A Novel Sialylation Site on Neisseria gonorrhoeae Lipooligosaccharide Links Heptose II Lactose Expression with Pathogenicity
Sialylation of lacto- -neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both Hep...
Gespeichert in:
Veröffentlicht in: | Infection and immunity 2018-08, Vol.86 (8) |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 8 |
container_start_page | |
container_title | Infection and immunity |
container_volume | 86 |
creator | Ram, Sanjay Gulati, Sunita Lewis, Lisa A Chakraborti, Srinjoy Zheng, Bo DeOliveira, Rosane B Reed, George W Cox, Andrew D Li, Jianjun St Michael, Frank Stupak, Jacek Su, Xiao-Hong Saha, Sudeshna Landig, Corinna S Varki, Ajit Rice, Peter A |
description | Sialylation of lacto-
-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for monoclonal antibody (MAb) 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-
-acetylneuraminic acid (CMP-Neu5Ac)-containing medium enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOSs of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and an MS11 mutant with lactose only from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6 linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. Strain 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with MAb 2C7; MAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. MAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose
Our findings reinforce the candidacy of the 2C7 epitope as a vaccine antigen and MAb 2C7 as an immunotherapeutic antibody. |
doi_str_mv | 10.1128/IAI.00285-18 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6056883</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2047250448</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-8ff22e83ac9654ea1d25c4438bb74c172e42d626a35288eb173147cb5dd36c003</originalsourceid><addsrcrecordid>eNpVUctu2zAQJIoGtZPm1nPBYw9VwqdEXQoYRh4CjCRAmjNBUWuLrSyqJO3GQD4-ch5Ge5rZ3cHsYgehL5ScUcrUeTWrzghhSmZUfUBTSkqVScnYRzQlhJZZKfNigo5j_DWWQgj1CU1YqYRgvJiipxm-8Vvo8L0z3a4zyfl-5AnwiDfgYoTgDF753ofQejCAF27wvnMrH421rQmu2ff63xFfw5B8BFxVeGHsC714HALEuHf961KL70xq_Qp6Z13afUZHS9NFOH3DE_RwefFzfp0tbq-q-WyRWa5EytRyyRgobmyZSwGGNkxaIbiq60JYWjAQrMlZbrhkSkFNC05FYWvZNDy3hPAT9OPVd9jUa2gs9CmYTg_BrU3YaW-c_n_Su1av_FbnROZK8dHg25tB8H82EJNeu2ih60wPfhM1I6JgkozPHaXfX6U2-BgDLA9rKNH7wPQYmH4JTNO9_Ou_px3E7wnxZxw2k5U</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2047250448</pqid></control><display><type>article</type><title>A Novel Sialylation Site on Neisseria gonorrhoeae Lipooligosaccharide Links Heptose II Lactose Expression with Pathogenicity</title><source>American Society for Microbiology</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Ram, Sanjay ; Gulati, Sunita ; Lewis, Lisa A ; Chakraborti, Srinjoy ; Zheng, Bo ; DeOliveira, Rosane B ; Reed, George W ; Cox, Andrew D ; Li, Jianjun ; St Michael, Frank ; Stupak, Jacek ; Su, Xiao-Hong ; Saha, Sudeshna ; Landig, Corinna S ; Varki, Ajit ; Rice, Peter A</creator><contributor>Payne, Shelley M.</contributor><creatorcontrib>Ram, Sanjay ; Gulati, Sunita ; Lewis, Lisa A ; Chakraborti, Srinjoy ; Zheng, Bo ; DeOliveira, Rosane B ; Reed, George W ; Cox, Andrew D ; Li, Jianjun ; St Michael, Frank ; Stupak, Jacek ; Su, Xiao-Hong ; Saha, Sudeshna ; Landig, Corinna S ; Varki, Ajit ; Rice, Peter A ; Payne, Shelley M.</creatorcontrib><description>Sialylation of lacto-
-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for monoclonal antibody (MAb) 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-
-acetylneuraminic acid (CMP-Neu5Ac)-containing medium enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOSs of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and an MS11 mutant with lactose only from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6 linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. Strain 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with MAb 2C7; MAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. MAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose
Our findings reinforce the candidacy of the 2C7 epitope as a vaccine antigen and MAb 2C7 as an immunotherapeutic antibody.</description><identifier>ISSN: 0019-9567</identifier><identifier>EISSN: 1098-5522</identifier><identifier>DOI: 10.1128/IAI.00285-18</identifier><identifier>PMID: 29844237</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Molecular Pathogenesis</subject><ispartof>Infection and immunity, 2018-08, Vol.86 (8)</ispartof><rights>Copyright © 2018 American Society for Microbiology.</rights><rights>Copyright © 2018 American Society for Microbiology. 2018 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-8ff22e83ac9654ea1d25c4438bb74c172e42d626a35288eb173147cb5dd36c003</citedby><cites>FETCH-LOGICAL-c384t-8ff22e83ac9654ea1d25c4438bb74c172e42d626a35288eb173147cb5dd36c003</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/PMC6056883/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056883/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,3174,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29844237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Payne, Shelley M.</contributor><creatorcontrib>Ram, Sanjay</creatorcontrib><creatorcontrib>Gulati, Sunita</creatorcontrib><creatorcontrib>Lewis, Lisa A</creatorcontrib><creatorcontrib>Chakraborti, Srinjoy</creatorcontrib><creatorcontrib>Zheng, Bo</creatorcontrib><creatorcontrib>DeOliveira, Rosane B</creatorcontrib><creatorcontrib>Reed, George W</creatorcontrib><creatorcontrib>Cox, Andrew D</creatorcontrib><creatorcontrib>Li, Jianjun</creatorcontrib><creatorcontrib>St Michael, Frank</creatorcontrib><creatorcontrib>Stupak, Jacek</creatorcontrib><creatorcontrib>Su, Xiao-Hong</creatorcontrib><creatorcontrib>Saha, Sudeshna</creatorcontrib><creatorcontrib>Landig, Corinna S</creatorcontrib><creatorcontrib>Varki, Ajit</creatorcontrib><creatorcontrib>Rice, Peter A</creatorcontrib><title>A Novel Sialylation Site on Neisseria gonorrhoeae Lipooligosaccharide Links Heptose II Lactose Expression with Pathogenicity</title><title>Infection and immunity</title><addtitle>Infect Immun</addtitle><description>Sialylation of lacto-
-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for monoclonal antibody (MAb) 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-
-acetylneuraminic acid (CMP-Neu5Ac)-containing medium enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOSs of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and an MS11 mutant with lactose only from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6 linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. Strain 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with MAb 2C7; MAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. MAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose
Our findings reinforce the candidacy of the 2C7 epitope as a vaccine antigen and MAb 2C7 as an immunotherapeutic antibody.</description><subject>Molecular Pathogenesis</subject><issn>0019-9567</issn><issn>1098-5522</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpVUctu2zAQJIoGtZPm1nPBYw9VwqdEXQoYRh4CjCRAmjNBUWuLrSyqJO3GQD4-ch5Ge5rZ3cHsYgehL5ScUcrUeTWrzghhSmZUfUBTSkqVScnYRzQlhJZZKfNigo5j_DWWQgj1CU1YqYRgvJiipxm-8Vvo8L0z3a4zyfl-5AnwiDfgYoTgDF753ofQejCAF27wvnMrH421rQmu2ff63xFfw5B8BFxVeGHsC714HALEuHf961KL70xq_Qp6Z13afUZHS9NFOH3DE_RwefFzfp0tbq-q-WyRWa5EytRyyRgobmyZSwGGNkxaIbiq60JYWjAQrMlZbrhkSkFNC05FYWvZNDy3hPAT9OPVd9jUa2gs9CmYTg_BrU3YaW-c_n_Su1av_FbnROZK8dHg25tB8H82EJNeu2ih60wPfhM1I6JgkozPHaXfX6U2-BgDLA9rKNH7wPQYmH4JTNO9_Ou_px3E7wnxZxw2k5U</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Ram, Sanjay</creator><creator>Gulati, Sunita</creator><creator>Lewis, Lisa A</creator><creator>Chakraborti, Srinjoy</creator><creator>Zheng, Bo</creator><creator>DeOliveira, Rosane B</creator><creator>Reed, George W</creator><creator>Cox, Andrew D</creator><creator>Li, Jianjun</creator><creator>St Michael, Frank</creator><creator>Stupak, Jacek</creator><creator>Su, Xiao-Hong</creator><creator>Saha, Sudeshna</creator><creator>Landig, Corinna S</creator><creator>Varki, Ajit</creator><creator>Rice, Peter A</creator><general>American Society for Microbiology</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180801</creationdate><title>A Novel Sialylation Site on Neisseria gonorrhoeae Lipooligosaccharide Links Heptose II Lactose Expression with Pathogenicity</title><author>Ram, Sanjay ; Gulati, Sunita ; Lewis, Lisa A ; Chakraborti, Srinjoy ; Zheng, Bo ; DeOliveira, Rosane B ; Reed, George W ; Cox, Andrew D ; Li, Jianjun ; St Michael, Frank ; Stupak, Jacek ; Su, Xiao-Hong ; Saha, Sudeshna ; Landig, Corinna S ; Varki, Ajit ; Rice, Peter A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-8ff22e83ac9654ea1d25c4438bb74c172e42d626a35288eb173147cb5dd36c003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Molecular Pathogenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ram, Sanjay</creatorcontrib><creatorcontrib>Gulati, Sunita</creatorcontrib><creatorcontrib>Lewis, Lisa A</creatorcontrib><creatorcontrib>Chakraborti, Srinjoy</creatorcontrib><creatorcontrib>Zheng, Bo</creatorcontrib><creatorcontrib>DeOliveira, Rosane B</creatorcontrib><creatorcontrib>Reed, George W</creatorcontrib><creatorcontrib>Cox, Andrew D</creatorcontrib><creatorcontrib>Li, Jianjun</creatorcontrib><creatorcontrib>St Michael, Frank</creatorcontrib><creatorcontrib>Stupak, Jacek</creatorcontrib><creatorcontrib>Su, Xiao-Hong</creatorcontrib><creatorcontrib>Saha, Sudeshna</creatorcontrib><creatorcontrib>Landig, Corinna S</creatorcontrib><creatorcontrib>Varki, Ajit</creatorcontrib><creatorcontrib>Rice, Peter A</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Infection and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ram, Sanjay</au><au>Gulati, Sunita</au><au>Lewis, Lisa A</au><au>Chakraborti, Srinjoy</au><au>Zheng, Bo</au><au>DeOliveira, Rosane B</au><au>Reed, George W</au><au>Cox, Andrew D</au><au>Li, Jianjun</au><au>St Michael, Frank</au><au>Stupak, Jacek</au><au>Su, Xiao-Hong</au><au>Saha, Sudeshna</au><au>Landig, Corinna S</au><au>Varki, Ajit</au><au>Rice, Peter A</au><au>Payne, Shelley M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Sialylation Site on Neisseria gonorrhoeae Lipooligosaccharide Links Heptose II Lactose Expression with Pathogenicity</atitle><jtitle>Infection and immunity</jtitle><addtitle>Infect Immun</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>86</volume><issue>8</issue><issn>0019-9567</issn><eissn>1098-5522</eissn><abstract>Sialylation of lacto-
-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for monoclonal antibody (MAb) 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-
-acetylneuraminic acid (CMP-Neu5Ac)-containing medium enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOSs of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and an MS11 mutant with lactose only from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6 linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. Strain 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with MAb 2C7; MAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. MAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose
Our findings reinforce the candidacy of the 2C7 epitope as a vaccine antigen and MAb 2C7 as an immunotherapeutic antibody.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>29844237</pmid><doi>10.1128/IAI.00285-18</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0019-9567 |
ispartof | Infection and immunity, 2018-08, Vol.86 (8) |
issn | 0019-9567 1098-5522 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6056883 |
source | American Society for Microbiology; EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | Molecular Pathogenesis |
title | A Novel Sialylation Site on Neisseria gonorrhoeae Lipooligosaccharide Links Heptose II Lactose Expression with Pathogenicity |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T16%3A11%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Novel%20Sialylation%20Site%20on%20Neisseria%20gonorrhoeae%20Lipooligosaccharide%20Links%20Heptose%20II%20Lactose%20Expression%20with%20Pathogenicity&rft.jtitle=Infection%20and%20immunity&rft.au=Ram,%20Sanjay&rft.date=2018-08-01&rft.volume=86&rft.issue=8&rft.issn=0019-9567&rft.eissn=1098-5522&rft_id=info:doi/10.1128/IAI.00285-18&rft_dat=%3Cproquest_pubme%3E2047250448%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2047250448&rft_id=info:pmid/29844237&rfr_iscdi=true |