title: Serine/threonine phosphatase (SP-STP), secreted from Streptococcus pyogenes, is a pro-apoptotic protein.
abstract: This investigation illustrates an important property of eukaryote-type serine/threonine phosphatase (SP-STP) of group A Streptococcus (GAS) in causing programmed cell death of human pharyngeal cells. The secretory nature of SP-STP, its elevated expression in the intracellular GAS, and the ability of wild-type GAS but not the GAS mutant devoid of SP-STP to cause apoptosis of the host cell both in vitro and in vivo suggest that GAS deploys SP-STP as an important virulence determinant to exploit host cell machinery for its own advantage during infection. The exogenously added SP-STP is able to enter the cytoplasm and subsequently traverses into the nucleus in a temporal fashion to cause apoptosis of the pharyngeal cells. The programmed cell death induced by SP-STP, which requires active transcription and de novo protein synthesis, is also caspase-dependent. Furthermore, the entry of SP-STP into the cytoplasm is dependent on its secondary structure as the catalytically inactive SP-STP with an altered structure is unable to internalize and cause apoptosis. The ectopically expressed wild-type SP-STP was found to be in the nucleus and conferred apoptosis of Detroit 562 pharyngeal cells. However, the catalytically inactive SP-STP was unable to cause apoptosis even when intracellularly expressed. The ability of SP-STP to activate pro-apoptotic signaling cascades both in the cytoplasm and in the nucleus resulted in mitochondrial dysfunctioning and perturbation in the phosphorylation status of histones in the nucleus. SP-STP thus not only functions as a virulence regulator but also as an important factor responsible for host-related pathogenesis.
authors.affiliation: Department of Pathology, Ohio State University College of Medicine, Columbus, Ohio 43210-1214, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Agarwal
authors.forename: Shivangi
authors.initials: S
authors.lastname: Agarwal
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Preeti
authors.initials: P
authors.lastname: Pancholi
authors.forename: Vijay
authors.initials: V
authors.lastname: Pancholi
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051379:Mice; D010608:Pharyngeal Diseases / Q000382:microbiology / Q000503:physiopathology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology* / Q000503:physiopathology*; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence
chemical_list: D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D010749:Phosphoprotein Phosphatases