Impact of agr dysfunction on virulence profiles and infections associated with a novel methicillin-resistant Staphylococcus aureus (MRSA) variant of the lineage ST1-SCCmec IV
A novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro. Bacterial biofilm has been considered a major virulence factor in central venous catheter-associated BSI. The...
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| Veröffentlicht in: | BMC microbiology 2013-04, Vol.13 (1), p.93-93, Article 93 |
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| creator | Ferreira, Fabienne Antunes Souza, Raquel Rodrigues de Sousa Moraes, Bruno de Amorim Ferreira, Ana Maria Américo, Marco Antônio Fracalanzza, Sérgio Eduardo Longo Dos Santos Silva Couceiro, José Nelson Sá Figueiredo, Agnes Marie |
| description | A novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro. Bacterial biofilm has been considered a major virulence factor in central venous catheter-associated BSI. The mechanisms involved in biofilm formation/accumulation are multifactorial and complex. Studies have suggested that biofilm production was affected in vitro and vivo for agr-null mutants of S. aureus.
The impact of naturally occurring inhibition of agr signaling on virulence profiles and infections associated with the ST1 variant was investigated. agr dysfunction was detected in a significant percentage (13%) of the isolates with concomitant increase in biofilm accumulation in vitro and in vivo, and enhanced ability to adhere to and invade airway cells. The biofilm formed by these ST1 isolates was ica-independent and proteinaceous in nature. In fact, the improved colonization properties were paralleled by an increased expression of the biofilm-associated genes fnbA, spa and sasG. The transcription of sarA, a positive regulator of agr, was two-times reduced for the agr-dysfunctional MRSA. Remarkably, the agr inhibition was genetically stable. Indeed, agr-dysfunctional isolates succeed to colonize and cause both acute and chronic infections in hospitalized patients, and also to effectively accumulate biofilm in a mouse subcutaneous catheter implant model.
The ability of agr-dysfunctional isolates to cause infections in humans and to form biofilm in the animal model suggests that therapeutic approaches based on agr-inactivation strategies are unlikely to be effective in controlling human-device infections caused by ST1 isolates. The increased biofilm accumulation associated with the acquisition of multiple antimicrobial resistant traits might have influenced (at least in part) the expansion of this USA400 related clone in our hospitals. |
| doi_str_mv | 10.1186/1471-2180-13-93 |
| format | Article |
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The impact of naturally occurring inhibition of agr signaling on virulence profiles and infections associated with the ST1 variant was investigated. agr dysfunction was detected in a significant percentage (13%) of the isolates with concomitant increase in biofilm accumulation in vitro and in vivo, and enhanced ability to adhere to and invade airway cells. The biofilm formed by these ST1 isolates was ica-independent and proteinaceous in nature. In fact, the improved colonization properties were paralleled by an increased expression of the biofilm-associated genes fnbA, spa and sasG. The transcription of sarA, a positive regulator of agr, was two-times reduced for the agr-dysfunctional MRSA. Remarkably, the agr inhibition was genetically stable. Indeed, agr-dysfunctional isolates succeed to colonize and cause both acute and chronic infections in hospitalized patients, and also to effectively accumulate biofilm in a mouse subcutaneous catheter implant model.
The ability of agr-dysfunctional isolates to cause infections in humans and to form biofilm in the animal model suggests that therapeutic approaches based on agr-inactivation strategies are unlikely to be effective in controlling human-device infections caused by ST1 isolates. The increased biofilm accumulation associated with the acquisition of multiple antimicrobial resistant traits might have influenced (at least in part) the expansion of this USA400 related clone in our hospitals.</description><identifier>ISSN: 1471-2180</identifier><identifier>EISSN: 1471-2180</identifier><identifier>DOI: 10.1186/1471-2180-13-93</identifier><identifier>PMID: 23622558</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Animals ; Bacterial Adhesion ; Bacterial Proteins ; Bacteriology ; Biofilms ; Biofilms - growth & development ; Brazil ; Care and treatment ; Catheter-Related Infections - microbiology ; Disease Models, Animal ; Drug resistance in microorganisms ; Endocytosis ; Genetic aspects ; Genotype ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus - classification ; Methicillin-Resistant Staphylococcus aureus - isolation & purification ; Methicillin-Resistant Staphylococcus aureus - pathogenicity ; Methicillin-Resistant Staphylococcus aureus - physiology ; Mice ; Mice, Inbred BALB C ; Microbiology ; Molecular Typing ; Proteins ; Staphylococcal Infections - microbiology ; Staphylococcus aureus ; Staphylococcus aureus infections ; Staphylococcus infections ; Trans-Activators - deficiency ; Virulence ; Virulence (Microbiology)</subject><ispartof>BMC microbiology, 2013-04, Vol.13 (1), p.93-93, Article 93</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Ferreira et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Ferreira et al.; licensee BioMed Central Ltd. 2013 Ferreira et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b614t-7422b15ba21b4214ccc280665d2b90c59217fa2613b7bf64159eddf372bd448a3</citedby><cites>FETCH-LOGICAL-b614t-7422b15ba21b4214ccc280665d2b90c59217fa2613b7bf64159eddf372bd448a3</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/PMC3652751/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652751/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23622558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferreira, Fabienne Antunes</creatorcontrib><creatorcontrib>Souza, Raquel Rodrigues</creatorcontrib><creatorcontrib>de Sousa Moraes, Bruno</creatorcontrib><creatorcontrib>de Amorim Ferreira, Ana Maria</creatorcontrib><creatorcontrib>Américo, Marco Antônio</creatorcontrib><creatorcontrib>Fracalanzza, Sérgio Eduardo Longo</creatorcontrib><creatorcontrib>Dos Santos Silva Couceiro, José Nelson</creatorcontrib><creatorcontrib>Sá Figueiredo, Agnes Marie</creatorcontrib><title>Impact of agr dysfunction on virulence profiles and infections associated with a novel methicillin-resistant Staphylococcus aureus (MRSA) variant of the lineage ST1-SCCmec IV</title><title>BMC microbiology</title><addtitle>BMC Microbiol</addtitle><description>A novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro. Bacterial biofilm has been considered a major virulence factor in central venous catheter-associated BSI. The mechanisms involved in biofilm formation/accumulation are multifactorial and complex. Studies have suggested that biofilm production was affected in vitro and vivo for agr-null mutants of S. aureus.
The impact of naturally occurring inhibition of agr signaling on virulence profiles and infections associated with the ST1 variant was investigated. agr dysfunction was detected in a significant percentage (13%) of the isolates with concomitant increase in biofilm accumulation in vitro and in vivo, and enhanced ability to adhere to and invade airway cells. The biofilm formed by these ST1 isolates was ica-independent and proteinaceous in nature. In fact, the improved colonization properties were paralleled by an increased expression of the biofilm-associated genes fnbA, spa and sasG. The transcription of sarA, a positive regulator of agr, was two-times reduced for the agr-dysfunctional MRSA. Remarkably, the agr inhibition was genetically stable. Indeed, agr-dysfunctional isolates succeed to colonize and cause both acute and chronic infections in hospitalized patients, and also to effectively accumulate biofilm in a mouse subcutaneous catheter implant model.
The ability of agr-dysfunctional isolates to cause infections in humans and to form biofilm in the animal model suggests that therapeutic approaches based on agr-inactivation strategies are unlikely to be effective in controlling human-device infections caused by ST1 isolates. The increased biofilm accumulation associated with the acquisition of multiple antimicrobial resistant traits might have influenced (at least in part) the expansion of this USA400 related clone in our hospitals.</description><subject>Analysis</subject><subject>Animals</subject><subject>Bacterial Adhesion</subject><subject>Bacterial Proteins</subject><subject>Bacteriology</subject><subject>Biofilms</subject><subject>Biofilms - growth & development</subject><subject>Brazil</subject><subject>Care and treatment</subject><subject>Catheter-Related Infections - microbiology</subject><subject>Disease Models, Animal</subject><subject>Drug resistance in microorganisms</subject><subject>Endocytosis</subject><subject>Genetic aspects</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Methicillin-Resistant Staphylococcus aureus - classification</subject><subject>Methicillin-Resistant Staphylococcus aureus - isolation & purification</subject><subject>Methicillin-Resistant Staphylococcus aureus - pathogenicity</subject><subject>Methicillin-Resistant Staphylococcus aureus - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Molecular Typing</subject><subject>Proteins</subject><subject>Staphylococcal Infections - microbiology</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus infections</subject><subject>Staphylococcus infections</subject><subject>Trans-Activators - deficiency</subject><subject>Virulence</subject><subject>Virulence (Microbiology)</subject><issn>1471-2180</issn><issn>1471-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkk1v1DAQhiMEoqVw5oYscWkPaePPJBeksuJjpSKkbuFqOc5k11Vib21nYf8UvxGHlqWLioRsafzxvK9GM5NlL3FxinElzjArcU5wVeSY5jV9lB3uXh7fOx9kz0K4LgpcVrR8mh0QKgjhvDrMfsyHtdIRuQ6ppUftNnSj1dE4i9LeGD_2YDWgtXed6SEgZVtkbAe_mHQNwWmjIrTom4krpJB1G-jRAHFltOl7Y3MPwYSobESLqNarbe-003pM4tFDCsefLhfnJ2ijvJmglEpcAUpKUEtAiyucL2azATSaf32ePelUH-DFXTzKvrx_dzX7mF98_jCfnV_kjcAs5iUjpMG8UQQ3jGCmtSZVIQRvSVMXmtcEl50iAtOmbDrBMK-hbTtakqZlrFL0KHtz67semwFaDTZ61cu1N4PyW-mUkfs_1qzk0m0kFZyUHCeDt7cGjXH_MNj_0W6QU7_k1C-JqaxpMjm-y8K7mxFClIMJGvpeWXBjSBQXNS2qiv0PikVR1own9PVf6LUbvU3lnChaYEaq-g-1VD3I1HGX0tSTqTznlHFR1GLyOn2ASquFwWhnYRqafcHJniAxEb7HpRpDkPPF5T57dstq70Lw0O3Kh1OF0vg_ULBX99u243_PO_0JxiIADg</recordid><startdate>20130427</startdate><enddate>20130427</enddate><creator>Ferreira, Fabienne Antunes</creator><creator>Souza, Raquel Rodrigues</creator><creator>de Sousa Moraes, Bruno</creator><creator>de Amorim Ferreira, Ana Maria</creator><creator>Américo, Marco Antônio</creator><creator>Fracalanzza, Sérgio Eduardo Longo</creator><creator>Dos Santos Silva Couceiro, José Nelson</creator><creator>Sá Figueiredo, Agnes Marie</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130427</creationdate><title>Impact of agr dysfunction on virulence profiles and infections associated with a novel methicillin-resistant Staphylococcus aureus (MRSA) variant of the lineage ST1-SCCmec IV</title><author>Ferreira, Fabienne Antunes ; Souza, Raquel Rodrigues ; de Sousa Moraes, Bruno ; de Amorim Ferreira, Ana Maria ; Américo, Marco Antônio ; Fracalanzza, Sérgio Eduardo Longo ; Dos Santos Silva Couceiro, José Nelson ; Sá Figueiredo, Agnes Marie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b614t-7422b15ba21b4214ccc280665d2b90c59217fa2613b7bf64159eddf372bd448a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Bacterial Adhesion</topic><topic>Bacterial Proteins</topic><topic>Bacteriology</topic><topic>Biofilms</topic><topic>Biofilms - growth & development</topic><topic>Brazil</topic><topic>Care and treatment</topic><topic>Catheter-Related Infections - microbiology</topic><topic>Disease Models, Animal</topic><topic>Drug resistance in microorganisms</topic><topic>Endocytosis</topic><topic>Genetic aspects</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Methicillin-Resistant Staphylococcus aureus - classification</topic><topic>Methicillin-Resistant Staphylococcus aureus - isolation & purification</topic><topic>Methicillin-Resistant Staphylococcus aureus - pathogenicity</topic><topic>Methicillin-Resistant Staphylococcus aureus - physiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Molecular Typing</topic><topic>Proteins</topic><topic>Staphylococcal Infections - microbiology</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus infections</topic><topic>Staphylococcus infections</topic><topic>Trans-Activators - deficiency</topic><topic>Virulence</topic><topic>Virulence (Microbiology)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferreira, Fabienne Antunes</creatorcontrib><creatorcontrib>Souza, Raquel Rodrigues</creatorcontrib><creatorcontrib>de Sousa Moraes, Bruno</creatorcontrib><creatorcontrib>de Amorim Ferreira, Ana Maria</creatorcontrib><creatorcontrib>Américo, Marco Antônio</creatorcontrib><creatorcontrib>Fracalanzza, Sérgio Eduardo Longo</creatorcontrib><creatorcontrib>Dos Santos Silva Couceiro, José Nelson</creatorcontrib><creatorcontrib>Sá Figueiredo, Agnes Marie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferreira, Fabienne Antunes</au><au>Souza, Raquel Rodrigues</au><au>de Sousa Moraes, Bruno</au><au>de Amorim Ferreira, Ana Maria</au><au>Américo, Marco Antônio</au><au>Fracalanzza, Sérgio Eduardo Longo</au><au>Dos Santos Silva Couceiro, José Nelson</au><au>Sá Figueiredo, Agnes Marie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of agr dysfunction on virulence profiles and infections associated with a novel methicillin-resistant Staphylococcus aureus (MRSA) variant of the lineage ST1-SCCmec IV</atitle><jtitle>BMC microbiology</jtitle><addtitle>BMC Microbiol</addtitle><date>2013-04-27</date><risdate>2013</risdate><volume>13</volume><issue>1</issue><spage>93</spage><epage>93</epage><pages>93-93</pages><artnum>93</artnum><issn>1471-2180</issn><eissn>1471-2180</eissn><abstract>A novel variant of the ST1-SCCmecIV methicillin-resistant Staphylococcus aureus (MRSA) lineage, mostly associated with nosocomial bloodstream infections (BSI), has emerged in Rio de Janeiro. Bacterial biofilm has been considered a major virulence factor in central venous catheter-associated BSI. The mechanisms involved in biofilm formation/accumulation are multifactorial and complex. Studies have suggested that biofilm production was affected in vitro and vivo for agr-null mutants of S. aureus.
The impact of naturally occurring inhibition of agr signaling on virulence profiles and infections associated with the ST1 variant was investigated. agr dysfunction was detected in a significant percentage (13%) of the isolates with concomitant increase in biofilm accumulation in vitro and in vivo, and enhanced ability to adhere to and invade airway cells. The biofilm formed by these ST1 isolates was ica-independent and proteinaceous in nature. In fact, the improved colonization properties were paralleled by an increased expression of the biofilm-associated genes fnbA, spa and sasG. The transcription of sarA, a positive regulator of agr, was two-times reduced for the agr-dysfunctional MRSA. Remarkably, the agr inhibition was genetically stable. Indeed, agr-dysfunctional isolates succeed to colonize and cause both acute and chronic infections in hospitalized patients, and also to effectively accumulate biofilm in a mouse subcutaneous catheter implant model.
The ability of agr-dysfunctional isolates to cause infections in humans and to form biofilm in the animal model suggests that therapeutic approaches based on agr-inactivation strategies are unlikely to be effective in controlling human-device infections caused by ST1 isolates. The increased biofilm accumulation associated with the acquisition of multiple antimicrobial resistant traits might have influenced (at least in part) the expansion of this USA400 related clone in our hospitals.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23622558</pmid><doi>10.1186/1471-2180-13-93</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | BMC microbiology, 2013-04, Vol.13 (1), p.93-93, Article 93 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Springer Nature OA Free Journals; Springer Nature - Complete Springer Journals; PubMed Central |
| subjects | Analysis Animals Bacterial Adhesion Bacterial Proteins Bacteriology Biofilms Biofilms - growth & development Brazil Care and treatment Catheter-Related Infections - microbiology Disease Models, Animal Drug resistance in microorganisms Endocytosis Genetic aspects Genotype Humans Male Methicillin-Resistant Staphylococcus aureus - classification Methicillin-Resistant Staphylococcus aureus - isolation & purification Methicillin-Resistant Staphylococcus aureus - pathogenicity Methicillin-Resistant Staphylococcus aureus - physiology Mice Mice, Inbred BALB C Microbiology Molecular Typing Proteins Staphylococcal Infections - microbiology Staphylococcus aureus Staphylococcus aureus infections Staphylococcus infections Trans-Activators - deficiency Virulence Virulence (Microbiology) |
| title | Impact of agr dysfunction on virulence profiles and infections associated with a novel methicillin-resistant Staphylococcus aureus (MRSA) variant of the lineage ST1-SCCmec IV |
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