Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae
Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited. To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-d...
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Veröffentlicht in: | Journal of antimicrobial chemotherapy 2017-11, Vol.72 (11), p.3035-3042 |
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container_title | Journal of antimicrobial chemotherapy |
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creator | Leung, Lisa M Cooper, Vaughn S Rasko, David A Guo, Qinglan Pacey, Marissa P McElheny, Christi L Mettus, Roberta T Yoon, Sung Hwan Goodlett, David R Ernst, Robert K Doi, Yohei |
description | Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.
To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.
The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.
All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2 mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.
The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings. |
doi_str_mv | 10.1093/jac/dkx234 |
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To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.
The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.
All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2 mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.
The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkx234</identifier><identifier>PMID: 28961916</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Aged ; Amino Sugars - pharmacology ; Anti-Bacterial Agents - pharmacology ; Bacterial Proteins - genetics ; beta-Lactamases - biosynthesis ; Chromosomes, Bacterial ; Colistin - pharmacology ; Drug Resistance, Bacterial - genetics ; Female ; Humans ; Klebsiella Infections - microbiology ; Klebsiella pneumoniae - chemistry ; Klebsiella pneumoniae - drug effects ; Klebsiella pneumoniae - enzymology ; Klebsiella pneumoniae - genetics ; Lipid A - chemistry ; Lipid A - metabolism ; Lipopolysaccharides - chemistry ; Male ; Membrane Proteins - genetics ; Microbial Sensitivity Tests ; Middle Aged ; Mutagenesis, Insertional ; Original Research</subject><ispartof>Journal of antimicrobial chemotherapy, 2017-11, Vol.72 (11), p.3035-3042</ispartof><rights>The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><rights>The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-20fb10ef5bd4650cfdeb90be9dfeeabbd6a4e0135d6b0b177ee05eda87985123</citedby><cites>FETCH-LOGICAL-c378t-20fb10ef5bd4650cfdeb90be9dfeeabbd6a4e0135d6b0b177ee05eda87985123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28961916$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leung, Lisa M</creatorcontrib><creatorcontrib>Cooper, Vaughn S</creatorcontrib><creatorcontrib>Rasko, David A</creatorcontrib><creatorcontrib>Guo, Qinglan</creatorcontrib><creatorcontrib>Pacey, Marissa P</creatorcontrib><creatorcontrib>McElheny, Christi L</creatorcontrib><creatorcontrib>Mettus, Roberta T</creatorcontrib><creatorcontrib>Yoon, Sung Hwan</creatorcontrib><creatorcontrib>Goodlett, David R</creatorcontrib><creatorcontrib>Ernst, Robert K</creatorcontrib><creatorcontrib>Doi, Yohei</creatorcontrib><title>Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.
To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.
The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.
All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2 mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.
The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.</description><subject>Adult</subject><subject>Aged</subject><subject>Amino Sugars - pharmacology</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Bacterial Proteins - genetics</subject><subject>beta-Lactamases - biosynthesis</subject><subject>Chromosomes, Bacterial</subject><subject>Colistin - pharmacology</subject><subject>Drug Resistance, Bacterial - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Klebsiella Infections - microbiology</subject><subject>Klebsiella pneumoniae - chemistry</subject><subject>Klebsiella pneumoniae - drug effects</subject><subject>Klebsiella pneumoniae - enzymology</subject><subject>Klebsiella pneumoniae - genetics</subject><subject>Lipid A - chemistry</subject><subject>Lipid A - metabolism</subject><subject>Lipopolysaccharides - chemistry</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Microbial Sensitivity Tests</subject><subject>Middle Aged</subject><subject>Mutagenesis, Insertional</subject><subject>Original Research</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkFtLw0AQhRdRbK2--AMkz2LsbDaby4sgxRstWGhffAp7mdStyW7IJqL_3ki16NMMzJkzZz5CzilcU8jZdCvUVL99RCw-IGMaJxBGkNNDMgYGPExjzkbkxPstACQ8yY7JKMryhOY0GZOXVdf2qutbUQW106Y0SnTG2cCVwWK5CowNlKuM74wNW_RDI2x3FcyXs7Bpne6VsZtgXqH0BqtKBI3FvnbWCDwlR6WoPJ791AlZ39-tZ4_h4vnhaXa7CBVLs26IWkoKWHKp44SDKjXKHCTmukQUUupExAiUcZ1IkDRNEYGjFlmaZ5xGbEJudrZNL2vUCm03_FI0ralF-1k4YYr_E2tei417L3iWQ0rZYHC5M1Ct877Fcr9LofjmWwx8ix3fQXzx99pe-guUfQEdqXs5</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Leung, Lisa M</creator><creator>Cooper, Vaughn S</creator><creator>Rasko, David A</creator><creator>Guo, Qinglan</creator><creator>Pacey, Marissa P</creator><creator>McElheny, Christi L</creator><creator>Mettus, Roberta T</creator><creator>Yoon, Sung Hwan</creator><creator>Goodlett, David R</creator><creator>Ernst, Robert K</creator><creator>Doi, Yohei</creator><general>Oxford University Press</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>5PM</scope></search><sort><creationdate>20171101</creationdate><title>Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae</title><author>Leung, Lisa M ; Cooper, Vaughn S ; Rasko, David A ; Guo, Qinglan ; Pacey, Marissa P ; McElheny, Christi L ; Mettus, Roberta T ; Yoon, Sung Hwan ; Goodlett, David R ; Ernst, Robert K ; Doi, Yohei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-20fb10ef5bd4650cfdeb90be9dfeeabbd6a4e0135d6b0b177ee05eda87985123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Amino Sugars - pharmacology</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Bacterial Proteins - genetics</topic><topic>beta-Lactamases - biosynthesis</topic><topic>Chromosomes, Bacterial</topic><topic>Colistin - pharmacology</topic><topic>Drug Resistance, Bacterial - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Klebsiella Infections - microbiology</topic><topic>Klebsiella pneumoniae - chemistry</topic><topic>Klebsiella pneumoniae - drug effects</topic><topic>Klebsiella pneumoniae - enzymology</topic><topic>Klebsiella pneumoniae - genetics</topic><topic>Lipid A - chemistry</topic><topic>Lipid A - metabolism</topic><topic>Lipopolysaccharides - chemistry</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Microbial Sensitivity Tests</topic><topic>Middle Aged</topic><topic>Mutagenesis, Insertional</topic><topic>Original Research</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leung, Lisa M</creatorcontrib><creatorcontrib>Cooper, Vaughn S</creatorcontrib><creatorcontrib>Rasko, David A</creatorcontrib><creatorcontrib>Guo, Qinglan</creatorcontrib><creatorcontrib>Pacey, Marissa P</creatorcontrib><creatorcontrib>McElheny, Christi L</creatorcontrib><creatorcontrib>Mettus, Roberta T</creatorcontrib><creatorcontrib>Yoon, Sung Hwan</creatorcontrib><creatorcontrib>Goodlett, David R</creatorcontrib><creatorcontrib>Ernst, Robert K</creatorcontrib><creatorcontrib>Doi, Yohei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leung, Lisa M</au><au>Cooper, Vaughn S</au><au>Rasko, David A</au><au>Guo, Qinglan</au><au>Pacey, Marissa P</au><au>McElheny, Christi L</au><au>Mettus, Roberta T</au><au>Yoon, Sung Hwan</au><au>Goodlett, David R</au><au>Ernst, Robert K</au><au>Doi, Yohei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>72</volume><issue>11</issue><spage>3035</spage><epage>3042</epage><pages>3035-3042</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.
To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.
The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.
All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2 mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.
The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>28961916</pmid><doi>10.1093/jac/dkx234</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Amino Sugars - pharmacology Anti-Bacterial Agents - pharmacology Bacterial Proteins - genetics beta-Lactamases - biosynthesis Chromosomes, Bacterial Colistin - pharmacology Drug Resistance, Bacterial - genetics Female Humans Klebsiella Infections - microbiology Klebsiella pneumoniae - chemistry Klebsiella pneumoniae - drug effects Klebsiella pneumoniae - enzymology Klebsiella pneumoniae - genetics Lipid A - chemistry Lipid A - metabolism Lipopolysaccharides - chemistry Male Membrane Proteins - genetics Microbial Sensitivity Tests Middle Aged Mutagenesis, Insertional Original Research |
title | Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae |
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