A novel resistance gene, lnu(H), conferring resistance to lincosamides in Riemerella anatipestifer CH-2
•First report of lnu(H), a novel lincosamide nucleotidylyltransferase gene.•lnu(H) confers high-level lincosamide resistance in Riemerella anatipestifer CH-2.•Lnu(H) catalysed adenylylation of lincosamides as demonstrated by mass spectrometry.•lnu(H) is widely distributed and transferrable among R....
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| Veröffentlicht in: | International journal of antimicrobial agents 2018-01, Vol.51 (1), p.136-139 |
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| creator | Luo, Hong-Yan Liu, Ma-Feng Wang, Ming-Shu Zhao, Xin-Xin Jia, Ren-Yong Chen, Shun Sun, Kun-Feng Yang, Qiao Wu, Ying Chen, Xiao-Yue Biville, Francis Zou, Yuan-Feng Jing, Bo Cheng, An-Chun Zhu, De-Kang |
| description | •First report of lnu(H), a novel lincosamide nucleotidylyltransferase gene.•lnu(H) confers high-level lincosamide resistance in Riemerella anatipestifer CH-2.•Lnu(H) catalysed adenylylation of lincosamides as demonstrated by mass spectrometry.•lnu(H) is widely distributed and transferrable among R. anatipestifer isolates.
The Gram-negative bacterium Riemerella anatipestifer CH-2 is resistant to lincosamides, having a lincomycin (LCM) minimum inhibitory concentration (MIC) of 128 µg/mL. The G148_1775 gene of R. anatipestifer CH-2, designated lnu(H), encodes a 260-amino acid protein with ≤41% identity to other reported lincosamide nucleotidylyltransferases. Escherichia coli RosettaTM (DE3) containing the pBAD24-lnu(H) plasmid showed four- and two-fold increases in the MICs of LCM and clindamycin (CLI), respectively. A kinetic assay of the purified Lnu(H) enzyme for LCM and CLI showed that the protein could inactive lincosamides. Mass spectrometry analysis demonstrated that the Lnu(H) enzyme catalysed adenylylation of lincosamides. In addition, an lnu(H) gene deletion strain exhibited 512- and 32-fold decreases in LCM and CLI MICs, respectively. The wild-type level of lincosamide resistance could be restored by complementation with a shuttle plasmid carrying the lnu(H) gene. The transformant R. anatipestifer ATCC 11845 [lnu(H)] acquired by natural transformation also exhibited high-level lincosamide resistance. Moreover, among 175 R. anatipestifer field isolates, 56 (32.0%) were positive for the lnu(H) gene by PCR. In conclusion, Lnu(H) is a novel lincosamide nucleotidylyltransferase that inactivates LCM and CLI by nucleotidylylation, thus conferring high-level lincosamide resistance to R. anatipestifer CH-2. |
| doi_str_mv | 10.1016/j.ijantimicag.2017.08.022 |
| format | Article |
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The Gram-negative bacterium Riemerella anatipestifer CH-2 is resistant to lincosamides, having a lincomycin (LCM) minimum inhibitory concentration (MIC) of 128 µg/mL. The G148_1775 gene of R. anatipestifer CH-2, designated lnu(H), encodes a 260-amino acid protein with ≤41% identity to other reported lincosamide nucleotidylyltransferases. Escherichia coli RosettaTM (DE3) containing the pBAD24-lnu(H) plasmid showed four- and two-fold increases in the MICs of LCM and clindamycin (CLI), respectively. A kinetic assay of the purified Lnu(H) enzyme for LCM and CLI showed that the protein could inactive lincosamides. Mass spectrometry analysis demonstrated that the Lnu(H) enzyme catalysed adenylylation of lincosamides. In addition, an lnu(H) gene deletion strain exhibited 512- and 32-fold decreases in LCM and CLI MICs, respectively. The wild-type level of lincosamide resistance could be restored by complementation with a shuttle plasmid carrying the lnu(H) gene. The transformant R. anatipestifer ATCC 11845 [lnu(H)] acquired by natural transformation also exhibited high-level lincosamide resistance. Moreover, among 175 R. anatipestifer field isolates, 56 (32.0%) were positive for the lnu(H) gene by PCR. In conclusion, Lnu(H) is a novel lincosamide nucleotidylyltransferase that inactivates LCM and CLI by nucleotidylylation, thus conferring high-level lincosamide resistance to R. anatipestifer CH-2.</description><identifier>ISSN: 0924-8579</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2017.08.022</identifier><identifier>PMID: 28843817</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Anti-Bacterial Agents - pharmacology ; Bacterial Proteins - genetics ; China ; Clindamycin - pharmacology ; Drug Resistance, Bacterial - genetics ; Ducks - microbiology ; Flavobacteriaceae Infections - microbiology ; Flavobacteriaceae Infections - veterinary ; Lincosamide resistance ; Lincosamides - pharmacology ; lnu(H) ; Microbial Sensitivity Tests ; Nucleotidyltransferases - genetics ; Nucleotidylyltransferase ; Plasmids - genetics ; Riemerella - drug effects ; Riemerella - genetics ; Riemerella - isolation & purification ; Riemerella anatipestifer</subject><ispartof>International journal of antimicrobial agents, 2018-01, Vol.51 (1), p.136-139</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-fb074d9e6edd8b2c5741cf43a040d5cf19450cc596c8fe4d567e4821685d70333</citedby><cites>FETCH-LOGICAL-c377t-fb074d9e6edd8b2c5741cf43a040d5cf19450cc596c8fe4d567e4821685d70333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S092485791730314X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28843817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Hong-Yan</creatorcontrib><creatorcontrib>Liu, Ma-Feng</creatorcontrib><creatorcontrib>Wang, Ming-Shu</creatorcontrib><creatorcontrib>Zhao, Xin-Xin</creatorcontrib><creatorcontrib>Jia, Ren-Yong</creatorcontrib><creatorcontrib>Chen, Shun</creatorcontrib><creatorcontrib>Sun, Kun-Feng</creatorcontrib><creatorcontrib>Yang, Qiao</creatorcontrib><creatorcontrib>Wu, Ying</creatorcontrib><creatorcontrib>Chen, Xiao-Yue</creatorcontrib><creatorcontrib>Biville, Francis</creatorcontrib><creatorcontrib>Zou, Yuan-Feng</creatorcontrib><creatorcontrib>Jing, Bo</creatorcontrib><creatorcontrib>Cheng, An-Chun</creatorcontrib><creatorcontrib>Zhu, De-Kang</creatorcontrib><title>A novel resistance gene, lnu(H), conferring resistance to lincosamides in Riemerella anatipestifer CH-2</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>•First report of lnu(H), a novel lincosamide nucleotidylyltransferase gene.•lnu(H) confers high-level lincosamide resistance in Riemerella anatipestifer CH-2.•Lnu(H) catalysed adenylylation of lincosamides as demonstrated by mass spectrometry.•lnu(H) is widely distributed and transferrable among R. anatipestifer isolates.
The Gram-negative bacterium Riemerella anatipestifer CH-2 is resistant to lincosamides, having a lincomycin (LCM) minimum inhibitory concentration (MIC) of 128 µg/mL. The G148_1775 gene of R. anatipestifer CH-2, designated lnu(H), encodes a 260-amino acid protein with ≤41% identity to other reported lincosamide nucleotidylyltransferases. Escherichia coli RosettaTM (DE3) containing the pBAD24-lnu(H) plasmid showed four- and two-fold increases in the MICs of LCM and clindamycin (CLI), respectively. A kinetic assay of the purified Lnu(H) enzyme for LCM and CLI showed that the protein could inactive lincosamides. Mass spectrometry analysis demonstrated that the Lnu(H) enzyme catalysed adenylylation of lincosamides. In addition, an lnu(H) gene deletion strain exhibited 512- and 32-fold decreases in LCM and CLI MICs, respectively. The wild-type level of lincosamide resistance could be restored by complementation with a shuttle plasmid carrying the lnu(H) gene. The transformant R. anatipestifer ATCC 11845 [lnu(H)] acquired by natural transformation also exhibited high-level lincosamide resistance. Moreover, among 175 R. anatipestifer field isolates, 56 (32.0%) were positive for the lnu(H) gene by PCR. In conclusion, Lnu(H) is a novel lincosamide nucleotidylyltransferase that inactivates LCM and CLI by nucleotidylylation, thus conferring high-level lincosamide resistance to R. anatipestifer CH-2.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Bacterial Proteins - genetics</subject><subject>China</subject><subject>Clindamycin - pharmacology</subject><subject>Drug Resistance, Bacterial - genetics</subject><subject>Ducks - microbiology</subject><subject>Flavobacteriaceae Infections - microbiology</subject><subject>Flavobacteriaceae Infections - veterinary</subject><subject>Lincosamide resistance</subject><subject>Lincosamides - pharmacology</subject><subject>lnu(H)</subject><subject>Microbial Sensitivity Tests</subject><subject>Nucleotidyltransferases - genetics</subject><subject>Nucleotidylyltransferase</subject><subject>Plasmids - genetics</subject><subject>Riemerella - drug effects</subject><subject>Riemerella - genetics</subject><subject>Riemerella - isolation & purification</subject><subject>Riemerella anatipestifer</subject><issn>0924-8579</issn><issn>1872-7913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1r3DAQhkVpaLZp_kJRbynErj4t6RiWNikECqE9C600Xmax5a3kDeTfx8smJcee5jDPOx8PIV84aznj3bddi7uQZxwxhm0rGDctsy0T4h1ZcWtEYxyX78mKOaEaq407Jx9r3THGtVT6AzkX1ippuVmR7Q3N0yMMtEDFOoccgW4hwzUd8uHq7us1jVPuoRTM27fMPNEBc5xqGDFBpZjpA8IIBYYh0JDDjHuoMy5Rur5rxCdy1oehwuVLvSB_fnz_vXTuf93-XN_cN1EaMzf9hhmVHHSQkt2IqI3isVcyMMWSjj13SrMYteui7UEl3RlQVvDO6mSYlPKCXJ3m7sv097Bc4Ees8XhUhulQPXdSCuGsOaLuhMYy1Vqg9_uCYyhPnjN_9Ox3_o1nf_TsmfWL5yX7-WXNYTNC-pd8FbsA6xMAy7OPCMXXiLCYS1ggzj5N-B9rngFN2JTV</recordid><startdate>201801</startdate><enddate>201801</enddate><creator>Luo, Hong-Yan</creator><creator>Liu, Ma-Feng</creator><creator>Wang, Ming-Shu</creator><creator>Zhao, Xin-Xin</creator><creator>Jia, Ren-Yong</creator><creator>Chen, Shun</creator><creator>Sun, Kun-Feng</creator><creator>Yang, Qiao</creator><creator>Wu, Ying</creator><creator>Chen, Xiao-Yue</creator><creator>Biville, Francis</creator><creator>Zou, Yuan-Feng</creator><creator>Jing, Bo</creator><creator>Cheng, An-Chun</creator><creator>Zhu, De-Kang</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>201801</creationdate><title>A novel resistance gene, lnu(H), conferring resistance to lincosamides in Riemerella anatipestifer CH-2</title><author>Luo, Hong-Yan ; Liu, Ma-Feng ; Wang, Ming-Shu ; Zhao, Xin-Xin ; Jia, Ren-Yong ; Chen, Shun ; Sun, Kun-Feng ; Yang, Qiao ; Wu, Ying ; Chen, Xiao-Yue ; Biville, Francis ; Zou, Yuan-Feng ; Jing, Bo ; Cheng, An-Chun ; Zhu, De-Kang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-fb074d9e6edd8b2c5741cf43a040d5cf19450cc596c8fe4d567e4821685d70333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Bacterial Proteins - genetics</topic><topic>China</topic><topic>Clindamycin - pharmacology</topic><topic>Drug Resistance, Bacterial - genetics</topic><topic>Ducks - microbiology</topic><topic>Flavobacteriaceae Infections - microbiology</topic><topic>Flavobacteriaceae Infections - veterinary</topic><topic>Lincosamide resistance</topic><topic>Lincosamides - pharmacology</topic><topic>lnu(H)</topic><topic>Microbial Sensitivity Tests</topic><topic>Nucleotidyltransferases - genetics</topic><topic>Nucleotidylyltransferase</topic><topic>Plasmids - genetics</topic><topic>Riemerella - drug effects</topic><topic>Riemerella - genetics</topic><topic>Riemerella - isolation & purification</topic><topic>Riemerella anatipestifer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Hong-Yan</creatorcontrib><creatorcontrib>Liu, Ma-Feng</creatorcontrib><creatorcontrib>Wang, Ming-Shu</creatorcontrib><creatorcontrib>Zhao, Xin-Xin</creatorcontrib><creatorcontrib>Jia, Ren-Yong</creatorcontrib><creatorcontrib>Chen, Shun</creatorcontrib><creatorcontrib>Sun, Kun-Feng</creatorcontrib><creatorcontrib>Yang, Qiao</creatorcontrib><creatorcontrib>Wu, Ying</creatorcontrib><creatorcontrib>Chen, Xiao-Yue</creatorcontrib><creatorcontrib>Biville, Francis</creatorcontrib><creatorcontrib>Zou, Yuan-Feng</creatorcontrib><creatorcontrib>Jing, Bo</creatorcontrib><creatorcontrib>Cheng, An-Chun</creatorcontrib><creatorcontrib>Zhu, De-Kang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Hong-Yan</au><au>Liu, Ma-Feng</au><au>Wang, Ming-Shu</au><au>Zhao, Xin-Xin</au><au>Jia, Ren-Yong</au><au>Chen, Shun</au><au>Sun, Kun-Feng</au><au>Yang, Qiao</au><au>Wu, Ying</au><au>Chen, Xiao-Yue</au><au>Biville, Francis</au><au>Zou, Yuan-Feng</au><au>Jing, Bo</au><au>Cheng, An-Chun</au><au>Zhu, De-Kang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel resistance gene, lnu(H), conferring resistance to lincosamides in Riemerella anatipestifer CH-2</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2018-01</date><risdate>2018</risdate><volume>51</volume><issue>1</issue><spage>136</spage><epage>139</epage><pages>136-139</pages><issn>0924-8579</issn><eissn>1872-7913</eissn><abstract>•First report of lnu(H), a novel lincosamide nucleotidylyltransferase gene.•lnu(H) confers high-level lincosamide resistance in Riemerella anatipestifer CH-2.•Lnu(H) catalysed adenylylation of lincosamides as demonstrated by mass spectrometry.•lnu(H) is widely distributed and transferrable among R. anatipestifer isolates.
The Gram-negative bacterium Riemerella anatipestifer CH-2 is resistant to lincosamides, having a lincomycin (LCM) minimum inhibitory concentration (MIC) of 128 µg/mL. The G148_1775 gene of R. anatipestifer CH-2, designated lnu(H), encodes a 260-amino acid protein with ≤41% identity to other reported lincosamide nucleotidylyltransferases. Escherichia coli RosettaTM (DE3) containing the pBAD24-lnu(H) plasmid showed four- and two-fold increases in the MICs of LCM and clindamycin (CLI), respectively. A kinetic assay of the purified Lnu(H) enzyme for LCM and CLI showed that the protein could inactive lincosamides. Mass spectrometry analysis demonstrated that the Lnu(H) enzyme catalysed adenylylation of lincosamides. In addition, an lnu(H) gene deletion strain exhibited 512- and 32-fold decreases in LCM and CLI MICs, respectively. The wild-type level of lincosamide resistance could be restored by complementation with a shuttle plasmid carrying the lnu(H) gene. The transformant R. anatipestifer ATCC 11845 [lnu(H)] acquired by natural transformation also exhibited high-level lincosamide resistance. Moreover, among 175 R. anatipestifer field isolates, 56 (32.0%) were positive for the lnu(H) gene by PCR. In conclusion, Lnu(H) is a novel lincosamide nucleotidylyltransferase that inactivates LCM and CLI by nucleotidylylation, thus conferring high-level lincosamide resistance to R. anatipestifer CH-2.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28843817</pmid><doi>10.1016/j.ijantimicag.2017.08.022</doi><tpages>4</tpages></addata></record> |
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| subjects | Animals Anti-Bacterial Agents - pharmacology Bacterial Proteins - genetics China Clindamycin - pharmacology Drug Resistance, Bacterial - genetics Ducks - microbiology Flavobacteriaceae Infections - microbiology Flavobacteriaceae Infections - veterinary Lincosamide resistance Lincosamides - pharmacology lnu(H) Microbial Sensitivity Tests Nucleotidyltransferases - genetics Nucleotidylyltransferase Plasmids - genetics Riemerella - drug effects Riemerella - genetics Riemerella - isolation & purification Riemerella anatipestifer |
| title | A novel resistance gene, lnu(H), conferring resistance to lincosamides in Riemerella anatipestifer CH-2 |
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