Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis
Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2006-06, Vol.312 (5782), p.1944-1946 |
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| container_end_page | 1946 |
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| container_issue | 5782 |
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| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 312 |
| creator | Gagneux, Sebastien Long, Clara Davis Small, Peter M Van, Tran Schoolnik, Gary K Bohannan, Brendan J.M |
| description | Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates. |
| doi_str_mv | 10.1126/science.1124410 |
| format | Article |
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We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1124410</identifier><identifier>PMID: 16809538</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Amino Acid Substitution ; Antibacterial agents ; Antibiotics ; Antibiotics, Antitubercular - pharmacology ; Antibiotics, Antitubercular - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antituberculars ; Bacteria ; Bacterial diseases ; Bacterial Proteins - genetics ; Biological and medical sciences ; Confidence interval ; DNA-Directed RNA Polymerases - genetics ; Drug resistance ; Drug Resistance, Multiple, Bacterial ; Ecological competition ; Epidemics ; Genetic mutation ; Human bacterial diseases ; Human genetics ; Humans ; Infectious diseases ; Mathematical models ; Medical genetics ; Medical sciences ; Models, Biological ; Multidrug resistant tuberculosis ; Mutation ; Mutation, Missense ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - growth & development ; Pharmacology. Drug treatments ; Rifampin - pharmacology ; Rifampin - therapeutic use ; Tuberculosis ; Tuberculosis and atypical mycobacterial infections ; Tuberculosis, Multidrug-Resistant - drug therapy ; Tuberculosis, Multidrug-Resistant - microbiology</subject><ispartof>Science (American Association for the Advancement of Science), 2006-06, Vol.312 (5782), p.1944-1946</ispartof><rights>Copyright 2006 American Association for the Advancement of Science</rights><rights>2006 INIST-CNRS</rights><rights>Copyright American Association for the Advancement of Science Jun 30, 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-6bce3ab160994b43a6b0d39486709c800116239563b6ec21b8eacb878e4d606d3</citedby><cites>FETCH-LOGICAL-c521t-6bce3ab160994b43a6b0d39486709c800116239563b6ec21b8eacb878e4d606d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3846440$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3846440$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17929536$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16809538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gagneux, Sebastien</creatorcontrib><creatorcontrib>Long, Clara Davis</creatorcontrib><creatorcontrib>Small, Peter M</creatorcontrib><creatorcontrib>Van, Tran</creatorcontrib><creatorcontrib>Schoolnik, Gary K</creatorcontrib><creatorcontrib>Bohannan, Brendan J.M</creatorcontrib><title>Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.</description><subject>Amino Acid Substitution</subject><subject>Antibacterial agents</subject><subject>Antibiotics</subject><subject>Antibiotics, Antitubercular - pharmacology</subject><subject>Antibiotics, Antitubercular - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antituberculars</subject><subject>Bacteria</subject><subject>Bacterial diseases</subject><subject>Bacterial Proteins - genetics</subject><subject>Biological and medical sciences</subject><subject>Confidence interval</subject><subject>DNA-Directed RNA Polymerases - genetics</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>Ecological competition</subject><subject>Epidemics</subject><subject>Genetic mutation</subject><subject>Human bacterial diseases</subject><subject>Human genetics</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Mathematical models</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Multidrug resistant tuberculosis</subject><subject>Mutation</subject><subject>Mutation, Missense</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - growth & development</subject><subject>Pharmacology. Drug treatments</subject><subject>Rifampin - pharmacology</subject><subject>Rifampin - therapeutic use</subject><subject>Tuberculosis</subject><subject>Tuberculosis and atypical mycobacterial infections</subject><subject>Tuberculosis, Multidrug-Resistant - drug therapy</subject><subject>Tuberculosis, Multidrug-Resistant - microbiology</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c-L1DAUB_Aiijuunr2IFkFvdV9-9DU5LoOuwoqg7rkkmVQytM2YpML-975higte5pSE98lLeN-qesngA2Mcr7ILfnb-eJCSwaNqw0C3jeYgHlcbAIGNgq69qJ7lvAegmhZPqwuGirZCbaqbbZwOvoQS_vh6G3Op41BfzyXYEEtw9XefQy6G3qjDXH-9d9EaV3wKy1SXxfrkljESeV49GcyY_Yt1vazuPn38uf3c3H67-bK9vm1cy1lp0DovjGUIWksrhUELO6Glwg60UwCMIRe6RWHRO86s8sZZ1Skvdwi4E5fV-1PfQ4q_F59LP4Xs_Dia2ccl96gQQDJ5FgrkSGPiZyGnL-kW2FnIOvo5dILg2__gPi5pprFQM4EMO64IXZ2QSzHn5If-kMJk0n3PoD9m26_Z9mu2dOP12naxk989-DVMAu9WYLIz45AotpAfXKc5OST36uT2ucT0ry6URCmP77w5lQcTe_MrUYu7H5wGAAyItFz8Bca2viY</recordid><startdate>20060630</startdate><enddate>20060630</enddate><creator>Gagneux, Sebastien</creator><creator>Long, Clara Davis</creator><creator>Small, Peter M</creator><creator>Van, Tran</creator><creator>Schoolnik, Gary K</creator><creator>Bohannan, Brendan J.M</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</scope><scope>IQODW</scope><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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20060630</creationdate><title>Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis</title><author>Gagneux, Sebastien ; Long, Clara Davis ; Small, Peter M ; Van, Tran ; Schoolnik, Gary K ; Bohannan, Brendan J.M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-6bce3ab160994b43a6b0d39486709c800116239563b6ec21b8eacb878e4d606d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Amino Acid Substitution</topic><topic>Antibacterial agents</topic><topic>Antibiotics</topic><topic>Antibiotics, Antitubercular - pharmacology</topic><topic>Antibiotics, Antitubercular - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antituberculars</topic><topic>Bacteria</topic><topic>Bacterial diseases</topic><topic>Bacterial Proteins - genetics</topic><topic>Biological and medical sciences</topic><topic>Confidence interval</topic><topic>DNA-Directed RNA Polymerases - genetics</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>Ecological competition</topic><topic>Epidemics</topic><topic>Genetic mutation</topic><topic>Human bacterial diseases</topic><topic>Human genetics</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Mathematical models</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>Multidrug resistant tuberculosis</topic><topic>Mutation</topic><topic>Mutation, Missense</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - drug effects</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - growth & development</topic><topic>Pharmacology. Drug treatments</topic><topic>Rifampin - pharmacology</topic><topic>Rifampin - therapeutic use</topic><topic>Tuberculosis</topic><topic>Tuberculosis and atypical mycobacterial infections</topic><topic>Tuberculosis, Multidrug-Resistant - drug therapy</topic><topic>Tuberculosis, Multidrug-Resistant - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gagneux, Sebastien</creatorcontrib><creatorcontrib>Long, Clara Davis</creatorcontrib><creatorcontrib>Small, Peter M</creatorcontrib><creatorcontrib>Van, Tran</creatorcontrib><creatorcontrib>Schoolnik, Gary K</creatorcontrib><creatorcontrib>Bohannan, Brendan J.M</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gagneux, Sebastien</au><au>Long, Clara Davis</au><au>Small, Peter M</au><au>Van, Tran</au><au>Schoolnik, Gary K</au><au>Bohannan, Brendan J.M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2006-06-30</date><risdate>2006</risdate><volume>312</volume><issue>5782</issue><spage>1944</spage><epage>1946</epage><pages>1944-1946</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>16809538</pmid><doi>10.1126/science.1124410</doi><tpages>3</tpages></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2006-06, Vol.312 (5782), p.1944-1946 |
| issn | 0036-8075 1095-9203 |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Amino Acid Substitution Antibacterial agents Antibiotics Antibiotics, Antitubercular - pharmacology Antibiotics, Antitubercular - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antituberculars Bacteria Bacterial diseases Bacterial Proteins - genetics Biological and medical sciences Confidence interval DNA-Directed RNA Polymerases - genetics Drug resistance Drug Resistance, Multiple, Bacterial Ecological competition Epidemics Genetic mutation Human bacterial diseases Human genetics Humans Infectious diseases Mathematical models Medical genetics Medical sciences Models, Biological Multidrug resistant tuberculosis Mutation Mutation, Missense Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - growth & development Pharmacology. Drug treatments Rifampin - pharmacology Rifampin - therapeutic use Tuberculosis Tuberculosis and atypical mycobacterial infections Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - microbiology |
| title | Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosis |
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