title: Induction of endoplasmic reticulum stress and unfolded protein response constitutes a pathogenic strategy of group A streptococcus.
abstract: The connection between bacterial pathogens and unfolded protein response (UPR) is poorly explored. In this review we highlight the evidence showing that group A streptococcus (GAS) induces endoplasmic reticulum (ER) stress and UPR through which it captures the amino acid asparagine (ASN) from the host. GAS acts extracellularly and during adherence to host cells it delivers the hemolysin toxins; streptolysin O (SLO) and streptolysin S (SLS). By poorly understood pathways, these toxins trigger UPR leading to the induction of the transcriptional regulator ATF4 and consequently to the upregulation of asparagine synthetase (ASNS) transcription leading to production and release of ASN. GAS senses ASN and alters gene expression profile accordingly, and increases the rate of multiplication. We suggest that induction of UPR by GAS and by other bacterial pathogens represent means through which bacterial pathogens gain nutrients from the host, obviating the need to become internalized or inflict irreversible cell damage.
authors.affiliation: Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem (HUJI) Jerusalem, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Baruch
authors.affiliation: Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem (HUJI) Jerusalem, Israel.
authors.forename: Baruch B
authors.initials: BB
authors.lastname: Hertzog
authors.affiliation: Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem (HUJI) Jerusalem, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ravins
authors.affiliation: Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem (HUJI) Jerusalem, Israel.
authors.forename: Aparna
authors.initials: A
authors.lastname: Anand
authors.affiliation: Department of Microbiology, Center for Research Excellence and Technological Enterprise (CREATE), National University of Singapore (NUS) and NUS-HUJI Singapore.
authors.forename: Catherine Youting
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem (HUJI) Jerusalem, Israel ; Department of Microbiology, Center for Research Excellence and Technological Enterprise (CREATE), National University of Singapore (NUS) and NUS-HUJI Singapore.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Biswas
authors.affiliation: The School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem Jerusalem, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Tirosh
authors.affiliation: Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem (HUJI) Jerusalem, Israel ; Department of Microbiology, Center for Research Excellence and Technological Enterprise (CREATE), National University of Singapore (NUS) and NUS-HUJI Singapore.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Hanski
mesh_terms: D000818:Animals; D001216:Asparagine / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D054884:Host-Pathogen Interactions; D006801:Humans; D013290:Streptococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000502:physiology*; D013301:Streptolysins / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O; C026050:streptolysin S; D001216:Asparagine
keywords: UPR; asparaginase; asparagine; group A streptococcus; metabolism; virulence