpose of this study was to determine whether platelet-activating factor acetylhydrolase Sse and streptolysin S (SLS) have synergistic contributions to inhibition of neutrophil recruitment and systemic infection in subcutaneous infection of mice by MGAS315, a hypervirulent genotype emm3 GAS strain. Deletion of sse and sagA in MGAS315 synergistically reduced the skin lesion size and GAS burden in the liver and spleen. However, the mutants were persistent at skin sites and had similar growth factors in nonimmune blood. Thus, the low numbers of Δsse ΔsagA mutants in the liver and spleen were likely due to their reduction in the systemic dissemination. Few intact and necrotic neutrophils were detected at MGAS315 infection sites. In contrast, many neutrophils and necrotic cells were present at the edge of Δsse mutant infection sites on day 1 and at the edge of and inside Δsse mutant infection sites on day 2. ΔsagA mutant infection sites had massive numbers of and few intact neutrophils at the edge and center of the infection sites, respectively, on day 1 and were full of intact neutrophils or necrotic cells on day 2. Δsse ΔsagA mutant infection sites had massive numbers of intact neutrophils throughout the whole infection site. These sse and sagA deletion-caused changes in the histological pattern at skin infection sites could be complemented. Thus, the sse and sagA deletions synergistically enhance neutrophil recruitment. These findings indicate that both Sse and SLS are required but that neither is sufficient for inhibition of neutrophil recruitment and systemic infection by hypervirulent GAS.

scholarly journals Cellular streptolysin S-related hemolysins of group A Streptococcus C203S.

1975 ◽  
Vol 12 (1) ◽  
pp. 13-28 ◽  
Author(s):  
G B Calandra ◽  
E L Oginsky
Keyword(s):  
Group A Streptococcus ◽  
Streptolysin S ◽  
Group A

scholarly journals Hemolytic mutants of group A Streptococcus pyogenes

1978 ◽  
Vol 7 (2) ◽  
pp. 153-157
Author(s):  
W Owens ◽  
F Henley ◽  
B D Barridge
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Nicotinamide Adenine ◽  
Streptolysin S ◽  
Naturally Occurring ◽  
Streptolysin O ◽  
Group A ◽  
The Dead

Hemolytic mutants of Lancefield strain SS-95 and ATCC 19615 Streptococcus pyogenes were produced by treatment with N-methyl-N'-nitro-N-nitrosoguanidine. These mutants contained the same levels of streptolysin O, nicotinamide adenine dinucleotidase, deoxyribonuclease, and hyaluronidase. The mutants were deficient in streptolysin S, as was the naturally occurring nonhemolytic Lowry strain. The mutants retained their pathogenicity for mice and, when reisolated from the dead animals, produced the mutant hemolytic pattern.

scholarly journals Signaling Peptide SpoV Is Essential for Streptococcus pyogenes Virulence, and Prophylaxis with Anti-SpoV Decreases Disease Severity

2021 ◽  
Vol 9 (11) ◽  
pp. 2321
Author(s):  
Andrea L. Herrera ◽  
Michael S. Chaussee
Keyword(s):  
Streptococcus Pyogenes ◽  
Therapeutic Potential ◽  
Group A Streptococcus ◽  
Ex Vivo ◽  
Invasive Disease ◽  
Human Model ◽  
Streptolysin S ◽  
Streptolysin O ◽  
Group A ◽  
Specific Peptide

Streptococcal peptide of virulence (SpoV) is a Streptococcus pyogenes (group A streptococcus (GAS))-specific peptide that is important for GAS survival in murine blood, and the expression of the virulence factors streptolysin O (slo) and streptolysin S (sagA). We used a spoV mutant in isolate MGAS315 to assess the contribution of the SpoV peptide to virulence by using a murine model of invasive disease and an ex vivo human model (Lancefield assay). We then used antibodies to SpoV in both models to evaluate their ability to decrease morbidity and mortality. Results showed that SpoV is essential for GAS virulence, and targeting the peptide has therapeutic potential.

scholarly journals Genetic Locus for Streptolysin S Production by Group A Streptococcus

2000 ◽  
Vol 68 (7) ◽  
pp. 4245-4254 ◽  
Author(s):  
Victor Nizet ◽  
Bernard Beall ◽  
Darrin J. Bast ◽  
Vivekananda Datta ◽  
Laurie Kilburn ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Genetic Locus ◽  
Plasmid Vector ◽  
Gene Products ◽  
Knockout Mutant ◽  
Sequencing Project ◽  
Streptolysin S ◽  
Invasive Infections ◽  
Group A ◽  
Terminator Sequence

ABSTRACT Group A streptococcus (GAS) is an important human pathogen that causes pharyngitis and invasive infections, including necrotizing fasciitis. Streptolysin S (SLS) is the cytolytic factor that creates the zone of beta-hemolysis surrounding GAS colonies grown on blood agar. We recently reported the discovery of a potential genetic determinant involved in SLS production, sagA, encoding a small peptide of 53 amino acids (S. D. Betschel, S. M. Borgia, N. L. Barg, D. E. Low, and J. C. De Azavedo, Infect. Immun. 66:1671–1679, 1998). Using transposon mutagenesis, chromosomal walking steps, and data from the GAS genome sequencing project (www.genome.ou.edu/strep.html ), we have now identified a contiguous nine-gene locus (sagA to sagI) involved in SLS production. The sag locus is conserved among GAS strains regardless of M protein type. Targeted plasmid integrational mutagenesis of each gene in the sag operon resulted in an SLS-negative phenotype. Targeted integrations (i) upstream of the sagA promoter and (ii) downstream of a terminator sequence after sagI did not affect SLS production, establishing the functional boundaries of the operon. A rho-independent terminator sequence between sagA andsagB appears to regulate the amount of sagAtranscript produced versus transcript for the entire operon. Reintroduction of the nine-gene sag locus on a plasmid vector restored SLS activity to the nonhemolytic sagAknockout mutant. Finally, heterologous expression of the intactsag operon conferred the SLS beta-hemolytic phenotype to the nonhemolytic Lactococcus lactis. We conclude that gene products of the GAS sag operon are both necessary and sufficient for SLS production. Sequence homologies of sagoperon gene products suggest that SLS is related to the bacteriocin family of microbial toxins.

scholarly journals The Phosphoenolpyruvate Phosphotransferase System in Group A Streptococcus Acts To Reduce Streptolysin S Activity and Lesion Severity during Soft Tissue Infection

2013 ◽  
Vol 82 (3) ◽  
pp. 1192-1204 ◽  
Author(s):  
Kanika Gera ◽  
Tuquynh Le ◽  
Rebecca Jamin ◽  
Zehava Eichenbaum ◽  
Kevin S. McIver
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Infection ◽  
Group A Streptococcus ◽  
Carbon Sources ◽  
Tissue Infection ◽  
Growth Defect ◽  
Wild Type ◽  
Phosphotransferase System ◽  
Streptolysin S ◽  
Group A

ABSTRACTObtaining essential nutrients, such as carbohydrates, is an important process for bacterial pathogens to successfully colonize host tissues. The phosphoenolpyruvate phosphotransferase system (PTS) is the primary mechanism by which bacteria transport sugars and sense the carbon state of the cell. The group A streptococcus (GAS) is a fastidious microorganism that has adapted to a variety of niches in the human body to elicit a wide array of diseases. A ΔptsImutant (enzyme I [EI] deficient) generated in three different strains of M1T1 GAS was unable to grow on multiple carbon sources (PTS and non-PTS). Complementation withptsIexpressed under its native promoter in single copy was able to rescue the growth defect of the mutant. In a mouse model of GAS soft tissue infection, all ΔptsImutants exhibited a significantly larger and more severe ulcerative lesion than mice infected with the wild type. Increased transcript levels ofsagAand streptolysin S (SLS) activity during exponential-phase growth was observed. We hypothesized that early onset of SLS activity would correlate with the severity of the lesions induced by the ΔptsImutant. In fact, infection of mice with a ΔptsI sagBdouble mutant resulted in a lesion comparable to that of either the wild type or asagBmutant alone. Therefore, a functional PTS is not required for subcutaneous skin infection in mice; however, it does play a role in coordinating virulence factor expression and disease progression.

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