title: Cellular aspects of the distinct M protein and SfbI anchoring pathways in Streptococcus pyogenes.
abstract: Wall-anchored surface proteins are critical for the in vivo survival of Streptococcus pyogenes. Cues in the signal sequence direct the membrane translocation of surface proteins: M protein to the septum, and SfbI to the poles. Both proteins are subsequently anchored to the wall by the membrane bound enzyme sortase A. However, the cellular features of these pathways are not fully understood. Here we show that M protein and SfbI are anchored simultaneously throughout the cell cycle. M protein is rapidly anchored at the septum, and in part of the cell cycle, is anchored simultaneously at the mother and daughter septa. Conversely, SfbI accumulates gradually on peripheral peptidoglycan, resulting in a polar distribution. Sortase is not required for translocation of M protein or SfbI at their respective locations. Methicillin-induced unbalanced peptidoglycan synthesis diminishes surface M protein but not SfbI. Furthermore, overexpression of the division regulator DivIVA also diminishes surface M protein but increases SfbI. These results demonstrate a close connection between the regulation of cell division and protein anchoring. Better understanding of the spatial regulation of surface anchoring may lead to the identification of novel targets for the development of anti-infective agents, given the importance of surface molecules for pathogenesis.
authors.affiliation: Bacterial Pathogenesis and Immunology, Rockefeller University, New York, USA. araz@rockefeller.edu
authors.forename: Assaf
authors.initials: A
authors.lastname: Raz
authors.forename: Susanne R
authors.initials: SR
authors.lastname: Talay
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D019881:Aminoacyltransferases / Q000378:metabolism; D000942:Antigens, Bacterial / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010457:Peptidoglycan; C078635:fibronectin-binding proteins, bacterial; C014689:streptococcal M protein; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases