The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus
Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen . Methylhydroquinone (MHQ) caused a thiol-specific oxidative...
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| Veröffentlicht in: | Antioxidants & redox signaling 2019-12, Vol.31 (16), p.1235-1252 |
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| creator | Fritsch, Verena Nadin Loi, Vu Van Busche, Tobias Sommer, Anna Tedin, Karsten Nürnberg, Dennis J Kalinowski, Jörn Bernhardt, Jörg Fulde, Marcus Antelmann, Haike |
| description | Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen
.
Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the
transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The
operon was most strongly upregulated by MHQ and was renamed as
operon based on its homology to the
locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the
operon, which confers quinone and antimicrobial resistance in
. The
operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9-9 bp inverted repeat (MhqR operator) upstream of the
operon and is inactivated by MHQ
, which does not involve a thiol-based mechanism. In phenotypic assays, the
deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the
mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections.
Our results provide a link between quinone and antimicrobial resistance
the MhqR regulon of
.
The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of
under long-term infections. |
| doi_str_mv | 10.1089/ars.2019.7750 |
| format | Article |
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.
Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the
transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The
operon was most strongly upregulated by MHQ and was renamed as
operon based on its homology to the
locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the
operon, which confers quinone and antimicrobial resistance in
. The
operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9-9 bp inverted repeat (MhqR operator) upstream of the
operon and is inactivated by MHQ
, which does not involve a thiol-based mechanism. In phenotypic assays, the
deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the
mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections.
Our results provide a link between quinone and antimicrobial resistance
the MhqR regulon of
.
The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of
under long-term infections.</description><identifier>ISSN: 1523-0864</identifier><identifier>EISSN: 1557-7716</identifier><identifier>DOI: 10.1089/ars.2019.7750</identifier><identifier>PMID: 31310152</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Aldehydes ; Antiinfectives and antibacterials ; Antimicrobial agents ; Antimicrobial resistance ; Ciprofloxacin ; Deletion mutant ; Drug resistance ; Gene deletion ; Gene expression ; Homology ; Hypochlorous acid ; Infections ; Inverted repeat ; Macrophages ; Norfloxacin ; Original Research Communications ; Oxidants ; Oxidizing agents ; Penicillin ; Pyocyanin ; Quinones ; Reactive oxygen species ; Regulatory mechanisms (biology) ; Rifampin ; Staphylococcus aureus ; Staphylococcus infections ; Virulence</subject><ispartof>Antioxidants & redox signaling, 2019-12, Vol.31 (16), p.1235-1252</ispartof><rights>Copyright Mary Ann Liebert, Inc. Dec 1, 2019</rights><rights>Verena Nadin Fritsch . 2019; Published by Mary Ann Liebert, Inc. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-744c0360e7fcc701d3da9566114e7b777bc6130f82d4f2be5d0e4edc11e8acf3</citedby><cites>FETCH-LOGICAL-c376t-744c0360e7fcc701d3da9566114e7b777bc6130f82d4f2be5d0e4edc11e8acf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31310152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fritsch, Verena Nadin</creatorcontrib><creatorcontrib>Loi, Vu Van</creatorcontrib><creatorcontrib>Busche, Tobias</creatorcontrib><creatorcontrib>Sommer, Anna</creatorcontrib><creatorcontrib>Tedin, Karsten</creatorcontrib><creatorcontrib>Nürnberg, Dennis J</creatorcontrib><creatorcontrib>Kalinowski, Jörn</creatorcontrib><creatorcontrib>Bernhardt, Jörg</creatorcontrib><creatorcontrib>Fulde, Marcus</creatorcontrib><creatorcontrib>Antelmann, Haike</creatorcontrib><title>The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus</title><title>Antioxidants & redox signaling</title><addtitle>Antioxid Redox Signal</addtitle><description>Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen
.
Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the
transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The
operon was most strongly upregulated by MHQ and was renamed as
operon based on its homology to the
locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the
operon, which confers quinone and antimicrobial resistance in
. The
operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9-9 bp inverted repeat (MhqR operator) upstream of the
operon and is inactivated by MHQ
, which does not involve a thiol-based mechanism. In phenotypic assays, the
deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the
mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections.
Our results provide a link between quinone and antimicrobial resistance
the MhqR regulon of
.
The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of
under long-term infections.</description><subject>Aldehydes</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial agents</subject><subject>Antimicrobial resistance</subject><subject>Ciprofloxacin</subject><subject>Deletion mutant</subject><subject>Drug resistance</subject><subject>Gene deletion</subject><subject>Gene expression</subject><subject>Homology</subject><subject>Hypochlorous acid</subject><subject>Infections</subject><subject>Inverted repeat</subject><subject>Macrophages</subject><subject>Norfloxacin</subject><subject>Original Research Communications</subject><subject>Oxidants</subject><subject>Oxidizing agents</subject><subject>Penicillin</subject><subject>Pyocyanin</subject><subject>Quinones</subject><subject>Reactive oxygen species</subject><subject>Regulatory mechanisms (biology)</subject><subject>Rifampin</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus infections</subject><subject>Virulence</subject><issn>1523-0864</issn><issn>1557-7716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkc1r4zAQxUXp0o_sHnstgp6dzli25VwKJfQLWpbN5i5kebxRSCRXsgv576uQbmlPI-Y9PT30Y-wCYYpQz651iNMccDaVsoQjdoZlKTMpsTren3ORQV0Vp-w8xjUA5Ihwwk4FCoSknrFmuSL-osMiW-564gvqA8XoA39ZvS743LuOQuR_Ruu8I65dy2_dYLfWBN9YvUkXoo2Ddoa4dfzvoPvVbuONN2aMXI-BxviT_ej0JtKvjzlhy_u75fwxe_798DS_fc6MkNWQyaIwICog2RkjAVvR6llZVYgFyUZK2ZgKBXR13hZd3lDZAhXUGkSqtenEhN0cYvux2aY9uSHojeqD3eqwU15b9V1xdqX--TdVyVldI6SAq4-A4F9HioNa-zG4VFnlAmQOAlKBCcsOrvQDMQbqPl9AUHsiKhFReyJqTyT5L7_W-nT_RyDeAa0WiRo</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Fritsch, Verena Nadin</creator><creator>Loi, Vu Van</creator><creator>Busche, Tobias</creator><creator>Sommer, Anna</creator><creator>Tedin, Karsten</creator><creator>Nürnberg, Dennis J</creator><creator>Kalinowski, Jörn</creator><creator>Bernhardt, Jörg</creator><creator>Fulde, Marcus</creator><creator>Antelmann, Haike</creator><general>Mary Ann Liebert, Inc</general><general>Mary Ann Liebert, Inc., publishers</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20191201</creationdate><title>The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus</title><author>Fritsch, Verena Nadin ; Loi, Vu Van ; Busche, Tobias ; Sommer, Anna ; Tedin, Karsten ; Nürnberg, Dennis J ; Kalinowski, Jörn ; Bernhardt, Jörg ; Fulde, Marcus ; Antelmann, Haike</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-744c0360e7fcc701d3da9566114e7b777bc6130f82d4f2be5d0e4edc11e8acf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aldehydes</topic><topic>Antiinfectives and antibacterials</topic><topic>Antimicrobial agents</topic><topic>Antimicrobial resistance</topic><topic>Ciprofloxacin</topic><topic>Deletion mutant</topic><topic>Drug resistance</topic><topic>Gene deletion</topic><topic>Gene expression</topic><topic>Homology</topic><topic>Hypochlorous acid</topic><topic>Infections</topic><topic>Inverted repeat</topic><topic>Macrophages</topic><topic>Norfloxacin</topic><topic>Original Research Communications</topic><topic>Oxidants</topic><topic>Oxidizing agents</topic><topic>Penicillin</topic><topic>Pyocyanin</topic><topic>Quinones</topic><topic>Reactive oxygen species</topic><topic>Regulatory mechanisms (biology)</topic><topic>Rifampin</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus infections</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fritsch, Verena Nadin</creatorcontrib><creatorcontrib>Loi, Vu Van</creatorcontrib><creatorcontrib>Busche, Tobias</creatorcontrib><creatorcontrib>Sommer, Anna</creatorcontrib><creatorcontrib>Tedin, Karsten</creatorcontrib><creatorcontrib>Nürnberg, Dennis J</creatorcontrib><creatorcontrib>Kalinowski, Jörn</creatorcontrib><creatorcontrib>Bernhardt, Jörg</creatorcontrib><creatorcontrib>Fulde, Marcus</creatorcontrib><creatorcontrib>Antelmann, Haike</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antioxidants & redox signaling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fritsch, Verena Nadin</au><au>Loi, Vu Van</au><au>Busche, Tobias</au><au>Sommer, Anna</au><au>Tedin, Karsten</au><au>Nürnberg, Dennis J</au><au>Kalinowski, Jörn</au><au>Bernhardt, Jörg</au><au>Fulde, Marcus</au><au>Antelmann, Haike</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus</atitle><jtitle>Antioxidants & redox signaling</jtitle><addtitle>Antioxid Redox Signal</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>31</volume><issue>16</issue><spage>1235</spage><epage>1252</epage><pages>1235-1252</pages><issn>1523-0864</issn><eissn>1557-7716</eissn><abstract>Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen
.
Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the
transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The
operon was most strongly upregulated by MHQ and was renamed as
operon based on its homology to the
locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the
operon, which confers quinone and antimicrobial resistance in
. The
operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9-9 bp inverted repeat (MhqR operator) upstream of the
operon and is inactivated by MHQ
, which does not involve a thiol-based mechanism. In phenotypic assays, the
deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the
mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections.
Our results provide a link between quinone and antimicrobial resistance
the MhqR regulon of
.
The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of
under long-term infections.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>31310152</pmid><doi>10.1089/ars.2019.7750</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| source | Alma/SFX Local Collection |
| subjects | Aldehydes Antiinfectives and antibacterials Antimicrobial agents Antimicrobial resistance Ciprofloxacin Deletion mutant Drug resistance Gene deletion Gene expression Homology Hypochlorous acid Infections Inverted repeat Macrophages Norfloxacin Original Research Communications Oxidants Oxidizing agents Penicillin Pyocyanin Quinones Reactive oxygen species Regulatory mechanisms (biology) Rifampin Staphylococcus aureus Staphylococcus infections Virulence |
| title | The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus |
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