[ODP6B] b. Toxins, Effectors, and Bioactive Substances

[ODP-128] SubAB induces a novel form of Lipocalin 2, which involves in STEC survival

○Kinnosuke Yahiro¹, Kohei Ogura², Yoshiyuki Goto³, Sunao Iyoda⁴, Makoto Ohnishi⁴ (¹Dept. Molecular Infectiology, Grad. Sch. Medicine, Chiba Univ., ²Advanced Health Care Science Research Unit, Institute for Frontier Science Initiative, Kanazawa Univ., ³Div. Molecular Immunology, Medical Mycology Research Center, Chiba Univ., ⁴Dept. Bacteriology I, National Institute of Infectious Diseases)

Shiga-toxigenic Escherichia coli (STEC) infection causes severe bloody diarrhea, renal failure, and hemolytic uremic syndrome (HUS). 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. Here, we demonstrates 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 PERK via CHOP 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.