scholarly journals Streptococcus pyogenes prtFII, but not sfbI, sfbII or fbp54, is represented more frequently among invasive-disease isolates of tropical Australia

2002 ◽  
Vol 128 (3) ◽  
pp. 391-396 ◽  
Author(s):  
A. DELVECCHIO ◽  
B. J. CURRIE ◽  
J. D. McARTHUR ◽  
M. J. WALKER ◽  
K. S. SRIPRAKASH
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Host Cells ◽  
Non Invasive ◽  
Invasive Diseases ◽  
Genetic Endowment ◽  
Group A ◽  
Tropical Australia

Streptococcus pyogenes (group A streptococcus) strains may express several distinct fibronectin-binding proteins (FBPs) which are considered as major streptococcal adhesins. Of the FBPs, SfbI was shown in vitro to promote internalization of the bacterium into host cells and has been implicated in persistence. In the tropical Northern Territory, where group A streptococcal infection is common, multiple genotypes of the organism were found among isolates from invasive disease cases and no dominant strains were observed. To determine whether any FBPs is associated with invasive disease propensity of S. pyogenes, we have screened streptococcal isolates from bacteraemic and necrotizing fasciitis patients and isolates from uncomplicated infections for genetic endowment of 4 FBPs. No difference was observed in the distribution of sfbII, fbp54 and sfbI between the blood isolates and isolates from uncomplicated infection. We conclude that the presence of sfbI does not appear to promote invasive diseases, despite its association with persistence. We also show a higher proportion of group A streptococcus strains isolated from invasive disease cases possess prtFII when compared to strains isolated from non-invasive disease cases. We suggest that S. pyogenes may recruit different FBPs for different purposes.

scholarly journals SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion

2014 ◽  
Vol 82 (7) ◽  
pp. 2890-2901 ◽  
Author(s):  
Marilena Gallotta ◽  
Giovanni Gancitano ◽  
Giampiero Pietrocola ◽  
Marirosa Mora ◽  
Alfredo Pezzicoli ◽  
...  
Keyword(s):  
Cell Division ◽  
Mammalian Cells ◽  
Group A Streptococcus ◽  
Host Cells ◽  
Knockout Mutant ◽  
Content Type ◽  
Moonlighting Protein ◽  
Group A

ABSTRACTGroup A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of thespy0269gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interactin vitrowith the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cellsin vitroand thatLactococcus lactisexpressing Spy0269 on its cell surface could adhere to mammalian cellsin vitroand to mice nasal mucosain vivo. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (StreptococcuspyogenesAdhesion andDivision protein).

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

scholarly journals Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo

2005 ◽  
Vol 73 (9) ◽  
pp. 6026-6038 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Dennis G. Cvitkovitch ◽  
Peter Chang ◽  
Darrin J. Bast ◽  
Martin Handfield ◽  
...  
Keyword(s):  
Murine Model ◽  
Vibrio Vulnificus ◽  
Group A Streptococcus ◽  
Hypothetical Protein ◽  
Invasive Disease ◽  
Antigenic Determinants ◽  
Expression Library ◽  
Group A

ABSTRACT Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism. Convalescent-phase sera from patients with invasive disease were pooled, adsorbed against antigens derived from in vitro-grown GAS, and used to screen a GAS genomic expression library. A murine model of invasive GAS disease was included as an additional source of sera for screening. Sequencing DNA inserts from clones reactive with both human and mouse sera indicated 16 open reading frames with homology to genes involved in metabolic activity to genes of unknown function. Of these, seven genes were assessed for their differential expression by quantitative real-time PCR both in vivo, utilizing a murine model of invasive GAS disease, and in vitro at different time points of growth. Three gene products—a putative penicillin-binding protein 1A, a putative lipoprotein, and a conserved hypothetical protein homologous to a putative translation initiation inhibitor in Vibrio vulnificus—were upregulated in vivo, suggesting that these genes play a role during invasive disease.

scholarly journals Impact of M49, Mrp, Enn, and C5a Peptidase Proteins on Colonization of the Mouse Oral Mucosa by Streptococcus pyogenes

1998 ◽  
Vol 66 (11) ◽  
pp. 5399-5405 ◽  
Author(s):  
Yinduo Ji ◽  
Norbert Schnitzler ◽  
Eric DeMaster ◽  
Patrick Cleary
Keyword(s):  
Oral Mucosa ◽  
Streptococcus Pyogenes ◽  
Polymorphonuclear Leukocytes ◽  
Group A Streptococcus ◽  
M Protein ◽  
Insertion Mutation ◽  
Short Term ◽  
Group A ◽  
Isogenic Strains

ABSTRACT Resistance to phagocytosis is a hallmark of virulentStreptococcus pyogenes (group A streptococcus). Surface-bound C5a peptidase reduces recruitment of phagocytes to the site of infection, and hyaluronic acid capsules and/or the M protein limit the uptake of streptococci. In this study the relative impact of M and M-like proteins and the C5a peptidase on the virulence of a serotype M49 strain was assessed. The capacities of isogenic strains with an insertion mutation in emm49; with a deletion mutation in scpA49 (C5a peptidase gene); and with a deletion that removes all three M-like genes, mrp49,emm49, and enn49, to colonize mice and resist phagocytosis were compared. Experiments confirmed results obtained in an earlier study, which showed that the M49 protein was not required for in vitro resistance to phagocytosis, and also showed that the M protein was not required for colonization of mice. Failure to produce all three M-like proteins, M49, Mrp, and Enn49, significantly reduced the ability of these streptococci to resist phagocytosis in vitro but did not significantly alter the persistence of streptococci on the oral mucosa. In vitro experiments indicate that M+ streptococci are phagocytized by polymorphonuclear leukocytes that have been activated with phorbol-12-myristate 13-acetate or recombinant human C5a. This observation may explain the finding that expression of M49 protein is not essential for short-term colonization of the mouse oral mucosa.

scholarly journals Acquisition of the Sda1-Encoding Bacteriophage Does Not Enhance Virulence of the Serotype M1 Streptococcus pyogenes Strain SF370

2013 ◽  
Vol 81 (6) ◽  
pp. 2062-2069 ◽  
Author(s):  
Carola Venturini ◽  
Cheryl-lynn Y. Ong ◽  
Christine M. Gillen ◽  
Nouri L. Ben-Zakour ◽  
Peter G. Maamary ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Invasive Disease ◽  
Mutant Form ◽  
Transfer Event ◽  
Content Type ◽  
Lethal Infection ◽  
Group A ◽  
The Impact ◽  
Acting In Concert

ABSTRACTThe resurgence of invasive disease caused byStreptococcus pyogenes(group AStreptococcus[GAS]) in the past 30 years has paralleled the emergence and global dissemination of the highly virulent M1T1 clone. The GAS M1T1 clone has diverged from the ancestral M1 serotype by horizontal acquisition of two unique bacteriophages, encoding the potent DNase Sda1/SdaD2 and the superantigen SpeA, respectively. The phage-encoded DNase promotes escape from neutrophil extracellular traps and is linked to enhanced virulence of the M1T1 clone. In this study, we successfully usedin vitrolysogenic conversion to transfer the Sda1-encoding phage from the M1T1 clonal strain 5448 to the nonclonal M1 isolate SF370 and determined the impact of this horizontal gene transfer event on virulence. Although Sda1 was expressed in SF370 lysogens, no capacity of the phage-converted strain to survive human neutrophil killing, switch to a hyperinvasivecovRSmutant form, or cause invasive lethal infection in a humanized plasminogen mouse model was observed. This work suggests that the hypervirulence of the M1T1 clone is due to the unique synergic effect of the M1T1 clone bacteriophage-specific virulence factor Sda1 acting in concert with the M1T1 clone-specific genetic scaffold.

scholarly journals Distinct Time-Resolved Roles for Two Catabolite-Sensing Pathways duringStreptococcus pyogenesInfection

2010 ◽  
Vol 79 (2) ◽  
pp. 812-821 ◽  
Author(s):  
Colin C. Kietzman ◽  
Michael G. Caparon
Keyword(s):  
Streptococcus Pyogenes ◽  
Virulence Genes ◽  
Group A Streptococcus ◽  
Transcriptome Profiling ◽  
Time Resolved ◽  
Group A ◽  
Global Transcriptome ◽  
Carbon Catabolite Regulation ◽  
Catabolite Regulation

ABSTRACTMany Gram-positive pathogens link the expression of virulence genes to the presence of carbon source substrates using overlapping pathways for global control of carbon catabolite regulation. However, how these pathways are integrated to control the behavior of the transcriptome in time- and compartment-specific patterns is typically not well understood. In the present study, global transcriptome profiling was used to determine the extent to which glucose alters gene expression inStreptococcus pyogenes(group A streptococcus) and the contributions of the CcpA and LacD.1 catabolite control pathways to the regulation of this responsein vitro. This analysis revealed that the expression of as many as 15% of the genes examined was regulated and that CcpA and LacD.1 together contribute to the regulation of 60% of this subset. However, numerous patterns were observed, including both CcpA- and LacD.1-specific and independent regulation, coregulation, and regulation of genes by these pathways independently of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most coregulated genes. To resolve the roles of these regulators during infection, the expression of selected transcripts representative of different regulatory patterns was examined in a murine model of soft tissue infection. This revealed distinct patterns of misregulation with respect to time in CcpA−versus LacD.1−mutants. Taken together, these data support an important role for carbohydrate in the regulation of the transcriptome in tissue and suggest that the CcpA and LacD.1 pathways are organized to function at different times during the course of an infection.

scholarly journals A role for glutathione in buffering excess intracellular copper in Streptococcus pyogenes

2020 ◽  
Author(s):  
Louisa J. Stewart ◽  
Cheryl-lynn Y. Ong ◽  
May M. Zhang ◽  
Stephan Brouwer ◽  
Liam McIntyre ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Metal Binding ◽  
Metal Ion ◽  
Invasive Disease ◽  
Metal Availability ◽  
Bacterial Physiology ◽  
Fundamental Understanding ◽  
Group A

ABSTRACTCopper (Cu) is an essential metal for bacterial physiology but in excess it is bacteriotoxic. To limit Cu levels in the cytoplasm, most bacteria possess a transcriptionally-responsive system for Cu export. In the Gram-positive human pathogen Streptococcus pyogenes (Group A Streptococcus, GAS), this system is encoded by the copYAZ operon. In this study, we demonstrate that the site of GAS infection in vivo represents a Cu-rich environment but inactivation of the copA Cu efflux gene does not reduce virulence in a mouse model of invasive disease. In vitro, Cu treatment leads to multiple observable phenotypes, including defects in growth and viability, decreased fermentation, inhibition of glyceraldehyde 3-phosphate dehydrogenase (GapA) activity, and misregulation of metal homeostasis, likely as a consequence of mismetalation of non-cognate metal-binding sites. Surprisingly, the onset of these effects is delayed by ∼4 h even though expression of copZ is upregulated immediately upon exposure to Cu. We further show that the onset of all phenotypes coincides with depletion of intracellular glutathione (GSH). Supplementation with extracellular GSH replenishes the intracellular pool of this thiol and suppresses all the observable effects of Cu treatment. Our results indicate that GSH contributes to buffering of excess intracellular Cu when the transcriptionally-responsive Cu export system is overwhelmed. Thus, while the copYAZ operon is responsible for Cu homeostasis, GSH has a role in Cu tolerance that allows bacteria to maintain metabolism even in the presence of an excess of this metal ion. This study advances fundamental understanding of Cu handling in the bacterial cytoplasm.IMPORTANCEThe control of intracellular metal availability is fundamental to bacterial physiology. In the case of copper (Cu), it is established that rising intracellular Cu levels eventually fill the metal-sensing site of the endogenous Cu-sensing transcriptional regulator, which in turn induces transcription of a copper export pump. This response caps intracellular Cu availability below a well-defined threshold and prevents Cu toxicity. Glutathione, abundant in many bacteria, is known to bind Cu and is long assumed to contribute to bacterial Cu handling. However, there is some ambiguity since neither its biosynthesis nor uptake is Cu-regulated. Furthermore, there is little experimental support for this role of glutathione beyond measurement of the effect of Cu on growth of glutathione-deficient mutants. Our work with Group A Streptococcus provides new evidence that glutathione increases the threshold of intracellular Cu availability that can be tolerated by bacteria and thus advances fundamental understanding of bacterial Cu handling.

scholarly journals Ongoing outbreak of invasive and non-invasive disease due to group A Streptococcus (GAS) type emm66 among homeless and people who inject drugs in England and Wales, January to December 2016

2017 ◽  
Vol 22 (3) ◽  
Author(s):  
Nick Bundle ◽  
Laura Bubba ◽  
Juliana Coelho ◽  
Rachel Kwiatkowska ◽  
Rachel Cloke ◽  
...  
Keyword(s):  
People Who Inject Drugs ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Homeless Population ◽  
England And Wales ◽  
Non Invasive ◽  
Group A ◽  
Common Risk Factors ◽  
Problematic Alcohol Use ◽  
Unusual Type

We report an outbreak of invasive and non-invasive disease due to an unusual type of Streptococcus pyogenes (group A Streptococcus, emm66) among a vulnerable, largely homeless population in southern England and Wales, detected in September 2016. Twenty-seven confirmed cases were subsequently identified between 5 January and 29 December 2016; 20 injected drugs and six reported problematic alcohol use. To date, we have ruled out drug-related vehicles of infection and identified few common risk factors.

scholarly journals Complete Genome Sequences of Streptococcus pyogenes Serotype M3, M28, and M89 Strains Isolated from Human Patients in Japan, 1994 to 2009

2020 ◽  
Vol 9 (42) ◽  
Author(s):  
Kazunori Murase ◽  
Takashi Nozawa ◽  
Chihiro Aikawa ◽  
Miki Nagao ◽  
Tadayoshi Ikebe ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Complete Genome ◽  
Invasive Disease ◽  
Human Pathogen ◽  
Genome Sequences ◽  
Content Type ◽  
Invasive Diseases ◽  
Life Threatening ◽  
Group A

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is a major human pathogen that occasionally causes severe and life-threatening invasive diseases. Here, we report the complete genome sequences of four GAS strains of three M types, which were isolated from patients with severe invasive disease in Japan.

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.

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