ArticleInfection and immunity2012
Subtilase cytotoxin enhances Escherichia coli survival in macrophages by suppression of nitric oxide production through the inhibition of NF-κB activation.
Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Gut Commensal Klebsiella pneumoniae Extracellular Vesicles Shape a Liver Microenvironment Conducive to Gut-Liver Bacterial Translocation and Pro-Tumorigenic Processes.Journal of extracellular vesicles · 2026Article
- Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification.Nanomaterials (Basel, Switzerland) · 2022Article
- Subtilase cytotoxin from Shiga-toxigeniciScience · 2022Article
- A novel endoplasmic stress mediator, Kelch domain containing 7B (KLHDC7B), increased Harakiri (HRK) in the SubAB-induced apoptosis signaling pathway.Cell death discovery · 2021Article
- Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome.Toxins · 2021Article
- Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival.Scientific reports · 2020Article
- Myocardin-Related Transcription Factor A Mediates LPS-Induced iNOS Transactivation.Inflammation · 2020Article
- Characterization of MDCK cells and evaluation of their ability to respond to infectious and non-infectious stressors.Cytotechnology · 2020Article
- Mechanism of inhibition of Shiga-toxigenicCell death discovery · 2018Article
- TLR2 signal influences the iNOS/NO responses and worm development in C57BL/6J mice infected with Clonorchis sinensis.Parasites & vectors · 2017Article
- Effects of meglumine cyclic adenylate pretreatment on systemic inflammatory response syndrome induced by lipopolysaccharide in rats.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Article
- Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity.The Journal of biological chemistry · 2016Article
- TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4.Free radical biology & medicine · 2016Article
- Subtilase cytotoxin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli induces stress granule formation.Cellular microbiology · 2016Article
- DAP1, a negative regulator of autophagy, controls SubAB-mediated apoptosis and autophagy.Infection and immunity · 2014Article
- Uptake of Shiga-toxigenic Escherichia coli SubAB by HeLa cells requires an actin- and lipid raft-dependent pathway.Cellular microbiology · 2014Article
- Inhibitory effect of citrinin on lipopolisaccharide-induced nitric oxide production by mouse macrophage cells.Mycotoxin research · 2013Article
- Molecular analysis of subtilase cytotoxin genes of food-borne Shiga toxin-producing Escherichia coli reveals a new allelic subAB variant.BMC microbiology · 2013Article
- Recent advances in understanding enteric pathogenic Escherichia coli.Clinical microbiology reviews · 2013Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenic Escherichia coli (STEC), cleaves an endoplasmic reticulum (ER) chaperone, BiP/Grp78, leading to induction of ER stress and caspase-dependent apoptosis. SubAB alters the innate immune response. SubAB pretreatment of macrophages inhibited lipopolysaccharide (LPS)-induced production of both monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor α (TNF-α). We investigated here the mechanism by which SubAB inhibits nitric oxide (NO) production by mouse macrophages. SubAB suppressed LPS-induced NO production through inhibition of inducible NO synthase (iNOS) mRNA and protein expression. Further, SubAB inhibited LPS-induced IκB-α phosphorylation and nuclear localization of the nuclear factor-κB (NF-κB) p65/p50 heterodimer. Reporter gene and chromatin immunoprecipitation (ChIP) assays revealed that SubAB reduced LPS-induced NF-κB p65/p50 heterodimer binding to an NF-κB binding site on the iNOS promoter. In contrast to the native toxin, a catalytically inactivated SubAB mutant slightly enhanced LPS-induced iNOS expression and binding of NF-κB subunits to the iNOS promoter. The SubAB effect on LPS-induced iNOS expression was significantly reduced in macrophages from NF-κB1 (p50)-deficient mice, which lacked a DNA-binding subunit of the p65/p50 heterodimer, suggesting that p50 was involved in SubAB-mediated inhibition of iNOS expression. Treatment of macrophages with an NOS inhibitor or expression of SubAB by E. coli increased E. coli survival in macrophages, suggesting that NO generated by macrophages resulted in efficient killing of the bacteria and SubAB contributed to E. coli survival in macrophages. Thus, we hypothesize that SubAB might represent a novel bacterial strategy to circumvent host defense during STEC infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.