A potential therapeutic peptide-based neutralizer that potently inhibits Shiga toxin 2 in vitro and in vivo

Scientific Reports
Tao LiHui Wang

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 a...Continue Reading

References

Jan 1, 1997·ILAR Journal·J. Derrell ClarkDennis F. Kohn
Nov 28, 2001·The Journal of Biological Chemistry·Anna M SoltykJames L Brunton
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kiyotaka NishikawaYasuhiro Natori
Jan 28, 2004·The Journal of Infectious Diseases·Miho WatanabeKiyotaka Nishikawa
Apr 13, 2004·The Journal of Biological Chemistry·Marie E FraserMichael N G James
Jul 21, 2004·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·V Pistone CreydtC Ibarra
Mar 23, 2005·Lancet·Phillip I TarrWayne L Chandler
Sep 20, 2005·Bioorganic & Medicinal Chemistry·Yoshinao YamadaKazukiyo Kobayashi
Apr 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sharon X WenAlison D O'Brien
Oct 27, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kiyotaka NishikawaYasuhiro Natori
Oct 28, 2008·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Mini MichaelElisabeth M Hodson
Dec 22, 2009·Nature Reviews. Microbiology·Ludger Johannes, Winfried Römer
May 31, 2011·Nucleic Acids Research·Nir LondonOra Schueler-Furman
Jun 24, 2011·The New England Journal of Medicine·Christina FrankUNKNOWN HUS Investigation Team
Nov 10, 2011·Toxins·Stephanie Schüller
Aug 29, 2012·EMBO Molecular Medicine·Helge KarchMiguel Vicente
Sep 11, 2012·Toxicon : Official Journal of the International Society on Toxinology·Jonas BerganKirsten Sandvig
Sep 19, 2012·Nature Reviews. Nephrology·Howard TrachtmanRolf A K Stahl

❮ Previous
Next ❯

Citations

Aug 22, 2018·Current Drug Metabolism·Lin NingJian Huang
Jun 30, 2018·Current Medicinal Chemistry·Bifang HeJian Huang
Dec 22, 2017·Signal Transduction and Targeted Therapy·Yuan ZhangXun Xu
Jan 25, 2020·Toxins·Adrien JosephAlexandre Hertig
Apr 21, 2017·Emerging Topics in Life Sciences·Alejandro Huerta-Uribe, Andrew J Roe

❮ Previous
Next ❯

Methods Mentioned

BETA
phage display
enzyme-linked immunosorbent assay
ELISA
peptide folding

Software Mentioned

FOLD
FlexPepDock
AMBER09
DAS
ZDOCK
PEP

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.