Neutralization of staphylococcal enterotoxin B by an aptamer antagonist
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 proc...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy 2015-04, Vol.59 (4), p.2072-2077 |
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| container_issue | 4 |
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| container_title | Antimicrobial agents and chemotherapy |
| container_volume | 59 |
| creator | Wang, Kaiyu Gan, Longjie Jiang, Li Zhang, Xianhui Yang, Xiangyue Chen, Min Lan, Xiaopeng |
| description | 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 (Kd = 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. |
| doi_str_mv | 10.1128/AAC.04414-14 |
| format | Article |
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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 (Kd = 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.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.04414-14</identifier><identifier>PMID: 25624325</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Animals ; Cell Proliferation - drug effects ; Cloning, Molecular ; Computational Biology ; Cytokines - biosynthesis ; Drug Evaluation, Preclinical ; Enterotoxins ; Enterotoxins - antagonists & inhibitors ; Experimental Therapeutics ; Female ; Galactosamine - pharmacology ; Humans ; Mice ; Mice, Inbred BALB C ; Monocytes - drug effects ; SELEX Aptamer Technique ; Shock, Septic - drug therapy ; Shock, Septic - microbiology</subject><ispartof>Antimicrobial agents and chemotherapy, 2015-04, Vol.59 (4), p.2072-2077</ispartof><rights>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</rights><rights>Copyright © 2015, American Society for Microbiology. All Rights Reserved. 2015 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a451t-e25f7c6840b201c557865e828279f9593ffcb0b31392327ef8a824cc8708a26f3</citedby><cites>FETCH-LOGICAL-a451t-e25f7c6840b201c557865e828279f9593ffcb0b31392327ef8a824cc8708a26f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356834/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356834/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25624325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Kaiyu</creatorcontrib><creatorcontrib>Gan, Longjie</creatorcontrib><creatorcontrib>Jiang, Li</creatorcontrib><creatorcontrib>Zhang, Xianhui</creatorcontrib><creatorcontrib>Yang, Xiangyue</creatorcontrib><creatorcontrib>Chen, Min</creatorcontrib><creatorcontrib>Lan, Xiaopeng</creatorcontrib><title>Neutralization of staphylococcal enterotoxin B by an aptamer antagonist</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>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 (Kd = 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.</description><subject>Animals</subject><subject>Cell Proliferation - drug effects</subject><subject>Cloning, Molecular</subject><subject>Computational Biology</subject><subject>Cytokines - biosynthesis</subject><subject>Drug Evaluation, Preclinical</subject><subject>Enterotoxins</subject><subject>Enterotoxins - antagonists & inhibitors</subject><subject>Experimental Therapeutics</subject><subject>Female</subject><subject>Galactosamine - pharmacology</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Monocytes - drug effects</subject><subject>SELEX Aptamer Technique</subject><subject>Shock, Septic - drug therapy</subject><subject>Shock, Septic - microbiology</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1PwzAMhiMEYmNw44x6BImOfDe9II0JBtIEFzhHaUi2Tm0zkhQxfj0dGxMcONmWXz22XwNwiuAQISyuRqPxEFKKaIroHugjmIuUs5zvgz6EnKdUQNoDRyEsYFezHB6CHmYcU4JZH0weTRu9qspPFUvXJM4mIarlfFU57bRWVWKaaLyL7qNskpukWCWqSdQyqtr4Lo1q5poyxGNwYFUVzMk2DsDL3e3z-D6dPk0exqNpqihDMTWY2UxzQWGBIdKMZYIzI7DAWW5zlhNrdQELgkiOCc6MFUpgqrXIoFCYWzIA1xvusi1q86q77brt5dKXtfIr6VQp_3aaci5n7l1SwrggtAOcbwHevbUmRFmXQZuqUo1xbZCIZ5wwAjPYSS83Uu1dCN7Y3RgE5dp72Xkvv72XaE2-2MhVqLFcuNY3nRP_ac9-n7ED_zyGfAFiD4wK</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Wang, Kaiyu</creator><creator>Gan, Longjie</creator><creator>Jiang, Li</creator><creator>Zhang, Xianhui</creator><creator>Yang, Xiangyue</creator><creator>Chen, Min</creator><creator>Lan, Xiaopeng</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20150401</creationdate><title>Neutralization of staphylococcal enterotoxin B by an aptamer antagonist</title><author>Wang, Kaiyu ; Gan, Longjie ; Jiang, Li ; Zhang, Xianhui ; Yang, Xiangyue ; Chen, Min ; Lan, Xiaopeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a451t-e25f7c6840b201c557865e828279f9593ffcb0b31392327ef8a824cc8708a26f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Cell Proliferation - drug effects</topic><topic>Cloning, Molecular</topic><topic>Computational Biology</topic><topic>Cytokines - biosynthesis</topic><topic>Drug Evaluation, Preclinical</topic><topic>Enterotoxins</topic><topic>Enterotoxins - antagonists & inhibitors</topic><topic>Experimental Therapeutics</topic><topic>Female</topic><topic>Galactosamine - pharmacology</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Monocytes - drug effects</topic><topic>SELEX Aptamer Technique</topic><topic>Shock, Septic - drug therapy</topic><topic>Shock, Septic - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Kaiyu</creatorcontrib><creatorcontrib>Gan, Longjie</creatorcontrib><creatorcontrib>Jiang, Li</creatorcontrib><creatorcontrib>Zhang, Xianhui</creatorcontrib><creatorcontrib>Yang, Xiangyue</creatorcontrib><creatorcontrib>Chen, Min</creatorcontrib><creatorcontrib>Lan, Xiaopeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Kaiyu</au><au>Gan, Longjie</au><au>Jiang, Li</au><au>Zhang, Xianhui</au><au>Yang, Xiangyue</au><au>Chen, Min</au><au>Lan, Xiaopeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neutralization of staphylococcal enterotoxin B by an aptamer antagonist</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>59</volume><issue>4</issue><spage>2072</spage><epage>2077</epage><pages>2072-2077</pages><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). 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| subjects | Animals Cell Proliferation - drug effects Cloning, Molecular Computational Biology Cytokines - biosynthesis Drug Evaluation, Preclinical Enterotoxins Enterotoxins - antagonists & inhibitors Experimental Therapeutics Female Galactosamine - pharmacology Humans Mice Mice, Inbred BALB C Monocytes - drug effects SELEX Aptamer Technique Shock, Septic - drug therapy Shock, Septic - microbiology |
| title | Neutralization of staphylococcal enterotoxin B by an aptamer antagonist |
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