Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus
Methicillin-resistant (MRSA) strains carry either a - or a -mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the string...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy 2018-06, Vol.62 (6), p.e00206-18 |
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| creator | Pardos de la Gandara, Maria Borges, Vitor Chung, Marilyn Milheiriço, Catarina Gomes, João Paulo de Lencastre, Herminia Tomasz, Alexander |
| description | Methicillin-resistant
(MRSA) strains carry either a
- or a
-mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the
-carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes (
,
,
,
,
, and
), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA. |
| doi_str_mv | 10.1128/AAC.00206-18 |
| format | Article |
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(MRSA) strains carry either a
- or a
-mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the
-carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes (
,
,
,
,
, and
), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.00206-18</identifier><identifier>PMID: 29555636</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Anti-Bacterial Agents ; Anti-Bacterial Agents - pharmacology ; Bacterial Proteins ; Bacterial Proteins - genetics ; Bacteriology ; Biochemistry, Molecular Biology ; Denmark ; Genomics ; Guanine ; Guanine - metabolism ; Humans ; Life Sciences ; Mechanisms of Resistance ; Methicillin Resistance ; Methicillin Resistance - genetics ; Methicillin-Resistant Staphylococcus aureus ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Methicillin-Resistant Staphylococcus aureus - genetics ; Methicillin-Resistant Staphylococcus aureus - isolation & purification ; Microbial Sensitivity Tests ; Microbiology and Parasitology ; Molecular biology ; Oxacillin ; Oxacillin - pharmacology ; Penicillin-Binding Proteins ; Penicillin-Binding Proteins - genetics ; United Kingdom ; Whole Genome Sequencing</subject><ispartof>Antimicrobial agents and chemotherapy, 2018-06, Vol.62 (6), p.e00206-18</ispartof><rights>Copyright © 2018 American Society for Microbiology.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</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-a550t-58bf22aa62ff3d6431b9346bef95b357e1d0e978d6cd98ceff007300fcbfa55d3</citedby><cites>FETCH-LOGICAL-a550t-58bf22aa62ff3d6431b9346bef95b357e1d0e978d6cd98ceff007300fcbfa55d3</cites><orcidid>0000-0002-3273-6392 ; 0000-0002-2825-8850 ; 0000-0003-1520-1983 ; 0000-0001-6816-8932</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971597/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971597/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29555636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-02861189$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Pardos de la Gandara, Maria</creatorcontrib><creatorcontrib>Borges, Vitor</creatorcontrib><creatorcontrib>Chung, Marilyn</creatorcontrib><creatorcontrib>Milheiriço, Catarina</creatorcontrib><creatorcontrib>Gomes, João Paulo</creatorcontrib><creatorcontrib>de Lencastre, Herminia</creatorcontrib><creatorcontrib>Tomasz, Alexander</creatorcontrib><title>Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Methicillin-resistant
(MRSA) strains carry either a
- or a
-mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the
-carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes (
,
,
,
,
, and
), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.</description><subject>Anti-Bacterial Agents</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Bacterial Proteins</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacteriology</subject><subject>Biochemistry, Molecular Biology</subject><subject>Denmark</subject><subject>Genomics</subject><subject>Guanine</subject><subject>Guanine - metabolism</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Mechanisms of Resistance</subject><subject>Methicillin Resistance</subject><subject>Methicillin Resistance - genetics</subject><subject>Methicillin-Resistant Staphylococcus aureus</subject><subject>Methicillin-Resistant Staphylococcus aureus - drug effects</subject><subject>Methicillin-Resistant Staphylococcus aureus - genetics</subject><subject>Methicillin-Resistant Staphylococcus aureus - isolation & purification</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology and Parasitology</subject><subject>Molecular biology</subject><subject>Oxacillin</subject><subject>Oxacillin - pharmacology</subject><subject>Penicillin-Binding Proteins</subject><subject>Penicillin-Binding Proteins - genetics</subject><subject>United Kingdom</subject><subject>Whole Genome Sequencing</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV1rFDEUhoModlu981rmUqGpJzObTHIjLKt2hZWCH9chkznppMzHmmQW---NTltU8CKEw_vkCclLyAsGF4yV8s1ms70AKEFQJh-RFQMlqeBKPCYrACHoWsL6hJzGeAN55gqekpNScc5FJVbEXeKIydviHSYMgx_NmGIxuWLnrzu6xyP2xdUPY33f-7H4jNHHZEaLRZ4-Yer8ktD7JBVfkjl0t_1kJ2vnWJg54ByfkSfO9BGf3-1n5NuH91-3O7q_uvy43eyp4RwS5bJxZWmMKJ2rWrGuWKOqtWjQKd5UvEbWAqpatsK2Slp0DqCuAJxtXDa01Rl5u3gPczNga3FMwfT6EPxgwq2ejNd_J6Pv9PV01FzVLK8soIug--fYbrPXBxMTzkFDKQVjUh1Z5l_dXRim7zPGpAcfLfa9GXGaoy6BcVnVUENGzxfUhinGgO7Bz0D_qlLnKvXvKjWTGX-94CYOpb6Z5jDmn_sf-_LPZz-I73uufgJK0aiV</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Pardos de la Gandara, Maria</creator><creator>Borges, Vitor</creator><creator>Chung, Marilyn</creator><creator>Milheiriço, Catarina</creator><creator>Gomes, João Paulo</creator><creator>de Lencastre, Herminia</creator><creator>Tomasz, Alexander</creator><general>American Society for Microbiology</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><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3273-6392</orcidid><orcidid>https://orcid.org/0000-0002-2825-8850</orcidid><orcidid>https://orcid.org/0000-0003-1520-1983</orcidid><orcidid>https://orcid.org/0000-0001-6816-8932</orcidid></search><sort><creationdate>20180601</creationdate><title>Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus</title><author>Pardos de la Gandara, Maria ; Borges, Vitor ; Chung, Marilyn ; Milheiriço, Catarina ; Gomes, João Paulo ; de Lencastre, Herminia ; Tomasz, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a550t-58bf22aa62ff3d6431b9346bef95b357e1d0e978d6cd98ceff007300fcbfa55d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Anti-Bacterial Agents</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Bacterial Proteins</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacteriology</topic><topic>Biochemistry, Molecular Biology</topic><topic>Denmark</topic><topic>Genomics</topic><topic>Guanine</topic><topic>Guanine - metabolism</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Mechanisms of Resistance</topic><topic>Methicillin Resistance</topic><topic>Methicillin Resistance - genetics</topic><topic>Methicillin-Resistant Staphylococcus aureus</topic><topic>Methicillin-Resistant Staphylococcus aureus - drug effects</topic><topic>Methicillin-Resistant Staphylococcus aureus - genetics</topic><topic>Methicillin-Resistant Staphylococcus aureus - isolation & purification</topic><topic>Microbial Sensitivity Tests</topic><topic>Microbiology and Parasitology</topic><topic>Molecular biology</topic><topic>Oxacillin</topic><topic>Oxacillin - pharmacology</topic><topic>Penicillin-Binding Proteins</topic><topic>Penicillin-Binding Proteins - genetics</topic><topic>United Kingdom</topic><topic>Whole Genome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pardos de la Gandara, Maria</creatorcontrib><creatorcontrib>Borges, Vitor</creatorcontrib><creatorcontrib>Chung, Marilyn</creatorcontrib><creatorcontrib>Milheiriço, Catarina</creatorcontrib><creatorcontrib>Gomes, João Paulo</creatorcontrib><creatorcontrib>de Lencastre, Herminia</creatorcontrib><creatorcontrib>Tomasz, Alexander</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><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pardos de la Gandara, Maria</au><au>Borges, Vitor</au><au>Chung, Marilyn</au><au>Milheiriço, Catarina</au><au>Gomes, João Paulo</au><au>de Lencastre, Herminia</au><au>Tomasz, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>62</volume><issue>6</issue><spage>e00206</spage><epage>18</epage><pages>e00206-18</pages><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Methicillin-resistant
(MRSA) strains carry either a
- or a
-mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the
-carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes (
,
,
,
,
, and
), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>29555636</pmid><doi>10.1128/AAC.00206-18</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3273-6392</orcidid><orcidid>https://orcid.org/0000-0002-2825-8850</orcidid><orcidid>https://orcid.org/0000-0003-1520-1983</orcidid><orcidid>https://orcid.org/0000-0001-6816-8932</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Antimicrobial agents and chemotherapy, 2018-06, Vol.62 (6), p.e00206-18 |
| issn | 0066-4804 1098-6596 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5971597 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Anti-Bacterial Agents Anti-Bacterial Agents - pharmacology Bacterial Proteins Bacterial Proteins - genetics Bacteriology Biochemistry, Molecular Biology Denmark Genomics Guanine Guanine - metabolism Humans Life Sciences Mechanisms of Resistance Methicillin Resistance Methicillin Resistance - genetics Methicillin-Resistant Staphylococcus aureus Methicillin-Resistant Staphylococcus aureus - drug effects Methicillin-Resistant Staphylococcus aureus - genetics Methicillin-Resistant Staphylococcus aureus - isolation & purification Microbial Sensitivity Tests Microbiology and Parasitology Molecular biology Oxacillin Oxacillin - pharmacology Penicillin-Binding Proteins Penicillin-Binding Proteins - genetics United Kingdom Whole Genome Sequencing |
| title | Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus |
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