Abstract

Shiga-toxigenic Escherichia coli (STEC) infection causes severe bloody diarrhea, renal failure, and hemolytic uremic syndrome. Recent studies showed global increases in Locus for Enterocyte Effacement (LEE)-negative STEC infection. Some LEE-negative STEC produce Subtilase cytotoxin (SubAB), which cleaves endoplasmic reticulum (ER) chaperone protein BiP, inducing ER stress and apoptotic cell death. In this study, we report that SubAB induces expression of a novel form of Lipocalin-2 (LCN2), and describe its biological activity and effects on apoptotic cell death. SubAB induced expression of a novel LCN2, which was regulated by PRKR-like endoplasmic reticulum kinase via the C/EBP homologous protein pathway. SubAB-induced novel-sized LCN2 was not secreted into the culture supernatant. Increased intracellular iron level by addition of holo-transferrin or FeCl3 suppressed SubAB-induced PARP cleavage. Normal-sized FLAG-tagged LCN2 suppressed STEC growth, but this effect was not seen in the presence of SubAB- or tunicamycin-induced unglycosylated FLAG-tagged LCN2. Our study demonstrates that SubAB-induced novel-sized LCN2 does not have anti-STEC activity, suggesting that SubAB plays a crucial role in the survival of LEE-negative STEC as well as inducing apoptosis of the host cells.

Details

Title
Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival
Author
Yahiro Kinnosuke 1 ; Ogura Kohei 2 ; Goto Yoshiyuki 3 ; Iyoda Sunao 4 ; Kobayashi Tatsuya 5 ; Takeuchi Hiroki 6 ; Ohnishi Makoto 4 ; Moss, Joel 7 

 Chiba University, Department of Molecular Infectiology, Graduate School of Medicine, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101) 
 Kanazawa University, Advanced Health Care Science Research Unit, Institute for Frontier Science Initiative, Kanazawa, Japan (GRID:grid.9707.9) (ISNI:0000 0001 2308 3329) 
 Chiba University, Division of Molecular Immunology, Medical Mycology Research Center, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101); The University of Tokyo, Division of Mucosal Symbiosis, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); AMED-PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan (GRID:grid.480536.c) (ISNI:0000 0004 5373 4593) 
 National Institute of Infectious Diseases, Department of Bacteriology I, Tokyo, Japan (GRID:grid.410795.e) (ISNI:0000 0001 2220 1880) 
 Chiba University, Reproductive Medicine, Graduate School of Medicine, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101) 
 University of Tsukuba Hospital, Clinical Laboratory, Tsukuba, Japan (GRID:grid.412814.a) (ISNI:0000 0004 0619 0044) 
 National Institutes of Health, Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2471532190
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.