skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: SpyB, a small heme-binding protein, affects the composition of the cell wall in Streptococcus pyogenes

Journal Article · · Frontiers in Cellular and Infection Microbiology
 [1];  [1];  [2];  [3];  [1];  [4];  [4];  [4];  [3];  [3];  [1];  [1];  [2];  [1]
  1. Univ. of Kentucky, Lexington, KY (United States)
  2. The Ohio State Univ., Columbus, OH (United States)
  3. Univ. of Washington, Seattle, WA (United States)
  4. Univ. of Georgia, Athens, GA (United States)

Streptococcus pyogenes (Group A Streptococcus or GAS) is a hemolytic human pathogen associated with a wide variety of infections ranging from minor skin and throat infections to life-threatening invasive diseases. The cell wall of GAS consists of peptidoglycan sacculus decorated with a carbohydrate comprising a polyrhamnose backbone with immunodominant N-acetylglucosamine side-chains. All GAS genomes contain the spyBA operon, which encodes a 35-amino-acid membrane protein SpyB, and a membrane-bound C3-like ADP-ribosyltransferase SpyA. In this study, we addressed the function of SpyB in GAS. Phenotypic analysis of a spyB deletion mutant revealed increased bacterial aggregation, and reduced sensitivity to β-lactams of the cephalosporin class and peptidoglycan hydrolase PlyC. Glycosyl composition analysis of cell wall isolated from the spyB mutant suggested an altered carbohydrate structure compared with the wild-type strain. Furthermore, we found that SpyB associates with heme and protoporphyrin IX. Heme binding induces SpyB dimerization, which involves disulfide bond formation between the subunits. Furthermore, our data suggest the possibility that SpyB activity is regulated by heme.

Research Organization:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
FG02-93ER20097
OSTI ID:
1365842
Journal Information:
Frontiers in Cellular and Infection Microbiology, Vol. 6; ISSN 2235-2988
Publisher:
Frontiers Research FoundationCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

References (66)

Identification of SpyA, a novel ADP-ribosyltransferase of Streptococcus pyogenes: Identification of SpyA journal August 2004
Identification and Characterization of a Novel Heme-Associated Cell Surface Protein Made by Streptococcus pyogenes journal August 2002
The GAS PefCD exporter is a MDR system that confers resistance to heme and structurally diverse compounds journal April 2016
Cofacial Heme Binding is Linked to Dimerization by a Bacterial Heme Transport Protein journal October 2006
Simultaneous determination of hemes a, b, and c from pyridine hemochrome spectra journal February 1987
Synthetic Lethal Compound Combinations Reveal a Fundamental Connection between Wall Teichoic Acid and Peptidoglycan Biosyntheses in Staphylococcus aureus journal November 2010
The global burden of group A streptococcal diseases journal November 2005
An assessment of methanolysis and other factors used in the analysis of carbohydrate-containing materials journal December 1971
The crimson conundrum: heme toxicity and tolerance in GAS journal November 2014
Attenuation of penicillin resistance in a peptidoglycan O-acetyl transferase mutant of Streptococcus pneumoniae journal September 2006
Characterization of the Linkage between the Type III Capsular Polysaccharide and the Bacterial Cell Wall of Group B Streptococcus journal March 2000
Evolutionary Origin and Emergence of a Highly Successful Clone of Serotype M1 Group A Streptococcus Involved Multiple Horizontal Gene Transfer Events journal September 2005
[1] Carbohydrate composition analysis of glycoconjugates by gas-liquid chromatography/mass spectrometry book January 1994
Mechanisms of intrinsic resistance to antimicrobial peptides of Edwardsiella ictaluri and its influence on fish gut inflammation and virulence journal July 2013
A biological price of antibiotic resistance: major changes in the peptidoglycan structure of penicillin-resistant pneumococci. journal July 1990
An improved staining procedure for the detection of the peroxidase activity of cytochrome P-450 on sodium dodecyl sulfate polyacrylamide gels journal September 1976
Shr of group A streptococcus is a new type of composite NEAT protein involved in sequestering haem from methaemoglobin: Haem uptake and reduction by Shr journal September 2010
The Extracellular Heme-binding Protein HbpS from the Soil Bacterium Streptomyces reticuli Is an Aquo-cobalamin Binder journal October 2014
PlyC: A multimeric bacteriophage lysin journal July 2006
Compensatory Evolution of pbp Mutations Restores the Fitness Cost Imposed by β-Lactam Resistance in Streptococcus pneumoniae journal February 2011
Selective Penicillin-Binding Protein Imaging Probes Reveal Substructure in Bacterial Cell Division journal August 2012
Profiling of β-Lactam Selectivity for Penicillin-Binding Proteins in Streptococcus pneumoniae D39 journal April 2015
Role of the Group B Antigen of Streptococcus agalactiae: A Peptidoglycan-Anchored Polysaccharide Involved in Cell Wall Biogenesis journal June 2012
Structure of the streptococcal groups A, A-variant and C carbohydrates journal November 1978
Characterization of a Hemophore-like Protein from Porphyromonas gingivalis journal October 2010
Sortase A localizes to distinct foci on the Streptococcus pyogenes membrane journal November 2008
Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae journal March 2012
Bacterial glycobiology: rhamnose-containing cell wall polysaccharides in Gram-positive bacteria journal March 2016
GacA is essential for Group A S treptococcus and defines a new class of monomeric dTDP-4-dehydrorhamnose reductases (RmlD): GacA is an essential monomeric RmlD enzyme journal October 2015
Wall Teichoic Acid Function, Biosynthesis, and Inhibition journal November 2009
Small Proteins Can No Longer Be Ignored journal June 2014
Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes journal April 2000
Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix journal August 2015
Characterization of Heme-deficient Neuronal Nitric-oxide Synthase Reveals a Role for Heme in Subunit Dimerization and Binding of the Amino Acid Substrate and Tetrahydrobiopterin journal March 1996
Isolation and analysis of cell wall components from Streptococcus pneumoniae journal February 2012
Speciation of Ferriprotoporphyrin IX in Aqueous and Mixed Aqueous Solution Is Controlled by Solvent Identity, pH, and Salt Concentration journal August 2009
Identification and Characterization of a Streptococcus pyogenes Operon Involved in Binding of Hemoproteins and Acquisition of Iron journal March 2003
NikA Binds Heme:  A New Role for an Escherichia coli Periplasmic Nickel-Binding Protein journal May 2007
SpyA is a membrane-bound ADP-ribosyltransferase of Streptococcus pyogenes which modifies a streptococcal peptide, SpyB: SpyA, a membrane enzyme, modifies a peptide, SpyB journal January 2012
Assembly of the Type II Secretion System such as Found in Vibrio cholerae Depends on the Novel Pilotin AspS journal January 2013
Heme is involved in microRNA processing journal December 2006
Colorimetric Method for Determination of Sugars and Related Substances journal March 1956
The chemistry and biochemistry of heme c: functional bases for covalent attachment journal January 2008
Role of staphylococcal wall teichoic acid in targeting the major autolysin Atl journal February 2010
The S treptococcus pyogenes orphan protein tyrosine phosphatase, SP-PTP, possesses dual specificity and essential virulence regulatory functions: Role of LMW SP-PTP in S. pyogenes virulence journal May 2015
Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme journal March 2001
The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design journal June 2014
[26] Genetic manipulation of pathogenic streptococci book January 1991
Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus journal October 2010
Two Group A Streptococcal Peptide Pheromones Act through Opposing Rgg Regulators to Control Biofilm Development journal August 2011
The Elongation of Ovococci journal June 2014
FemA, a host-mediated factor essential for methicillin resistance in Staphylococcus aureus: Molecular cloning and characterization journal October 1989
Characterization of the group A streptococcal polysaccharide by two-dimensional 1H-nuclear-magnetic-resonance spectroscopy journal November 1986
Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor journal July 2010
Hemin Binds to Human Cytoplasmic Arginyl-tRNA Synthetase and Inhibits Its Catalytic Activity journal October 2010
Role of Serine/Threonine Phosphatase (SP-STP) in Streptococcus pyogenes Physiology and Virulence journal September 2011
PpsR, a Regulator of Heme and Bacteriochlorophyll Biosynthesis, Is a Heme-sensing Protein journal February 2012
Molecular and Biological Characterization of Streptococcal SpyA-mediated ADP-ribosylation of Intermediate Filament Protein Vimentin journal May 2012
RivR Is a Negative Regulator of Virulence Factor Expression in Group A Streptococcus journal November 2012
SpyA, a C3-Like ADP-Ribosyltransferase, Contributes to Virulence in a Mouse Subcutaneous Model of Streptococcus pyogenes Infection journal March 2011
Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements journal October 2014
Identification and Characterization of HtsA, a Second Heme-Binding Protein Made by Streptococcus pyogenes journal September 2003
Distribution of the Mosaic StructuredmurM Genes among Natural Populations ofStreptococcus pneumoniae journal December 2000
Precise Deletion of tagD and Controlled Depletion of Its Product, Glycerol 3-Phosphate Cytidylyltransferase, Leads to Irregular Morphology and Lysis of Bacillus subtilisGrown at Physiological Temperature journal November 2001
A Group A Streptococcus ADP-Ribosyltransferase Toxin Stimulates a Protective Interleukin 1β-Dependent Macrophage Immune Response journal March 2015
The Epidemic of Extended-Spectrum-β-Lactamase-Producing Escherichia coli ST131 Is Driven by a Single Highly Pathogenic Subclone, H30-Rx journal December 2013

Cited By (4)

The molecular mechanism of N -acetylglucosamine side-chain attachment to the Lancefield group A carbohydrate in Streptococcus pyogenes journal October 2017
Genome sequence analysis of emm89 Streptococcus pyogenes strains causing infections in Scotland, 2010–2016 journal December 2017
An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins journal June 2019
The molecular mechanism of N-acetylglucosamine side-chain attachment to the Lancefield group A Carbohydrate in Streptococcus pyogenes journal October 2017