title: A potential therapeutic peptide-based neutralizer that potently inhibits Shiga toxin 2 in vitro and in vivo.
abstract: Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which can cause serious clinical complications in humans, such as hemolytic uremic syndrome (HUS). Recently, we screened and identified two peptide-based Stx2 neutralizers, TF-1 and WA-8, which specifically and directly bind to Stx2. Computer simulations suggested that the majority of TF-1 or WA-8 binds tightly at the receptor-binding site 3 of Stx2. The two peptides also effectively inhibited the cytotoxic activity of Stx2 by blocking the binding of Stx2 to target cells. TF-1 exhibits remarkable therapeutic potency in both mice and rat toxicity models. In mice toxicity models, TF-1 provided full protection when mice were injected with 5 LD50 of Stx2. In rat toxicity models, TF-1 reduced fatal tissue damage and completely protected rats from the lethal challenges of Stx2. In these rats, TF-1 significantly decreased the concentration of Stx2 in blood and diminished tissue distribution levels of Stx2. Furthermore, TF-1 effectively protected rats from the pathological effects caused by Stx2, especially in the kidney, thymus, adrenal gland, and lung. Taken together, these results indicate that TF-1 is a promising therapeutic agent against the pathogenicity of Stx2.
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Yuenan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, China.|Center for Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Nianzhi
authors.initials: N
authors.lastname: Ning
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology, Beijing Xuanwu Hospital, Beijing, People's Republic of China.
authors.forename: Shenghan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, China.|Center for Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.|Guangxi Medical University, Nanning, PR China.|Department of Microbiology, Anhui Medical University, Hefei, 230032, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000595:Amino Acid Sequence; D000818:Animals; D000931:Antidotes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054324:Enterohemorrhagic Escherichia coli / Q000737:chemistry* / Q000378:metabolism / Q000472:pathogenicity; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity; D016019:Survival Analysis; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity
chemical_list: D000931:Antidotes; D019151:Peptide Library; D010455:Peptides; D011994:Recombinant Proteins; D022641:Shiga Toxin 2; D037521:Virulence Factors