title: SpyB, a Small Heme-Binding Protein, Affects the Composition of the Cell Wall inStreptococcus pyogenes.
abstract: Streptococcus pyogenes(Group AStreptococcusor 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 thespyBAoperon, 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 aspyBdeletion 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 thespyBmutant 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. Thus, our data suggest the possibility that SpyB activity is regulated by heme.
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky Lexington, KY, USA.
authors: Rebecca J
authors: RJ
authors: Edgar
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky Lexington, KY, USA.
authors: Jing
authors: J
authors: Chen
authors: Department of Pathology, Ohio State University Columbus, OH, USA.
authors: Sashi
authors: S
authors: Kant
authors: Department of Microbiology, University of Washington Seattle, WA, USA.
authors: Elena
authors: E
authors: Rechkina
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky Lexington, KY, USA.
authors: Jeffrey S
authors: JS
authors: Rush
authors: Complex Carbohydrate Research Center, University of Georgia Athens, GA, USA.
authors: Lennart S
authors: LS
authors: Forsberg
authors: Complex Carbohydrate Research Center, University of Georgia Athens, GA, USA.
authors: Bernhard
authors: B
authors: Jaehrig
authors: Complex Carbohydrate Research Center, University of Georgia Athens, GA, USA.
authors: Parastoo
authors: P
authors: Azadi
authors: Department of Microbiology, University of Washington Seattle, WA, USA.
authors: Veronika
authors: V
authors: Tchesnokova
authors: Department of Microbiology, University of Washington Seattle, WA, USA.
authors: Evgeni V
authors: EV
authors: Sokurenko
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky Lexington, KY, USA.
authors: Haining
authors: H
authors: Zhu
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky Lexington, KY, USA.
authors: Konstantin V
authors: KV
authors: Korotkov
authors: Department of Pathology, Ohio State University Columbus, OH, USA.
authors: Vijay
authors: V
authors: Pancholi
authors: Department of Molecular and Cellular Biochemistry, University of Kentucky Lexington, KY, USA.
authors: Natalia
authors: N
authors: Korotkova
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002473:Cell Wall / Q000737:chemistry*; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D006027:Glycosides / Q000032:analysis; D006418:Heme / Q000378:metabolism; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000235:genetics* / Q000378:metabolism*; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000032:analysis; D010457:Peptidoglycan / Q000032:analysis; D011485:Protein Binding; D055503:Protein Multimerization; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D006027:Glycosides; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D010457:Peptidoglycan; D047090:beta-Lactams; D006418:Heme; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: ADP-ribosyltransferase; Group A carbohydrate; SpyA; SpyB; Streptococcus pyogenes; cell wall; heme