Distribution and infection-related functions of bacillithiol in Staphylococcus aureus
Abstract Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine B...
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| Veröffentlicht in: | International journal of medical microbiology 2013-04, Vol.303 (3), p.114-123 |
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| creator | Pöther, Dierk-Christoph Gierok, Philipp Harms, Manuela Mostertz, Jörg Hochgräfe, Falko Antelmann, Haike Hamilton, Chris J Borovok, Ilya Lalk, Michael Aharonowitz, Yair Hecker, Michael |
| description | Abstract Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117–1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC -gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection. |
| doi_str_mv | 10.1016/j.ijmm.2013.01.003 |
| format | Article |
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These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117–1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC -gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection.</description><identifier>ISSN: 1438-4221</identifier><identifier>EISSN: 1618-0607</identifier><identifier>DOI: 10.1016/j.ijmm.2013.01.003</identifier><identifier>PMID: 23517692</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Animals ; Anti-Bacterial Agents - pharmacology ; Antioxidants ; Bacillithiol ; Bacillus ; Bacterial Load ; bshC ; Cell Line ; Chromatography, High Pressure Liquid ; Cysteine - analogs & derivatives ; Cysteine - biosynthesis ; Cysteine - genetics ; Diamide - pharmacology ; Drug Resistance, Bacterial ; Epithelial Cells - microbiology ; Fosfomycin - pharmacology ; Gene Expression ; Glucosamine - analogs & derivatives ; Glucosamine - biosynthesis ; Glucosamine - genetics ; Glutathione ; Humans ; Hydrogen Peroxide - pharmacology ; Hypochlorous Acid - pharmacology ; Infectious Disease ; Low molecular weight thiol ; Macrophages - microbiology ; Medical Education ; Mice ; Oxidants - pharmacology ; Staphylococcus aureus ; Staphylococcus aureus - chemistry ; Staphylococcus aureus - genetics ; Staphylococcus aureus - metabolism ; Staphylococcus aureus - pathogenicity ; Virulence Factors - biosynthesis ; Virulence Factors - genetics</subject><ispartof>International journal of medical microbiology, 2013-04, Vol.303 (3), p.114-123</ispartof><rights>Elsevier GmbH</rights><rights>2013 Elsevier GmbH</rights><rights>Copyright © 2013 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-d3c2500e28fe10c2aa7e4bcf982155d2c5edb7fbb1f8293933fa3f73743f9a3c3</citedby><cites>FETCH-LOGICAL-c444t-d3c2500e28fe10c2aa7e4bcf982155d2c5edb7fbb1f8293933fa3f73743f9a3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1438422113000337$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23517692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pöther, Dierk-Christoph</creatorcontrib><creatorcontrib>Gierok, Philipp</creatorcontrib><creatorcontrib>Harms, Manuela</creatorcontrib><creatorcontrib>Mostertz, Jörg</creatorcontrib><creatorcontrib>Hochgräfe, Falko</creatorcontrib><creatorcontrib>Antelmann, Haike</creatorcontrib><creatorcontrib>Hamilton, Chris J</creatorcontrib><creatorcontrib>Borovok, Ilya</creatorcontrib><creatorcontrib>Lalk, Michael</creatorcontrib><creatorcontrib>Aharonowitz, Yair</creatorcontrib><creatorcontrib>Hecker, Michael</creatorcontrib><title>Distribution and infection-related functions of bacillithiol in Staphylococcus aureus</title><title>International journal of medical microbiology</title><addtitle>Int J Med Microbiol</addtitle><description>Abstract Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117–1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC -gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antioxidants</subject><subject>Bacillithiol</subject><subject>Bacillus</subject><subject>Bacterial Load</subject><subject>bshC</subject><subject>Cell Line</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cysteine - analogs & derivatives</subject><subject>Cysteine - biosynthesis</subject><subject>Cysteine - genetics</subject><subject>Diamide - pharmacology</subject><subject>Drug Resistance, Bacterial</subject><subject>Epithelial Cells - microbiology</subject><subject>Fosfomycin - pharmacology</subject><subject>Gene Expression</subject><subject>Glucosamine - analogs & derivatives</subject><subject>Glucosamine - biosynthesis</subject><subject>Glucosamine - genetics</subject><subject>Glutathione</subject><subject>Humans</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Hypochlorous Acid - pharmacology</subject><subject>Infectious Disease</subject><subject>Low molecular weight thiol</subject><subject>Macrophages - microbiology</subject><subject>Medical Education</subject><subject>Mice</subject><subject>Oxidants - pharmacology</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - chemistry</subject><subject>Staphylococcus aureus - genetics</subject><subject>Staphylococcus aureus - metabolism</subject><subject>Staphylococcus aureus - pathogenicity</subject><subject>Virulence Factors - biosynthesis</subject><subject>Virulence Factors - genetics</subject><issn>1438-4221</issn><issn>1618-0607</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2L1TAUhosozof-ARfSpZvWc5K2aUEEGXUUBlyMsw5pesKkps01aYT77029owsXusoHz_uSPKcoXiDUCNi9nms7L0vNAHkNWAPwR8U5dthX0IF4nPcN76uGMTwrLmKcAYANvHtanDHeougGdl7cvbdxC3ZMm_VrqdaptKshvZ-qQE5tNJUmrb8uYulNOSptnbPbvfUus-Xtpg73R-e11zrFUqVAKT4rnhjlIj1_WC-Lu48fvl59qm6-XH--endT6aZptmrimrUAxHpDCJopJagZtRl6hm07Md3SNAozjmj6_PKBc6O4EVw03AyKa35ZvDr1HoL_nihucrFRk3NqJZ-iRN6Jpu_2b_8fZS3nDARmlJ1QHXyMgYw8BLuocJQIcjcvZ7mbl7t5CSiz-Rx6-dCfxoWmP5HfqjPw5gRQFvLDUpBRW1o1TTZk4XLy9t_9b_-Ka2dXq5X7RkeKs09hzaolysgkyNt99vvokcMeF_wnZkyqVw</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Pöther, Dierk-Christoph</creator><creator>Gierok, Philipp</creator><creator>Harms, Manuela</creator><creator>Mostertz, Jörg</creator><creator>Hochgräfe, Falko</creator><creator>Antelmann, Haike</creator><creator>Hamilton, Chris J</creator><creator>Borovok, Ilya</creator><creator>Lalk, Michael</creator><creator>Aharonowitz, Yair</creator><creator>Hecker, Michael</creator><general>Elsevier GmbH</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>7QL</scope><scope>C1K</scope></search><sort><creationdate>20130401</creationdate><title>Distribution and infection-related functions of bacillithiol in Staphylococcus aureus</title><author>Pöther, Dierk-Christoph ; Gierok, Philipp ; Harms, Manuela ; Mostertz, Jörg ; Hochgräfe, Falko ; Antelmann, Haike ; Hamilton, Chris J ; Borovok, Ilya ; Lalk, Michael ; Aharonowitz, Yair ; Hecker, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-d3c2500e28fe10c2aa7e4bcf982155d2c5edb7fbb1f8293933fa3f73743f9a3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antioxidants</topic><topic>Bacillithiol</topic><topic>Bacillus</topic><topic>Bacterial Load</topic><topic>bshC</topic><topic>Cell Line</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Cysteine - analogs & derivatives</topic><topic>Cysteine - biosynthesis</topic><topic>Cysteine - genetics</topic><topic>Diamide - pharmacology</topic><topic>Drug Resistance, Bacterial</topic><topic>Epithelial Cells - microbiology</topic><topic>Fosfomycin - pharmacology</topic><topic>Gene Expression</topic><topic>Glucosamine - analogs & derivatives</topic><topic>Glucosamine - biosynthesis</topic><topic>Glucosamine - genetics</topic><topic>Glutathione</topic><topic>Humans</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Hypochlorous Acid - pharmacology</topic><topic>Infectious Disease</topic><topic>Low molecular weight thiol</topic><topic>Macrophages - microbiology</topic><topic>Medical Education</topic><topic>Mice</topic><topic>Oxidants - pharmacology</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - chemistry</topic><topic>Staphylococcus aureus - genetics</topic><topic>Staphylococcus aureus - metabolism</topic><topic>Staphylococcus aureus - pathogenicity</topic><topic>Virulence Factors - biosynthesis</topic><topic>Virulence Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pöther, Dierk-Christoph</creatorcontrib><creatorcontrib>Gierok, Philipp</creatorcontrib><creatorcontrib>Harms, Manuela</creatorcontrib><creatorcontrib>Mostertz, Jörg</creatorcontrib><creatorcontrib>Hochgräfe, Falko</creatorcontrib><creatorcontrib>Antelmann, Haike</creatorcontrib><creatorcontrib>Hamilton, Chris J</creatorcontrib><creatorcontrib>Borovok, Ilya</creatorcontrib><creatorcontrib>Lalk, Michael</creatorcontrib><creatorcontrib>Aharonowitz, Yair</creatorcontrib><creatorcontrib>Hecker, Michael</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>International journal of medical microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pöther, Dierk-Christoph</au><au>Gierok, Philipp</au><au>Harms, Manuela</au><au>Mostertz, Jörg</au><au>Hochgräfe, Falko</au><au>Antelmann, Haike</au><au>Hamilton, Chris J</au><au>Borovok, Ilya</au><au>Lalk, Michael</au><au>Aharonowitz, Yair</au><au>Hecker, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distribution and infection-related functions of bacillithiol in Staphylococcus aureus</atitle><jtitle>International journal of medical microbiology</jtitle><addtitle>Int J Med Microbiol</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>303</volume><issue>3</issue><spage>114</spage><epage>123</epage><pages>114-123</pages><issn>1438-4221</issn><eissn>1618-0607</eissn><abstract>Abstract Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117–1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC -gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>23517692</pmid><doi>10.1016/j.ijmm.2013.01.003</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Anti-Bacterial Agents - pharmacology Antioxidants Bacillithiol Bacillus Bacterial Load bshC Cell Line Chromatography, High Pressure Liquid Cysteine - analogs & derivatives Cysteine - biosynthesis Cysteine - genetics Diamide - pharmacology Drug Resistance, Bacterial Epithelial Cells - microbiology Fosfomycin - pharmacology Gene Expression Glucosamine - analogs & derivatives Glucosamine - biosynthesis Glucosamine - genetics Glutathione Humans Hydrogen Peroxide - pharmacology Hypochlorous Acid - pharmacology Infectious Disease Low molecular weight thiol Macrophages - microbiology Medical Education Mice Oxidants - pharmacology Staphylococcus aureus Staphylococcus aureus - chemistry Staphylococcus aureus - genetics Staphylococcus aureus - metabolism Staphylococcus aureus - pathogenicity Virulence Factors - biosynthesis Virulence Factors - genetics |
| title | Distribution and infection-related functions of bacillithiol in Staphylococcus aureus |
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