Journal article

Publication year: 2012

Pages: 949-964

Journal: Cellular Microbiology

Volume number: 14

Issue number: 6

ISSN: 1462-5814

eISSN: 1462-5822

DOI Link: https://doi.org/10.1111/j.1462-5822.2012.01769.x

Publisher: Wiley

Abstract: 
The endoplasmic reticulum (ER) responds to perturbation of homeostasis with stress. To maintain ER function, a signalling-circuitry has evolved which, when engaged, attempts to reduce a surplus of unfolded proteins by triggering the unfolded protein response (UPR). Several studies have implicated UPR in viral infections, neurodegenerative disorders and metabolic diseases but UPR has not yet been widely linked to bacterial infections. Here we demonstrate that the facultative intracellular pathogen Listeria monocytogenes (Lm) induces ER expansion and UPR prior to host cell entry. Lm activated protein kinase RNA-like ER kinase (PERK) evidenced by the phosphorylation of the a-subunit of eukaryotic translation initiation factor-2 (eIF2a), inositol-requiring protein-1 (IRE1) as shown by detection of spliced X-box binding protein-1 (XBP1) and activating transcription factor-6 (ATF6) as demonstrated by depletion of its inactive form. A mutant Lm?hly strain that did not produce listeriolysin (LLO) lacked the UPR response. Conversely purified LLO activated UPR. Sustained infection with Lm resulted in apoptosis. Induction of ER stress by thapsigargin or tunicamycin reduced intracellular bacterial number. Our findings suggest that UPR plays an important role in the cell autonomous defence responses to bacterial infection.

Harvard Citation style: Pillich, H., Loose, M., Zimmer, K. and Chakraborty, T. (2012) Activation of the unfolded protein response by Listeria monocytogenes, Cellular Microbiology, 14(6), pp. 949-964. https://doi.org/10.1111/j.1462-5822.2012.01769.x

APA Citation style: Pillich, H., Loose, M., Zimmer, K., & Chakraborty, T. (2012). Activation of the unfolded protein response by Listeria monocytogenes. Cellular Microbiology. 14(6), 949-964. https://doi.org/10.1111/j.1462-5822.2012.01769.x