Mutational analysis of the group A streptococcal operon encoding streptolysin S and its virulence role in invasive infection

  title={Mutational analysis of the group A streptococcal operon encoding streptolysin S and its virulence role in invasive infection},
  author={Vivekananda Datta and Sandra M Myskowski and Laura A Kwinn and Daniel N Chiem and Nissi Varki and Rita Kansal and Malak Kotb and Victor Nizet},
  journal={Molecular Microbiology},
The pathogen group A Streptococcus (GAS) produces a wide spectrum of infections including necrotizing fasciitis (NF). Streptolysin S (SLS) produces the hallmark β‐haemolytic phenotype produced by GAS. The nine‐gene GAS locus (sagA–sagI) resembling a bacteriocin biosynthetic operon is necessary and sufficient  for  SLS  production.  Using  precise,  in‐frame allelic exchange mutagenesis and single‐gene complementation, we show sagA, sagB, sagC, sagD, sagE, sagF and sagG are each individually… 
Genetic Characterization and Virulence Role of the RALP3/LSA Locus Upstream of the Streptolysin S Operon in Invasive M1T1 Group A Streptococcus
First mutational analysis of a genetic locus immediately upstream of the streptolysin S biosynthetic operon in several GAS genome sequences, identifying RALP3 as a global transcriptional regulator affecting expression of numerous virulence factor genes, including those for strong repression of the hyaluronic acid capsule and cysteine protease production.
Streptococcus iniae beta-hemolysin streptolysin S is a virulence factor in fish infection.
The isogenic Delta sagA mutant was less cytotoxic to fish blood cells and cultured epithelial cells, but comparable to wild-type (WT) S. iniae in adherence/invasion of epithelial cell monolayers and resisting phagocytic killing by fish whole blood or macrophages.
Identification of β-haemolysin-encoding genes in Streptococcus anginosus.
Using a genomic mutagenesis strategy, a gene cluster with high homology to the genes of the streptolysin S (SLS) encoding sag gene cluster of S.anginosus is determined and its importance for β-haemolysin production in S. anginous is demonstrated.
Characterisation of group A streptococcal innate immune resistance and host response mechanisms
High-throughput next-generation sequencing was utilised to generate a draft genome sequence of NS88.2, an emm98.1 GAS isolate exhibiting a hypervirulent and PMN resistant phenotype, and the multi-locus sequence type (MLST) was determined.
M Protein and Hyaluronic Acid Capsule Are Essential for In Vivo Selection of covRS Mutations Characteristic of Invasive Serotype M1T1 Group A Streptococcus
It is found that M1 protein and hyaluronic acid capsule are indispensable for the switching phenotype, a phenomenon previously attributed uniquely to the Sda1 DNase, and a novel role for capsule in GAS resistance to host defense peptides and neutrophil extracellular killing is revealed.
The two-component system sivS/R regulates virulence in Streptococcus iniae.
It is shown that a sivS/R deletion-insertion mutant, termed 9117Deltasiv, causes transient bacteremia and reduced virulence compared with the parent strain when tested in a murine model of b acteremic infection.
CcpA-Mediated Repression of Streptolysin S Expression and Virulence in the Group A Streptococcus
CcpA acts to repress SLS activity and virulence during systemic infection in mice, revealing an important link between carbon metabolism and GAS pathogenesis.
The Abi-domain Protein Abx1 Interacts with the CovS Histidine Kinase to Control Virulence Gene Expression in Group B Streptococcus
A regulatory function is reported for Abx1, a member of a large protein family with a characteristic Abi-domain, which forms a signaling complex with the histidine kinase CovS in GBS, a leading cause of invasive infections in neonates.
Study of streptococcal hemoprotein receptor (Shr) in iron acquisition and virulence of M1T1 group A streptococcus
It is concluded that Shr augments GAS adherence to laminin, an important extracellular matrix attachment component, which contributes to GAS growth in human blood, and is required for full virulence of serotype M1T1 GAS in mouse models of invasive disease.
A Conserved UDP-Glucose Dehydrogenase Encoded outside the hasABC Operon Contributes to Capsule Biogenesis in Group A Streptococcus
It is concluded that HasB is not essential for M1T1 GAS capsule biogenesis due to the presence of a newly identified HasB paralog, HasB2, which most likely resulted from gene duplication.


Genetic Locus for Streptolysin S Production by Group A Streptococcus
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
Combined Contributions of Streptolysin O and Streptolysin S to Virulence of Serotype M5 Streptococcus pyogenes Strain Manfredo
Interestingly, in some cases, the contribution of SLO to virulence was clear only from an analysis of the double-mutant strain, highlighting the value of not confining virulence studies to mutant strains defective in the expression of only single virulence factors.
Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis of Streptococcus iniae Disease
It is 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.
Mouse skin passage of a Streptococcus pyogenes Tn917 mutant of sagA/pel restores virulence, beta-hemolysis and sagA/pel expression without altering the position or sequence of the transposon
These results show that biological pressure present in the mouse can select for variants with altered expression of key virulence factor genes in S. pyogenes.
Identification of pel, aStreptococcus pyogenes Locus That Affects both Surface and Secreted Proteins
Characterization of the pel mutant provides evidence for the coordinated regulation of secreted and surface proteins and suggests the existence of a new global regulatory factor in S. pyogenes.
Contribution of CsrR-Regulated Virulence Factors to the Progress and Outcome of Murine Skin Infections by Streptococcus pyogenes
It is concluded that capsule and SLS contribute to the subcutaneous spread of S. pyogenes and to a fatal outcome of infection.
Molecular basis of group A streptococcal virulence.
A Response Regulator That Represses Transcription of Several Virulence Operons in the Group A Streptococcus
CovR is the first multiple-gene repressor of virulence factors described for this important human pathogen, demonstrating that the CovR-CovS pathway is separate from growth phase-dependent regulation in GAS.
Streptococcal β-hemolysins: genetics and role in disease pathogenesis