Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae
Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify no...
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| creator | Guo, Yingyi Liu, Ningjing Lin, Zhiwei Ba, Xiaoliang Zhuo, Chuyue Li, Feifeng Wang, Jiong Li, Yitan Yao, Likang Liu, Baomo Xiao, Shunian Jiang, Ying Zhuo, Chao |
| description | Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated bla
KPC
genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, bla
KPC
expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased bla
KPC
expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp. |
| doi_str_mv | 10.1080/22221751.2021.1984182 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_34551677</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_b81a4a29f017452eb0621d75543751e5</doaj_id><sourcerecordid>2575834300</sourcerecordid><originalsourceid>FETCH-LOGICAL-c534t-eeb4a6478394add959eddab06fafd759633033829c942d8088bd026a4685245a3</originalsourceid><addsrcrecordid>eNp9UUtv1DAQjhCIVqU_AZQjlyx-Js4FASseVRfBAc7WxJ4srpI42E6r8utx2G3VXpiDbc18D2u-onhJyYYSRd6wXLSRdMMIoxvaKkEVe1Kcrv1qHTx98D4pzmO8IrkaUgsqnhcnXEhJ66Y5LcavS4Lk_BRLN5WzD_ncwfihNH5KwXVLwjL50mCf4I-zbsQKrl0HJsFYBowuJpgMruTL79tqDt4uxk378nLALjocBijnCZfRTw7wRfGshyHi-fE-K35--vhj-6Xafft8sX2_q4zkIlWInYBaNIq3AqxtZYvWQkfqHnrbyLbmnHCuWGtawawiSnWWsBpErSQTEvhZcXHQtR6u9BzcCOFWe3D6X8OHvYaQnBlQd4qCANb2hDZCMswujGYTKXjeHcqs9fagNS_diNZg3gsMj0QfTyb3S-_9tVayblpaZ4HXR4Hgfy8Ykx5dNOtmJvRL1Ew2UnHBCclQeYCa4GMM2N_bUKLX5PVd8npNXh-Tz7xXD_94z7rLOQPeHQBu6n0Y4caHweoEt4MPfcgJuqj5_z3-AhInveo</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2575834300</pqid></control><display><type>article</type><title>Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae</title><source>Taylor & Francis Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Guo, Yingyi ; Liu, Ningjing ; Lin, Zhiwei ; Ba, Xiaoliang ; Zhuo, Chuyue ; Li, Feifeng ; Wang, Jiong ; Li, Yitan ; Yao, Likang ; Liu, Baomo ; Xiao, Shunian ; Jiang, Ying ; Zhuo, Chao</creator><creatorcontrib>Guo, Yingyi ; Liu, Ningjing ; Lin, Zhiwei ; Ba, Xiaoliang ; Zhuo, Chuyue ; Li, Feifeng ; Wang, Jiong ; Li, Yitan ; Yao, Likang ; Liu, Baomo ; Xiao, Shunian ; Jiang, Ying ; Zhuo, Chao</creatorcontrib><description>Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated bla
KPC
genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, bla
KPC
expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased bla
KPC
expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.</description><identifier>ISSN: 2222-1751</identifier><identifier>EISSN: 2222-1751</identifier><identifier>DOI: 10.1080/22221751.2021.1984182</identifier><identifier>PMID: 34551677</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Anti-Bacterial Agents - pharmacology ; Azabicyclo Compounds - pharmacology ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; beta-Lactamases - genetics ; beta-Lactamases - metabolism ; Carbapenem-Resistant Enterobacteriaceae - drug effects ; Carbapenem-Resistant Enterobacteriaceae - genetics ; Carbapenem-Resistant Enterobacteriaceae - metabolism ; Ceftazidime - pharmacology ; Ceftazidime-avibactam ; Drug Combinations ; Drug Resistance, Bacterial ; expression level of bla ; expression level of blaKPC ; Humans ; Klebsiella Infections - microbiology ; KPC ; LamB ; Original ; PBP3 ; Porins - genetics ; Porins - metabolism</subject><ispartof>Emerging microbes & infections, 2021-01, Vol.10 (1), p.2042-2051</ispartof><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd 2021</rights><rights>2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd 2021 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-eeb4a6478394add959eddab06fafd759633033829c942d8088bd026a4685245a3</citedby><cites>FETCH-LOGICAL-c534t-eeb4a6478394add959eddab06fafd759633033829c942d8088bd026a4685245a3</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/PMC8567916/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567916/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27481,27903,27904,53769,53771,59119,59120</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34551677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Yingyi</creatorcontrib><creatorcontrib>Liu, Ningjing</creatorcontrib><creatorcontrib>Lin, Zhiwei</creatorcontrib><creatorcontrib>Ba, Xiaoliang</creatorcontrib><creatorcontrib>Zhuo, Chuyue</creatorcontrib><creatorcontrib>Li, Feifeng</creatorcontrib><creatorcontrib>Wang, Jiong</creatorcontrib><creatorcontrib>Li, Yitan</creatorcontrib><creatorcontrib>Yao, Likang</creatorcontrib><creatorcontrib>Liu, Baomo</creatorcontrib><creatorcontrib>Xiao, Shunian</creatorcontrib><creatorcontrib>Jiang, Ying</creatorcontrib><creatorcontrib>Zhuo, Chao</creatorcontrib><title>Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae</title><title>Emerging microbes & infections</title><addtitle>Emerg Microbes Infect</addtitle><description>Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated bla
KPC
genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, bla
KPC
expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased bla
KPC
expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Azabicyclo Compounds - pharmacology</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>beta-Lactamases - genetics</subject><subject>beta-Lactamases - metabolism</subject><subject>Carbapenem-Resistant Enterobacteriaceae - drug effects</subject><subject>Carbapenem-Resistant Enterobacteriaceae - genetics</subject><subject>Carbapenem-Resistant Enterobacteriaceae - metabolism</subject><subject>Ceftazidime - pharmacology</subject><subject>Ceftazidime-avibactam</subject><subject>Drug Combinations</subject><subject>Drug Resistance, Bacterial</subject><subject>expression level of bla</subject><subject>expression level of blaKPC</subject><subject>Humans</subject><subject>Klebsiella Infections - microbiology</subject><subject>KPC</subject><subject>LamB</subject><subject>Original</subject><subject>PBP3</subject><subject>Porins - genetics</subject><subject>Porins - metabolism</subject><issn>2222-1751</issn><issn>2222-1751</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9UUtv1DAQjhCIVqU_AZQjlyx-Js4FASseVRfBAc7WxJ4srpI42E6r8utx2G3VXpiDbc18D2u-onhJyYYSRd6wXLSRdMMIoxvaKkEVe1Kcrv1qHTx98D4pzmO8IrkaUgsqnhcnXEhJ66Y5LcavS4Lk_BRLN5WzD_ncwfihNH5KwXVLwjL50mCf4I-zbsQKrl0HJsFYBowuJpgMruTL79tqDt4uxk378nLALjocBijnCZfRTw7wRfGshyHi-fE-K35--vhj-6Xafft8sX2_q4zkIlWInYBaNIq3AqxtZYvWQkfqHnrbyLbmnHCuWGtawawiSnWWsBpErSQTEvhZcXHQtR6u9BzcCOFWe3D6X8OHvYaQnBlQd4qCANb2hDZCMswujGYTKXjeHcqs9fagNS_diNZg3gsMj0QfTyb3S-_9tVayblpaZ4HXR4Hgfy8Ykx5dNOtmJvRL1Ew2UnHBCclQeYCa4GMM2N_bUKLX5PVd8npNXh-Tz7xXD_94z7rLOQPeHQBu6n0Y4caHweoEt4MPfcgJuqj5_z3-AhInveo</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Guo, Yingyi</creator><creator>Liu, Ningjing</creator><creator>Lin, Zhiwei</creator><creator>Ba, Xiaoliang</creator><creator>Zhuo, Chuyue</creator><creator>Li, Feifeng</creator><creator>Wang, Jiong</creator><creator>Li, Yitan</creator><creator>Yao, Likang</creator><creator>Liu, Baomo</creator><creator>Xiao, Shunian</creator><creator>Jiang, Ying</creator><creator>Zhuo, Chao</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>0YH</scope><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><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20210101</creationdate><title>Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae</title><author>Guo, Yingyi ; Liu, Ningjing ; Lin, Zhiwei ; Ba, Xiaoliang ; Zhuo, Chuyue ; Li, Feifeng ; Wang, Jiong ; Li, Yitan ; Yao, Likang ; Liu, Baomo ; Xiao, Shunian ; Jiang, Ying ; Zhuo, Chao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-eeb4a6478394add959eddab06fafd759633033829c942d8088bd026a4685245a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Azabicyclo Compounds - pharmacology</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>beta-Lactamases - genetics</topic><topic>beta-Lactamases - metabolism</topic><topic>Carbapenem-Resistant Enterobacteriaceae - drug effects</topic><topic>Carbapenem-Resistant Enterobacteriaceae - genetics</topic><topic>Carbapenem-Resistant Enterobacteriaceae - metabolism</topic><topic>Ceftazidime - pharmacology</topic><topic>Ceftazidime-avibactam</topic><topic>Drug Combinations</topic><topic>Drug Resistance, Bacterial</topic><topic>expression level of bla</topic><topic>expression level of blaKPC</topic><topic>Humans</topic><topic>Klebsiella Infections - microbiology</topic><topic>KPC</topic><topic>LamB</topic><topic>Original</topic><topic>PBP3</topic><topic>Porins - genetics</topic><topic>Porins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Yingyi</creatorcontrib><creatorcontrib>Liu, Ningjing</creatorcontrib><creatorcontrib>Lin, Zhiwei</creatorcontrib><creatorcontrib>Ba, Xiaoliang</creatorcontrib><creatorcontrib>Zhuo, Chuyue</creatorcontrib><creatorcontrib>Li, Feifeng</creatorcontrib><creatorcontrib>Wang, Jiong</creatorcontrib><creatorcontrib>Li, Yitan</creatorcontrib><creatorcontrib>Yao, Likang</creatorcontrib><creatorcontrib>Liu, Baomo</creatorcontrib><creatorcontrib>Xiao, Shunian</creatorcontrib><creatorcontrib>Jiang, Ying</creatorcontrib><creatorcontrib>Zhuo, Chao</creatorcontrib><collection>Taylor & Francis Open Access</collection><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><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Emerging microbes & infections</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Yingyi</au><au>Liu, Ningjing</au><au>Lin, Zhiwei</au><au>Ba, Xiaoliang</au><au>Zhuo, Chuyue</au><au>Li, Feifeng</au><au>Wang, Jiong</au><au>Li, Yitan</au><au>Yao, Likang</au><au>Liu, Baomo</au><au>Xiao, Shunian</au><au>Jiang, Ying</au><au>Zhuo, Chao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae</atitle><jtitle>Emerging microbes & infections</jtitle><addtitle>Emerg Microbes Infect</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>10</volume><issue>1</issue><spage>2042</spage><epage>2051</epage><pages>2042-2051</pages><issn>2222-1751</issn><eissn>2222-1751</eissn><abstract>Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated bla
KPC
genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, bla
KPC
expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased bla
KPC
expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>34551677</pmid><doi>10.1080/22221751.2021.1984182</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Taylor & Francis Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Anti-Bacterial Agents - pharmacology Azabicyclo Compounds - pharmacology Bacterial Proteins - genetics Bacterial Proteins - metabolism beta-Lactamases - genetics beta-Lactamases - metabolism Carbapenem-Resistant Enterobacteriaceae - drug effects Carbapenem-Resistant Enterobacteriaceae - genetics Carbapenem-Resistant Enterobacteriaceae - metabolism Ceftazidime - pharmacology Ceftazidime-avibactam Drug Combinations Drug Resistance, Bacterial expression level of bla expression level of blaKPC Humans Klebsiella Infections - microbiology KPC LamB Original PBP3 Porins - genetics Porins - metabolism |
| title | Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae |
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