The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance
Summary Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and...
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Veröffentlicht in: | Environmental microbiology 2021-12, Vol.23 (12), p.7723-7740 |
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creator | Majkowska‐Skrobek, Grazyna Markwitz, Pawel Sosnowska, Ewelina Lood, Cédric Lavigne, Rob Drulis‐Kawa, Zuzanna |
description | Summary
Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and microbiological assessment, we show that the receptor‐modification resistance to capsule‐targeting phages involves either escape mutation(s) in the capsule biosynthesis cluster or qualitative changes in exopolysaccharides, converting clones to mucoid variants. These variants introduce cross‐resistance to phages specific to the same receptor yet sensitize to phages utilizing alternative ones. The loss/modification of capsule, the main Klebsiella pneumoniae virulence factor, did not dramatically impact population fitness, nor the ability to protect bacteria against the innate immune response. Nevertheless, the introduction of phage drives bacteria to expel multidrug resistance clusters, as observed by the large deletion in K. pneumoniae 77 plasmid containing blaCTX‐M, ant(3″), sul2, folA, mph(E)/mph(G) genes. The emerging bacterial resistance to viral infection steers evolution towards desired population attributes and highlights the synergistic potential for combined antibiotic‐phage therapy against K. pneumoniae. |
doi_str_mv | 10.1111/1462-2920.15476 |
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Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and microbiological assessment, we show that the receptor‐modification resistance to capsule‐targeting phages involves either escape mutation(s) in the capsule biosynthesis cluster or qualitative changes in exopolysaccharides, converting clones to mucoid variants. These variants introduce cross‐resistance to phages specific to the same receptor yet sensitize to phages utilizing alternative ones. The loss/modification of capsule, the main Klebsiella pneumoniae virulence factor, did not dramatically impact population fitness, nor the ability to protect bacteria against the innate immune response. Nevertheless, the introduction of phage drives bacteria to expel multidrug resistance clusters, as observed by the large deletion in K. pneumoniae 77 plasmid containing blaCTX‐M, ant(3″), sul2, folA, mph(E)/mph(G) genes. The emerging bacterial resistance to viral infection steers evolution towards desired population attributes and highlights the synergistic potential for combined antibiotic‐phage therapy against K. pneumoniae.</description><identifier>ISSN: 1462-2912</identifier><identifier>EISSN: 1462-2920</identifier><identifier>DOI: 10.1111/1462-2920.15476</identifier><identifier>PMID: 33754440</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Antiinfectives and antibacterials ; Bacteria ; Bacteriophages - genetics ; Biosynthesis ; Clones ; Defence mechanisms ; Drug Resistance, Multiple ; Evolutionary genetics ; Exopolysaccharides ; Genes ; Humans ; Immune response ; Immunity ; Innate immunity ; Klebsiella ; Klebsiella Infections - microbiology ; Klebsiella pneumoniae ; Klebsiella pneumoniae - genetics ; Multidrug resistance ; Mutation ; Phage Therapy ; Phages ; Plasmids ; Receptors ; Virulence ; Virulence factors</subject><ispartof>Environmental microbiology, 2021-12, Vol.23 (12), p.7723-7740</ispartof><rights>2021 Society for Applied Microbiology and John Wiley & Sons Ltd.</rights><rights>2021 Society for Applied Microbiology and John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3716-49e119e7a3b61158053a85c48077b506224d50a438660cb2ff5778f910baf5303</citedby><cites>FETCH-LOGICAL-c3716-49e119e7a3b61158053a85c48077b506224d50a438660cb2ff5778f910baf5303</cites><orcidid>0000-0001-7826-3378 ; 0000-0002-4733-4660</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1462-2920.15476$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1462-2920.15476$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33754440$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Majkowska‐Skrobek, Grazyna</creatorcontrib><creatorcontrib>Markwitz, Pawel</creatorcontrib><creatorcontrib>Sosnowska, Ewelina</creatorcontrib><creatorcontrib>Lood, Cédric</creatorcontrib><creatorcontrib>Lavigne, Rob</creatorcontrib><creatorcontrib>Drulis‐Kawa, Zuzanna</creatorcontrib><title>The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance</title><title>Environmental microbiology</title><addtitle>Environ Microbiol</addtitle><description>Summary
Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and microbiological assessment, we show that the receptor‐modification resistance to capsule‐targeting phages involves either escape mutation(s) in the capsule biosynthesis cluster or qualitative changes in exopolysaccharides, converting clones to mucoid variants. These variants introduce cross‐resistance to phages specific to the same receptor yet sensitize to phages utilizing alternative ones. The loss/modification of capsule, the main Klebsiella pneumoniae virulence factor, did not dramatically impact population fitness, nor the ability to protect bacteria against the innate immune response. Nevertheless, the introduction of phage drives bacteria to expel multidrug resistance clusters, as observed by the large deletion in K. pneumoniae 77 plasmid containing blaCTX‐M, ant(3″), sul2, folA, mph(E)/mph(G) genes. The emerging bacterial resistance to viral infection steers evolution towards desired population attributes and highlights the synergistic potential for combined antibiotic‐phage therapy against K. pneumoniae.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Antiinfectives and antibacterials</subject><subject>Bacteria</subject><subject>Bacteriophages - genetics</subject><subject>Biosynthesis</subject><subject>Clones</subject><subject>Defence mechanisms</subject><subject>Drug Resistance, Multiple</subject><subject>Evolutionary genetics</subject><subject>Exopolysaccharides</subject><subject>Genes</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity</subject><subject>Innate immunity</subject><subject>Klebsiella</subject><subject>Klebsiella Infections - microbiology</subject><subject>Klebsiella pneumoniae</subject><subject>Klebsiella pneumoniae - genetics</subject><subject>Multidrug resistance</subject><subject>Mutation</subject><subject>Phage Therapy</subject><subject>Phages</subject><subject>Plasmids</subject><subject>Receptors</subject><subject>Virulence</subject><subject>Virulence factors</subject><issn>1462-2912</issn><issn>1462-2920</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9uFSEUh4mxsbW6dmdI3HRzLf-ZWZqm1cY23dQ1YWYOLQ0DV5ipqSsfwIXP6JPI3NvehZuygQPf-QL8EHpHyUdaxzEViq1Yy2ophVYv0MFu5-VuTdk-el3KHSFUc01eoX3OtRRCkAP0-_oWMNynME8-RZsf8JTtAH9__UnOFewjXt_am6XOUHyZbJzw1wBd8RCCxesI85iit1USJ-sD7nMqpeKbNlwgFj_5n3axYxsHHOoxTg6Pc5j8kOcb_CTu4Q3aczYUePs4H6JvZ6fXJ19WF1efz08-Xax6rqlaiRYobUFb3ilKZUMkt43sRUO07iRRjIlBEit4oxTpO-ac1LpxLSWddZITfoiOtt51Tt9nKJMZfemXB0VIczFMEsFFq4Ss6If_0Ls051hvZ5hilCpBaFup4y21eX0GZ9bZj_U3DSVmCcosUZglFrMJqna8f_TO3QjDjn9KpgJyC_zwAR6e85nTy_Ot-B88raEZ</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Majkowska‐Skrobek, Grazyna</creator><creator>Markwitz, Pawel</creator><creator>Sosnowska, Ewelina</creator><creator>Lood, Cédric</creator><creator>Lavigne, Rob</creator><creator>Drulis‐Kawa, Zuzanna</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</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>7QH</scope><scope>7QL</scope><scope>7ST</scope><scope>7T7</scope><scope>7TN</scope><scope>7U9</scope><scope>7UA</scope><scope>8FD</scope><scope>C1K</scope><scope>F1W</scope><scope>FR3</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>M7N</scope><scope>P64</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7826-3378</orcidid><orcidid>https://orcid.org/0000-0002-4733-4660</orcidid></search><sort><creationdate>202112</creationdate><title>The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance</title><author>Majkowska‐Skrobek, Grazyna ; Markwitz, Pawel ; Sosnowska, Ewelina ; Lood, Cédric ; Lavigne, Rob ; Drulis‐Kawa, Zuzanna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3716-49e119e7a3b61158053a85c48077b506224d50a438660cb2ff5778f910baf5303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>Antiinfectives and antibacterials</topic><topic>Bacteria</topic><topic>Bacteriophages - genetics</topic><topic>Biosynthesis</topic><topic>Clones</topic><topic>Defence mechanisms</topic><topic>Drug Resistance, Multiple</topic><topic>Evolutionary genetics</topic><topic>Exopolysaccharides</topic><topic>Genes</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunity</topic><topic>Innate immunity</topic><topic>Klebsiella</topic><topic>Klebsiella Infections - microbiology</topic><topic>Klebsiella pneumoniae</topic><topic>Klebsiella pneumoniae - genetics</topic><topic>Multidrug resistance</topic><topic>Mutation</topic><topic>Phage Therapy</topic><topic>Phages</topic><topic>Plasmids</topic><topic>Receptors</topic><topic>Virulence</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Majkowska‐Skrobek, Grazyna</creatorcontrib><creatorcontrib>Markwitz, Pawel</creatorcontrib><creatorcontrib>Sosnowska, Ewelina</creatorcontrib><creatorcontrib>Lood, Cédric</creatorcontrib><creatorcontrib>Lavigne, Rob</creatorcontrib><creatorcontrib>Drulis‐Kawa, Zuzanna</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oceanic Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Majkowska‐Skrobek, Grazyna</au><au>Markwitz, Pawel</au><au>Sosnowska, Ewelina</au><au>Lood, Cédric</au><au>Lavigne, Rob</au><au>Drulis‐Kawa, Zuzanna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance</atitle><jtitle>Environmental microbiology</jtitle><addtitle>Environ Microbiol</addtitle><date>2021-12</date><risdate>2021</risdate><volume>23</volume><issue>12</issue><spage>7723</spage><epage>7740</epage><pages>7723-7740</pages><issn>1462-2912</issn><eissn>1462-2920</eissn><abstract>Summary
Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and microbiological assessment, we show that the receptor‐modification resistance to capsule‐targeting phages involves either escape mutation(s) in the capsule biosynthesis cluster or qualitative changes in exopolysaccharides, converting clones to mucoid variants. These variants introduce cross‐resistance to phages specific to the same receptor yet sensitize to phages utilizing alternative ones. The loss/modification of capsule, the main Klebsiella pneumoniae virulence factor, did not dramatically impact population fitness, nor the ability to protect bacteria against the innate immune response. Nevertheless, the introduction of phage drives bacteria to expel multidrug resistance clusters, as observed by the large deletion in K. pneumoniae 77 plasmid containing blaCTX‐M, ant(3″), sul2, folA, mph(E)/mph(G) genes. The emerging bacterial resistance to viral infection steers evolution towards desired population attributes and highlights the synergistic potential for combined antibiotic‐phage therapy against K. pneumoniae.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>33754440</pmid><doi>10.1111/1462-2920.15476</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0001-7826-3378</orcidid><orcidid>https://orcid.org/0000-0002-4733-4660</orcidid></addata></record> |
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subjects | Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Antibiotics Antiinfectives and antibacterials Bacteria Bacteriophages - genetics Biosynthesis Clones Defence mechanisms Drug Resistance, Multiple Evolutionary genetics Exopolysaccharides Genes Humans Immune response Immunity Innate immunity Klebsiella Klebsiella Infections - microbiology Klebsiella pneumoniae Klebsiella pneumoniae - genetics Multidrug resistance Mutation Phage Therapy Phages Plasmids Receptors Virulence Virulence factors |
title | The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance |
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