In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance
Bedaquiline resistance within may arise through efflux-based ( ) or target-based ( ) pathway mutations. mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposur...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy 2019-08, Vol.63 (8) |
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| container_title | Antimicrobial agents and chemotherapy |
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| creator | Ismail, Nabila Ismail, Nazir A Omar, Shaheed V Peters, Remco P H |
| description | Bedaquiline resistance within
may arise through efflux-based (
) or target-based (
) pathway mutations.
mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposure to increasing bedaquiline concentrations resulted in increasing phenotypic resistance (up to >2 μg/ml) through MIC determination on solid medium (Middlebrook 7H10).
mutations were dynamic, while
mutations were fixed, once occurring. We present the following hypothesis for
emergence of bedaquiline resistance:
mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed
mutations. |
| doi_str_mv | 10.1128/AAC.00292-19 |
| format | Article |
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may arise through efflux-based (
) or target-based (
) pathway mutations.
mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposure to increasing bedaquiline concentrations resulted in increasing phenotypic resistance (up to >2 μg/ml) through MIC determination on solid medium (Middlebrook 7H10).
mutations were dynamic, while
mutations were fixed, once occurring. We present the following hypothesis for
emergence of bedaquiline resistance:
mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed
mutations.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.00292-19</identifier><identifier>PMID: 31138569</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Bacterial Proteins ; Diarylquinolines ; Drug Resistance, Bacterial ; Mechanisms of Resistance ; Mutation ; Mycobacterium tuberculosis</subject><ispartof>Antimicrobial agents and chemotherapy, 2019-08, Vol.63 (8)</ispartof><rights>Copyright © 2019 American Society for Microbiology.</rights><rights>Copyright © 2019 American Society for Microbiology. 2019 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a418t-a08f045df1c1d448830eebd81ef228b38d939ccf433c63498e4b8d0f5e8ab0993</citedby><cites>FETCH-LOGICAL-a418t-a08f045df1c1d448830eebd81ef228b38d939ccf433c63498e4b8d0f5e8ab0993</cites><orcidid>0000-0002-2287-1857 ; 0000-0003-2124-7275</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658778/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658778/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31138569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ismail, Nabila</creatorcontrib><creatorcontrib>Ismail, Nazir A</creatorcontrib><creatorcontrib>Omar, Shaheed V</creatorcontrib><creatorcontrib>Peters, Remco P H</creatorcontrib><title>In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Bedaquiline resistance within
may arise through efflux-based (
) or target-based (
) pathway mutations.
mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposure to increasing bedaquiline concentrations resulted in increasing phenotypic resistance (up to >2 μg/ml) through MIC determination on solid medium (Middlebrook 7H10).
mutations were dynamic, while
mutations were fixed, once occurring. We present the following hypothesis for
emergence of bedaquiline resistance:
mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed
mutations.</description><subject>Bacterial Proteins</subject><subject>Diarylquinolines</subject><subject>Drug Resistance, Bacterial</subject><subject>Mechanisms of Resistance</subject><subject>Mutation</subject><subject>Mycobacterium tuberculosis</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1Uc9PHCEUJqaNbq03z4Zjm3QUBoaFS5N1Y1sTjYltvRIGHhYzCyswNv73znatqYee3q_vfe_Hh9AhJceUtvJksVgeE9KqtqFqB80oUbIRnRJv0IwQIRouCd9D70q5I1PcKbKL9hilTHZCzRCcR3wTak74ex3dI05-cmD9OxTAC3s_hhJqSHGTzw9EzCU20WFT12f4cqxmUyt4maKHnEO8xafgzNQ1hAj4Gkoo1UQL79Fbb4YCB892H_38cvZj-a25uPp6vlxcNIZTWRtDpCe8c55a6jiXkhGA3kkKvm1lz6RTTFnrOWNWMK4k8F464juQpidKsX30ecu7HvsVOAuxZjPodQ4rkx91MkG_rsTwS9-mBy1EJ-dzORF8eCbI6X6EUvUqFAvDYCKksei2ZXR6XMe6CfppC7U5lZLBv4yhRG-U0ZMy-o8ymm5W-7iFm7Jq9V0ac5w-8T_s0b9nvBD_lY09ARmeluM</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Ismail, Nabila</creator><creator>Ismail, Nazir A</creator><creator>Omar, Shaheed V</creator><creator>Peters, Remco P H</creator><general>American Society for Microbiology</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2287-1857</orcidid><orcidid>https://orcid.org/0000-0003-2124-7275</orcidid></search><sort><creationdate>20190801</creationdate><title>In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance</title><author>Ismail, Nabila ; Ismail, Nazir A ; Omar, Shaheed V ; Peters, Remco P H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a418t-a08f045df1c1d448830eebd81ef228b38d939ccf433c63498e4b8d0f5e8ab0993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Bacterial Proteins</topic><topic>Diarylquinolines</topic><topic>Drug Resistance, Bacterial</topic><topic>Mechanisms of Resistance</topic><topic>Mutation</topic><topic>Mycobacterium tuberculosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ismail, Nabila</creatorcontrib><creatorcontrib>Ismail, Nazir A</creatorcontrib><creatorcontrib>Omar, Shaheed V</creatorcontrib><creatorcontrib>Peters, Remco P H</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ismail, Nabila</au><au>Ismail, Nazir A</au><au>Omar, Shaheed V</au><au>Peters, Remco P H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>63</volume><issue>8</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Bedaquiline resistance within
may arise through efflux-based (
) or target-based (
) pathway mutations.
mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposure to increasing bedaquiline concentrations resulted in increasing phenotypic resistance (up to >2 μg/ml) through MIC determination on solid medium (Middlebrook 7H10).
mutations were dynamic, while
mutations were fixed, once occurring. We present the following hypothesis for
emergence of bedaquiline resistance:
mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed
mutations.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>31138569</pmid><doi>10.1128/AAC.00292-19</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-2287-1857</orcidid><orcidid>https://orcid.org/0000-0003-2124-7275</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Antimicrobial agents and chemotherapy, 2019-08, Vol.63 (8) |
| issn | 0066-4804 1098-6596 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6658778 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Bacterial Proteins Diarylquinolines Drug Resistance, Bacterial Mechanisms of Resistance Mutation Mycobacterium tuberculosis |
| title | In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance |
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