scholarly journals Immunomodulatory Activity of Recombinant Ricin Toxin Binding Subunit B (RTB)

2013 ◽  
Vol 14 (6) ◽  
pp. 12401-12410 ◽  
Author(s):  
Wensen Liu ◽  
Na Xu ◽  
Hongyan Yuan ◽  
Songyan Li ◽  
Linna Liu ◽  
...  
Keyword(s):  
Immunomodulatory Activity ◽  
Ricin Toxin ◽  
Toxin Binding ◽  
Subunit B ◽  
Binding Subunit

TLR4-mediated activation of mouse macrophages by recombinant ricin toxin binding subunit B (RTB)

Toxicon ◽  
2019 ◽  
Vol 158 ◽  
pp. S71-S72
Author(s):  
Na Xu ◽  
Wenhe Zhu ◽  
Ying Chen ◽  
YanWang ◽  
Letian Li ◽  
...  
Keyword(s):  
Ricin Toxin ◽  
Toxin Binding ◽  
Mouse Macrophages ◽  
Subunit B ◽  
Binding Subunit

Hybrids of carbon dots with subunit B of ricin toxin for enhanced immunomodulatory activity

2018 ◽  
Vol 523 ◽  
pp. 226-233 ◽  
Author(s):  
Yawei Li ◽  
Wensen Liu ◽  
Chengbiao Sun ◽  
Min Zheng ◽  
Jianxu Zhang ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Immunomodulatory Activity ◽  
Ricin Toxin ◽  
Subunit B

scholarly journals Targeting Macromolecules to CNS and Other Hard-to-Treat Organs Using Lectin-Mediated Delivery

2020 ◽  
Vol 21 (3) ◽  
pp. 971 ◽  
Author(s):  
Walter Acosta ◽  
Carole L. Cramer
Keyword(s):  
Mammalian Cells ◽  
Drug Efficacy ◽  
Carbohydrate Binding ◽  
Lysosomal Storage ◽  
Ricin Toxin ◽  
Biodistribution Studies ◽  
Macromolecular Drugs ◽  
Multiple Routes ◽  
Subunit B

The greatest challenges for therapeutic efficacy of many macromolecular drugs that act on intracellular are delivery to key organs and tissues and delivery into cells and subcellular compartments. Transport of drugs into critical cells associated with disease, including those in organs protected by restrictive biological barriers such as central nervous system (CNS), bone, and eye remains a significant hurdle to drug efficacy and impacts commercial risk and incentives for drug development for many diseases. These limitations expose a significant need for the development of novel strategies for macromolecule delivery. RTB lectin is the non-toxic carbohydrate-binding subunit B of ricin toxin with high affinity for galactose/galactosamine-containing glycolipids and glycoproteins common on human cell surfaces. RTB mediates endocytic uptake into mammalian cells by multiple routes exploiting both adsorptive-mediated and receptor-mediated mechanisms. In vivo biodistribution studies in lysosomal storage disease models provide evidence for the theory that the RTB-lectin transports corrective doses of enzymes across the blood–brain barrier to treat CNS pathologies. These results encompass significant implications for protein-based therapeutic approaches to address lysosomal and other diseases having strong CNS involvement.

scholarly journals A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 215 ◽  
Author(s):  
Yinghui Rong ◽  
Michael Pauly ◽  
Adrian Guthals ◽  
Henry Pham ◽  
Dylan Ehrbar ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mouse Model ◽  
Therapeutic Efficacy ◽  
Lethal Dose ◽  
Immunodominant Epitope ◽  
Ricin Toxin ◽  
Humanized Monoclonal Antibody ◽  
Antibody Cocktail ◽  
Binding Subunit

PB10 IgG1, a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when co-administered with a second MAb, SylH3, targeting RT’s binding subunit (RTB). Here we report that the PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP) in a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to engineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly efficacious in the mouse model, thereby opening the door to future testing in non-human primates.

scholarly journals The Majority of Typhoid Toxin-Positive Salmonella Serovars Encode ArtB, an Alternate Binding Subunit

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
A. Gaballa ◽  
R. A. Cheng ◽  
A. S. Harrand ◽  
A. R. Cohn ◽  
M. Wiedmann
Keyword(s):  
Virulence Factors ◽  
Salmonella Enterica ◽  
Affinity Purification ◽  
Growth Conditions ◽  
Minor Role ◽  
Content Type ◽  
Toxin Binding ◽  
Typhoid Toxin ◽  
Binding Subunit

ABSTRACT Salmonella enterica encodes a wide array of virulence factors. One novel virulence factor, an A2B5 toxin known as the typhoid toxin (TT), was recently identified among a variety of S. enterica serovars. While past studies have shown that some serovars encode both the TT (active subunits CdtB and PltA and binding subunit PltB) and a second binding subunit (ArtB), these serovars were thought to be the exception. Here, we show that genes encoding the TT are detected in more than 100 serovars representing distinct phylogenetic lineages of S. enterica subsp. enterica, although clade B and section Typhi are significantly more likely to encode TT genes than serovars from other clades. Furthermore, we show that 81% of these TT-positive serovars also encode artB, suggesting that the cooccurrence of both toxin binding subunits is considerably more common than previously thought. A combination of in silico modeling, bacterial two-hybrid system screening, and tandem affinity purification (TAP) of toxin subunits suggests that ArtB and PltB interact in vitro, at least under some growth conditions. While different growth conditions yielded slightly higher transcript abundances of artB and pltB, both genes had their highest relative transcript abundances when Salmonella was grown under low-Mg2+ conditions, suggesting that ArtB and PltB may compete for inclusion in the TT. Together, our results suggest that ArtB likely plays an important and previously underappreciated role in the biology of the TT produced by typhoidal and nontyphoidal Salmonella. IMPORTANCE While previous reports had suggested that the typhoid toxin (TT) could potentially use ArtB as an alternate binding subunit, this was thought to play a minor role in the evolution and biology of the toxin. In this study, we establish that both TT genes and artB are widespread among Salmonella enterica subsp. enterica, suggesting that TT likely plays a broader role in Salmonella virulence that extends beyond its proposed role in typhoid fever. Furthermore, our data suggest the selective maintenance of both toxin binding subunits, which may compete for inclusion in the holotoxin. Last, our data support the importance of characterizing diverse nontyphoidal Salmonella (NTS) serovars, as the presence of classically defined typhoidal virulence factors among NTS serovars continues to challenge the typhoid-nontyphoid Salmonella paradigm.

NMR Solution Structure of Subunit F of the Methanogenic A1AOAdenosine Triphosphate Synthase and Its Interaction with the Nucleotide-Binding Subunit B†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (42) ◽  
pp. 11684-11694 ◽  
Author(s):  
Shovanlal Gayen ◽  
Subramanian Vivekanandan ◽  
Goran Biuković ◽  
Gerhard Grüber ◽  
Ho Sup Yoon
Keyword(s):  
Solution Structure ◽  
Nucleotide Binding ◽  
Nmr Solution Structure ◽  
Subunit B ◽  
Binding Subunit
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