Induction of endoplasmic reticulum stress and unfolded protein response constitutes a pathogenic strategy of group A streptococcus.
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.
['Baruch|Moshe|M|', 'Hertzog|Baruch B|BB|', 'Ravins|Miriam|M|', 'Anand|Aparna|A|', 'Cheng|Catherine Youting|CY|', 'Biswas|Debabrata|D|', 'Tirosh|Boaz|B|', 'Hanski|Emanuel|E|']
D000818:Animals D001216:Asparagine D001426:Bacterial Proteins D059865:Endoplasmic Reticulum Stress D054884:Host-Pathogen Interactions D006801:Humans D013290:Streptococcal Infections D013297:Streptococcus pyogenes D013301:Streptolysins D056811:Unfolded Protein Response
group A streptococcus UPR asparagine asparaginase metabolism virulence