Characterization of a novel antibacterial agent that inhibits bacterial translation
Bacterial protein synthesis is the target for several classes of established antibiotics. This report describes the characterization of a novel translation inhibitor produced by the soil bacterium Flexibacter. The dipeptide antibiotic TAN1057 A/B was synthesized and designated GS7128. As reported pr...
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| Veröffentlicht in: | RNA (Cambridge) 2002-09, Vol.8 (9), p.1120-1128, Article S1355838202024020 |
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| creator | BÖDDEKER, NINA BAHADOR, GINA GIBBS, CRAIG MABERY, ERIC WOLF, JOHN XU, LIANHONG WATSON, JULIA |
| description | Bacterial protein synthesis is the target for several classes
of established antibiotics. This report describes the
characterization of a novel translation inhibitor produced by
the soil bacterium Flexibacter. The dipeptide antibiotic
TAN1057 A/B was synthesized and designated GS7128. As reported
previously, TAN1057 inhibits protein synthesis in both
Escherichia coli and Staphylococcus aureus,
leaving transcription unaffected. Cell-free translation systems
from E. coli were used to further dissect the mechanism
of translational inhibition. Binding of mRNA to ribosomes was
unaffected by the drug, whereas the initiation reaction was
reduced. Elongation of translation was completely inhibited
by GS7128. Detailed analysis showed that the peptidyl transferase
reaction was strongly inhibited, whereas tRNA binding to both
A- and P-site was unaffected. Selection and analysis of
drug-resistant mutants of S. aureus suggests that drug
uptake may be mediated by a dipeptide transport mechanism. |
| doi_str_mv | 10.1017/S1355838202024020 |
| format | Article |
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of established antibiotics. This report describes the
characterization of a novel translation inhibitor produced by
the soil bacterium Flexibacter. The dipeptide antibiotic
TAN1057 A/B was synthesized and designated GS7128. As reported
previously, TAN1057 inhibits protein synthesis in both
Escherichia coli and Staphylococcus aureus,
leaving transcription unaffected. Cell-free translation systems
from E. coli were used to further dissect the mechanism
of translational inhibition. Binding of mRNA to ribosomes was
unaffected by the drug, whereas the initiation reaction was
reduced. Elongation of translation was completely inhibited
by GS7128. Detailed analysis showed that the peptidyl transferase
reaction was strongly inhibited, whereas tRNA binding to both
A- and P-site was unaffected. Selection and analysis of
drug-resistant mutants of S. aureus suggests that drug
uptake may be mediated by a dipeptide transport mechanism.</description><identifier>ISSN: 1355-8382</identifier><identifier>EISSN: 1469-9001</identifier><identifier>DOI: 10.1017/S1355838202024020</identifier><identifier>PMID: 12358431</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Animals ; Anti-Bacterial Agents - biosynthesis ; Anti-Bacterial Agents - isolation & purification ; Anti-Bacterial Agents - pharmacology ; Bacteria - metabolism ; Culture Media ; Dipeptides - biosynthesis ; Dipeptides - isolation & purification ; Dipeptides - pharmacology ; Drug Resistance, Bacterial ; Enzyme Inhibitors - isolation & purification ; Enzyme Inhibitors - pharmacology ; Escherichia coli - drug effects ; Escherichia coli - genetics ; Escherichia coli - metabolism ; In Vitro Techniques ; Peptide Chain Elongation, Translational - drug effects ; Peptide Chain Initiation, Translational - drug effects ; Peptidyl Transferases - antagonists & inhibitors ; Protein Biosynthesis - drug effects ; Protein Synthesis Inhibitors - isolation & purification ; Protein Synthesis Inhibitors - pharmacology ; Rabbits ; RNA, Transfer, Phe - metabolism ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - genetics ; Staphylococcus aureus - metabolism</subject><ispartof>RNA (Cambridge), 2002-09, Vol.8 (9), p.1120-1128, Article S1355838202024020</ispartof><rights>2002 RNA Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-6f69e98f9d31b2168f2f066164318551fde27a1d19a06f845e6d87a4ebbbf1883</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370326/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370326/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12358431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BÖDDEKER, NINA</creatorcontrib><creatorcontrib>BAHADOR, GINA</creatorcontrib><creatorcontrib>GIBBS, CRAIG</creatorcontrib><creatorcontrib>MABERY, ERIC</creatorcontrib><creatorcontrib>WOLF, JOHN</creatorcontrib><creatorcontrib>XU, LIANHONG</creatorcontrib><creatorcontrib>WATSON, JULIA</creatorcontrib><title>Characterization of a novel antibacterial agent that inhibits bacterial translation</title><title>RNA (Cambridge)</title><addtitle>RNA</addtitle><description>Bacterial protein synthesis is the target for several classes
of established antibiotics. This report describes the
characterization of a novel translation inhibitor produced by
the soil bacterium Flexibacter. The dipeptide antibiotic
TAN1057 A/B was synthesized and designated GS7128. As reported
previously, TAN1057 inhibits protein synthesis in both
Escherichia coli and Staphylococcus aureus,
leaving transcription unaffected. Cell-free translation systems
from E. coli were used to further dissect the mechanism
of translational inhibition. Binding of mRNA to ribosomes was
unaffected by the drug, whereas the initiation reaction was
reduced. Elongation of translation was completely inhibited
by GS7128. Detailed analysis showed that the peptidyl transferase
reaction was strongly inhibited, whereas tRNA binding to both
A- and P-site was unaffected. Selection and analysis of
drug-resistant mutants of S. aureus suggests that drug
uptake may be mediated by a dipeptide transport mechanism.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - biosynthesis</subject><subject>Anti-Bacterial Agents - isolation & purification</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Bacteria - metabolism</subject><subject>Culture Media</subject><subject>Dipeptides - biosynthesis</subject><subject>Dipeptides - isolation & purification</subject><subject>Dipeptides - pharmacology</subject><subject>Drug Resistance, Bacterial</subject><subject>Enzyme Inhibitors - isolation & purification</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Escherichia coli - drug effects</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - metabolism</subject><subject>In Vitro Techniques</subject><subject>Peptide Chain Elongation, Translational - drug effects</subject><subject>Peptide Chain Initiation, Translational - drug effects</subject><subject>Peptidyl Transferases - antagonists & inhibitors</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Protein Synthesis Inhibitors - isolation & purification</subject><subject>Protein Synthesis Inhibitors - pharmacology</subject><subject>Rabbits</subject><subject>RNA, Transfer, Phe - metabolism</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus aureus - genetics</subject><subject>Staphylococcus aureus - metabolism</subject><issn>1355-8382</issn><issn>1469-9001</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtLxDAUhYMojq8f4Ea6clfNbdo03Qgy-ALBhboOt20yk6GTaJIR9NebcQYfCEogr3Pux0kuIYdAT4BCfXoPrKoEEwVNo0zTBtmBkjd5Qylspn2S86U-IrshzNIlS_I2GUHBKlEy2CH34yl67KLy5g2jcTZzOsPMuhc1ZGijaVciptNE2ZjFKcbM2KlpTQzZlxo92jB8IPbJlsYhqIP1ukceLy8extf57d3Vzfj8Nu8qEDHnmjeqEbrpGbQFcKELTTkHnoKJqgLdq6JG6KFByrUoK8V7UWOp2rbVIATbI2cr7tOinau-S_E8DvLJmzn6V-nQyJ-KNVM5cS8SWE1ZwRPgeA3w7nmhQpRzEzo1DGiVWwRZF8nJBf3XuMxbVDVLRlgZO-9C8Ep_pgEqlz2Tv3qWao6-P-OrYt2kZGBrKM5bb_qJkjO38Db97R_Yd-pfol0</recordid><startdate>200209</startdate><enddate>200209</enddate><creator>BÖDDEKER, NINA</creator><creator>BAHADOR, GINA</creator><creator>GIBBS, CRAIG</creator><creator>MABERY, ERIC</creator><creator>WOLF, JOHN</creator><creator>XU, LIANHONG</creator><creator>WATSON, JULIA</creator><general>Cambridge University Press</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>7T7</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200209</creationdate><title>Characterization of a novel antibacterial agent that inhibits bacterial translation</title><author>BÖDDEKER, NINA ; BAHADOR, GINA ; GIBBS, CRAIG ; MABERY, ERIC ; WOLF, JOHN ; XU, LIANHONG ; WATSON, JULIA</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-6f69e98f9d31b2168f2f066164318551fde27a1d19a06f845e6d87a4ebbbf1883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - biosynthesis</topic><topic>Anti-Bacterial Agents - isolation & purification</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Bacteria - metabolism</topic><topic>Culture Media</topic><topic>Dipeptides - biosynthesis</topic><topic>Dipeptides - isolation & purification</topic><topic>Dipeptides - pharmacology</topic><topic>Drug Resistance, Bacterial</topic><topic>Enzyme Inhibitors - isolation & purification</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Escherichia coli - drug effects</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - metabolism</topic><topic>In Vitro Techniques</topic><topic>Peptide Chain Elongation, Translational - drug effects</topic><topic>Peptide Chain Initiation, Translational - drug effects</topic><topic>Peptidyl Transferases - antagonists & inhibitors</topic><topic>Protein Biosynthesis - drug effects</topic><topic>Protein Synthesis Inhibitors - isolation & purification</topic><topic>Protein Synthesis Inhibitors - pharmacology</topic><topic>Rabbits</topic><topic>RNA, Transfer, Phe - metabolism</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Staphylococcus aureus - genetics</topic><topic>Staphylococcus aureus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BÖDDEKER, NINA</creatorcontrib><creatorcontrib>BAHADOR, GINA</creatorcontrib><creatorcontrib>GIBBS, CRAIG</creatorcontrib><creatorcontrib>MABERY, ERIC</creatorcontrib><creatorcontrib>WOLF, JOHN</creatorcontrib><creatorcontrib>XU, LIANHONG</creatorcontrib><creatorcontrib>WATSON, JULIA</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RNA (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BÖDDEKER, NINA</au><au>BAHADOR, GINA</au><au>GIBBS, CRAIG</au><au>MABERY, ERIC</au><au>WOLF, JOHN</au><au>XU, LIANHONG</au><au>WATSON, JULIA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of a novel antibacterial agent that inhibits bacterial translation</atitle><jtitle>RNA (Cambridge)</jtitle><addtitle>RNA</addtitle><date>2002-09</date><risdate>2002</risdate><volume>8</volume><issue>9</issue><spage>1120</spage><epage>1128</epage><pages>1120-1128</pages><artnum>S1355838202024020</artnum><issn>1355-8382</issn><eissn>1469-9001</eissn><abstract>Bacterial protein synthesis is the target for several classes
of established antibiotics. This report describes the
characterization of a novel translation inhibitor produced by
the soil bacterium Flexibacter. The dipeptide antibiotic
TAN1057 A/B was synthesized and designated GS7128. As reported
previously, TAN1057 inhibits protein synthesis in both
Escherichia coli and Staphylococcus aureus,
leaving transcription unaffected. Cell-free translation systems
from E. coli were used to further dissect the mechanism
of translational inhibition. Binding of mRNA to ribosomes was
unaffected by the drug, whereas the initiation reaction was
reduced. Elongation of translation was completely inhibited
by GS7128. Detailed analysis showed that the peptidyl transferase
reaction was strongly inhibited, whereas tRNA binding to both
A- and P-site was unaffected. Selection and analysis of
drug-resistant mutants of S. aureus suggests that drug
uptake may be mediated by a dipeptide transport mechanism.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>12358431</pmid><doi>10.1017/S1355838202024020</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Anti-Bacterial Agents - biosynthesis Anti-Bacterial Agents - isolation & purification Anti-Bacterial Agents - pharmacology Bacteria - metabolism Culture Media Dipeptides - biosynthesis Dipeptides - isolation & purification Dipeptides - pharmacology Drug Resistance, Bacterial Enzyme Inhibitors - isolation & purification Enzyme Inhibitors - pharmacology Escherichia coli - drug effects Escherichia coli - genetics Escherichia coli - metabolism In Vitro Techniques Peptide Chain Elongation, Translational - drug effects Peptide Chain Initiation, Translational - drug effects Peptidyl Transferases - antagonists & inhibitors Protein Biosynthesis - drug effects Protein Synthesis Inhibitors - isolation & purification Protein Synthesis Inhibitors - pharmacology Rabbits RNA, Transfer, Phe - metabolism Staphylococcus aureus - drug effects Staphylococcus aureus - genetics Staphylococcus aureus - metabolism |
| title | Characterization of a novel antibacterial agent that inhibits bacterial translation |
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