Selective Evolution of Ligands by Exponential Enrichment to Identify RNA Aptamers against Shiga Toxins

Challa, Sreerupa; Tzipori, Saul; Sheoran, Abhineet S.

doi:10.1155/2014/214929

Cited by 15 publications

(9 citation statements)

References 38 publications

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“…To treat bacterial infection, functional aptamers have been selected to bind with antigens (25), toxins (26,27), drug-resistant enzymes (28), and cells (29) of pathogenic bacteria. Here, we report the creation of a functional aptamer that can inhibit SEB superantigen activity.…”

Section: Discussionmentioning

confidence: 99%

Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

Wang

Gan

Jiang

et al. 2015

Antimicrob Agents Chemother

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c Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (K d ‫؍‬ 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a "double-hit" mouse model of SEB-induced TSS, established via sensitization with D-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS.

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Section: Discussionmentioning

confidence: 99%

Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

Wang

Gan

Jiang

et al. 2015

Antimicrob Agents Chemother

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“…After five rounds of selection, significant enrichment of aptamer pool was obtained against Stx2, but not against Stx1. However, none of the aptamers neutralized Stx2-mediated cytotoxicity and death of HeLa cells (Challa et al 2014).…”

Section: Shiga Toxinsmentioning

confidence: 94%

“…Toxins consisting of an A-subunit monomer and a B-subunit pentamer bind to cell surface receptors. The internalization of catalytically active A-subunit delivered to cytosol via retrograde transport causes shut down of protein synthesis and leads to cell death (Challa et al 2014). Nucleic acid aptamers are being developed as therapeutic and diagnostic reagents against biotoxins.…”

Section: Shiga Toxinsmentioning

confidence: 99%

Current advances in aptamer-assisted technologies for detecting bacterial and fungal toxins

et al. 2018

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SummaryInfectious diseases are among the common leading causes of morbidity and mortality worldwide. Associated with the emergence of new infectious diseases, the increasing number of antimicrobial-resistant isolates presents a serious threat to public health and hospitalized patients. A microbial pathogen may elicit several host responses and use a variety of mechanisms to evade host defences. These methods and mechanisms include capsule, lipopolysaccharides or cell wall components, adhesions and toxins. Toxins inhibit phagocytosis, cause septic shock and host cell damages by binding to host surface receptors and invasion. Bacterial and fungal pathogens are able to apply many different toxin-dependent mechanisms to disturb signalling pathways and the structural integrity of host cells for establishing and maintaining infections Initial techniques for analysis of bacterial toxins were based on in vivo or in vitro assessments. There is a permanent demand for appropriate detection methods which are affordable, practical, careful, rapid, sensitive, efficient and economical. Aptamers are DNA or RNA oligonucleotides that are selected by systematic evolution of ligands using exponential enrichment (SELEX) methods and can be applied in diagnostic applications. This review provides an overview of aptamer-based methods as a novel approach for detecting toxins in bacterial and fungal pathogens.

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“…We examined the effects of BAI on cell toxicity of Stx2 with HeLa cells as described previously (23). HeLa cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 3 mM glutamine, antibiotics (100 U/ml penicillin and 100 U/ml streptomycin), and 10% heat-inactivated fetal bovine serum, at 37°C in 5% CO 2 in a humidified incubator.…”

Section: Methodsmentioning

confidence: 99%

Baicalin Inhibits the Lethality of Shiga-Like Toxin 2 in Mice

Dong

Zhang

Niu

et al. 2015

Antimicrob Agents Chemother

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e Shiga-like toxins (Stxs), produced by pathogenic Escherichia coli, are a major virulence factor involved in severe diseases in human and animals. These toxins are ribosome-inactivating proteins, and treatment for diseases caused by them is not available. Therefore, there is an urgent need for agents capable of effectively targeting this lethal toxin. In this study, we identified baicalin, a flavonoid compound used in Chinese traditional medicine, as a compound against Shiga-like toxin 2 (Stx2). We found that baicalin significantly improves renal function and reduces Stx2-induced lethality in mice. Further experiments revealed that baicalin induces the formation of oligomers by the toxin by direct binding. We also identified the residues important for such interactions and analyzed their roles in binding baicalin by biophysical and biochemical analyses. Our results establish baicalin as a candidate compound for the development of therapeutics against diseases caused by Stxs.

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Selective Evolution of Ligands by Exponential Enrichment to Identify RNA Aptamers against Shiga Toxins

Cited by 15 publications

References 38 publications

Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

Current advances in aptamer-assisted technologies for detecting bacterial and fungal toxins

Baicalin Inhibits the Lethality of Shiga-Like Toxin 2 in Mice

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