Loading…

The potential target of bithionol against Staphylococcus aureus: design, synthesis and application of biotinylated probes Bio-A2

This study aims to explore the potential targets of bithionol in Staphylococcus aureus .The four bithionol biotinylated probes Bio-A2-1 , Bio-A2-2 , Bio-A2-3 , and Bio-A2-4 were synthesized, the minimal inhibitory concentrations (MICs) of these probes against S. aureus were determined. The bithionol...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antibiotics 2023-07, Vol.76 (7), p.406-415
Main Authors: Luo, Yue, Wen, Zewen, Xiong, Yanpeng, Chen, Xuecheng, Shen, Zonglin, Li, Peiyu, Peng, Yalan, Deng, Qiwen, Yu, Zhijian, Zheng, Jinxin, Han, Shiqing
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333
cites cdi_FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333
container_end_page 415
container_issue 7
container_start_page 406
container_title Journal of antibiotics
container_volume 76
creator Luo, Yue
Wen, Zewen
Xiong, Yanpeng
Chen, Xuecheng
Shen, Zonglin
Li, Peiyu
Peng, Yalan
Deng, Qiwen
Yu, Zhijian
Zheng, Jinxin
Han, Shiqing
description This study aims to explore the potential targets of bithionol in Staphylococcus aureus .The four bithionol biotinylated probes Bio-A2-1 , Bio-A2-2 , Bio-A2-3 , and Bio-A2-4 were synthesized, the minimal inhibitory concentrations (MICs) of these probes against S. aureus were determined. The bithionol binding proteins in S. aureus were identified through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe. The biotinylated bithionol probes Bio-A2-1 and Bio-A2-3 displayed antibacterial activities against S. aureus . The Bio-A2-1 showed lower MICs than Bio-A2-3 , and both with the MIC 50 /MIC 90 at 12.5/12.5 μM against S. aureus clinical isolates. The inhibition rates of bithionol biotinylated probes Bio-A2-1 and Bio-A2-3 on the biofilm formation of S. aureus were comparable to that of bithionol, and were stronger than that of Bio-A2-2 and Bio-A2-4 . The biofilm formation of 10 out of 12 S. aureus clinical isolates could be inhibited by Bio-A2-1 (at 1/4×, or 1/2× MICs). There are three proteins identified in S. aureus through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe Bio-A2-1 : Protein translocase subunit SecA 1 ( secA1 ), Alanine--tRNA ligase ( alaS ) and DNA gyrase subunit A ( gyrA ), and in which the SecA1 protein the highest coverage and the most unique peptides. The LYS112, GLN143, ASP213, GLY496 and ASP498 of SecA1 protein act as hydrogen acceptors to form 6 hydrogen bonds with bithionol biotinylated probe Bio-A2-1 by molecular docking analysis. In conclusion, the bithionol biotinylated probe Bio-A2-1 has antibacterial and anti-biofilm activities against S. aureus , and SecA1 was probably one of the potential targets of bithionol in S. aureus .
doi_str_mv 10.1038/s41429-023-00618-x
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2814524349</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2814524349</sourcerecordid><originalsourceid>FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333</originalsourceid><addsrcrecordid>eNp9kU2LFDEQhoMo7rj6BzxIwIsHo_nq7sTbuvgFCx5cz6E6ncxk6UnaJA07N3-60V4VPHiqFPXUW4EHoaeMvmJUqNdFMsk1oVwQSnumyO09tGNKMcJkr--jHaWcEaU4PUOPSrmhVAxiUA_RmRiY6jrFd-j79cHhJVUXa4AZV8h7V3HyeAz1EFJMM4Y9hFgq_lJhOZzmZJO1a8GwZreWN3hyJezjS1xOsR7au03ihGFZ5mChtogtLdUQTzNUN-Elp9EV_DYkcsEfowce5uKe3NVz9PX9u-vLj-Tq84dPlxdXxAqtK_FCCT2MegQrvZ2AM-Cil6C0BzZYN_Z69N3UOuWtptNIKeso9NY7KagQ4hy92HLb9W-rK9UcQ7FuniG6tBbDFZMdl0Lqhj7_B71Ja47td43iumdSy75RfKNsTqVk582SwxHyyTBqfvoxmx_T_JhffsxtW3p2F72ORzf9WfktpAFiA0obxb3Lf2__J_YH_yueNQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2829614946</pqid></control><display><type>article</type><title>The potential target of bithionol against Staphylococcus aureus: design, synthesis and application of biotinylated probes Bio-A2</title><source>Springer Link</source><creator>Luo, Yue ; Wen, Zewen ; Xiong, Yanpeng ; Chen, Xuecheng ; Shen, Zonglin ; Li, Peiyu ; Peng, Yalan ; Deng, Qiwen ; Yu, Zhijian ; Zheng, Jinxin ; Han, Shiqing</creator><creatorcontrib>Luo, Yue ; Wen, Zewen ; Xiong, Yanpeng ; Chen, Xuecheng ; Shen, Zonglin ; Li, Peiyu ; Peng, Yalan ; Deng, Qiwen ; Yu, Zhijian ; Zheng, Jinxin ; Han, Shiqing</creatorcontrib><description>This study aims to explore the potential targets of bithionol in Staphylococcus aureus .The four bithionol biotinylated probes Bio-A2-1 , Bio-A2-2 , Bio-A2-3 , and Bio-A2-4 were synthesized, the minimal inhibitory concentrations (MICs) of these probes against S. aureus were determined. The bithionol binding proteins in S. aureus were identified through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe. The biotinylated bithionol probes Bio-A2-1 and Bio-A2-3 displayed antibacterial activities against S. aureus . The Bio-A2-1 showed lower MICs than Bio-A2-3 , and both with the MIC 50 /MIC 90 at 12.5/12.5 μM against S. aureus clinical isolates. The inhibition rates of bithionol biotinylated probes Bio-A2-1 and Bio-A2-3 on the biofilm formation of S. aureus were comparable to that of bithionol, and were stronger than that of Bio-A2-2 and Bio-A2-4 . The biofilm formation of 10 out of 12 S. aureus clinical isolates could be inhibited by Bio-A2-1 (at 1/4×, or 1/2× MICs). There are three proteins identified in S. aureus through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe Bio-A2-1 : Protein translocase subunit SecA 1 ( secA1 ), Alanine--tRNA ligase ( alaS ) and DNA gyrase subunit A ( gyrA ), and in which the SecA1 protein the highest coverage and the most unique peptides. The LYS112, GLN143, ASP213, GLY496 and ASP498 of SecA1 protein act as hydrogen acceptors to form 6 hydrogen bonds with bithionol biotinylated probe Bio-A2-1 by molecular docking analysis. In conclusion, the bithionol biotinylated probe Bio-A2-1 has antibacterial and anti-biofilm activities against S. aureus , and SecA1 was probably one of the potential targets of bithionol in S. aureus .</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/s41429-023-00618-x</identifier><identifier>PMID: 37185582</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>631/326/22/1290 ; 631/92/609 ; 692/699/255/1318 ; 82 ; 82/58 ; Alanine ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibacterial activity ; Bacteriology ; Biofilms ; Biomedical and Life Sciences ; Bioorganic Chemistry ; Bithionol ; Chromatography, Liquid ; Clinical isolates ; DNA probes ; DNA topoisomerase ; Humans ; Hydrogen bonding ; Hydrogen bonds ; Immunoprecipitation ; Life Sciences ; Medicinal Chemistry ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests ; Microbiology ; Molecular docking ; Molecular Docking Simulation ; Organic Chemistry ; Peptides ; Probes ; Proteins ; Staphylococcal Infections - microbiology ; Staphylococcus aureus ; Staphylococcus aureus - genetics ; Tandem Mass Spectrometry ; Translocase ; tRNA Ala</subject><ispartof>Journal of antibiotics, 2023-07, Vol.76 (7), p.406-415</ispartof><rights>The Author(s), under exclusive licence to the Japan Antibiotics Research Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333</citedby><cites>FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333</cites><orcidid>0000-0003-4064-2430</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37185582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Yue</creatorcontrib><creatorcontrib>Wen, Zewen</creatorcontrib><creatorcontrib>Xiong, Yanpeng</creatorcontrib><creatorcontrib>Chen, Xuecheng</creatorcontrib><creatorcontrib>Shen, Zonglin</creatorcontrib><creatorcontrib>Li, Peiyu</creatorcontrib><creatorcontrib>Peng, Yalan</creatorcontrib><creatorcontrib>Deng, Qiwen</creatorcontrib><creatorcontrib>Yu, Zhijian</creatorcontrib><creatorcontrib>Zheng, Jinxin</creatorcontrib><creatorcontrib>Han, Shiqing</creatorcontrib><title>The potential target of bithionol against Staphylococcus aureus: design, synthesis and application of biotinylated probes Bio-A2</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>This study aims to explore the potential targets of bithionol in Staphylococcus aureus .The four bithionol biotinylated probes Bio-A2-1 , Bio-A2-2 , Bio-A2-3 , and Bio-A2-4 were synthesized, the minimal inhibitory concentrations (MICs) of these probes against S. aureus were determined. The bithionol binding proteins in S. aureus were identified through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe. The biotinylated bithionol probes Bio-A2-1 and Bio-A2-3 displayed antibacterial activities against S. aureus . The Bio-A2-1 showed lower MICs than Bio-A2-3 , and both with the MIC 50 /MIC 90 at 12.5/12.5 μM against S. aureus clinical isolates. The inhibition rates of bithionol biotinylated probes Bio-A2-1 and Bio-A2-3 on the biofilm formation of S. aureus were comparable to that of bithionol, and were stronger than that of Bio-A2-2 and Bio-A2-4 . The biofilm formation of 10 out of 12 S. aureus clinical isolates could be inhibited by Bio-A2-1 (at 1/4×, or 1/2× MICs). There are three proteins identified in S. aureus through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe Bio-A2-1 : Protein translocase subunit SecA 1 ( secA1 ), Alanine--tRNA ligase ( alaS ) and DNA gyrase subunit A ( gyrA ), and in which the SecA1 protein the highest coverage and the most unique peptides. The LYS112, GLN143, ASP213, GLY496 and ASP498 of SecA1 protein act as hydrogen acceptors to form 6 hydrogen bonds with bithionol biotinylated probe Bio-A2-1 by molecular docking analysis. In conclusion, the bithionol biotinylated probe Bio-A2-1 has antibacterial and anti-biofilm activities against S. aureus , and SecA1 was probably one of the potential targets of bithionol in S. aureus .</description><subject>631/326/22/1290</subject><subject>631/92/609</subject><subject>692/699/255/1318</subject><subject>82</subject><subject>82/58</subject><subject>Alanine</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibacterial activity</subject><subject>Bacteriology</subject><subject>Biofilms</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>Bithionol</subject><subject>Chromatography, Liquid</subject><subject>Clinical isolates</subject><subject>DNA probes</subject><subject>DNA topoisomerase</subject><subject>Humans</subject><subject>Hydrogen bonding</subject><subject>Hydrogen bonds</subject><subject>Immunoprecipitation</subject><subject>Life Sciences</subject><subject>Medicinal Chemistry</subject><subject>Methicillin-Resistant Staphylococcus aureus</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Organic Chemistry</subject><subject>Peptides</subject><subject>Probes</subject><subject>Proteins</subject><subject>Staphylococcal Infections - microbiology</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - genetics</subject><subject>Tandem Mass Spectrometry</subject><subject>Translocase</subject><subject>tRNA Ala</subject><issn>0021-8820</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kU2LFDEQhoMo7rj6BzxIwIsHo_nq7sTbuvgFCx5cz6E6ncxk6UnaJA07N3-60V4VPHiqFPXUW4EHoaeMvmJUqNdFMsk1oVwQSnumyO09tGNKMcJkr--jHaWcEaU4PUOPSrmhVAxiUA_RmRiY6jrFd-j79cHhJVUXa4AZV8h7V3HyeAz1EFJMM4Y9hFgq_lJhOZzmZJO1a8GwZreWN3hyJezjS1xOsR7au03ihGFZ5mChtogtLdUQTzNUN-Elp9EV_DYkcsEfowce5uKe3NVz9PX9u-vLj-Tq84dPlxdXxAqtK_FCCT2MegQrvZ2AM-Cil6C0BzZYN_Z69N3UOuWtptNIKeso9NY7KagQ4hy92HLb9W-rK9UcQ7FuniG6tBbDFZMdl0Lqhj7_B71Ja47td43iumdSy75RfKNsTqVk582SwxHyyTBqfvoxmx_T_JhffsxtW3p2F72ORzf9WfktpAFiA0obxb3Lf2__J_YH_yueNQ</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Luo, Yue</creator><creator>Wen, Zewen</creator><creator>Xiong, Yanpeng</creator><creator>Chen, Xuecheng</creator><creator>Shen, Zonglin</creator><creator>Li, Peiyu</creator><creator>Peng, Yalan</creator><creator>Deng, Qiwen</creator><creator>Yu, Zhijian</creator><creator>Zheng, Jinxin</creator><creator>Han, Shiqing</creator><general>Springer Japan</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4064-2430</orcidid></search><sort><creationdate>20230701</creationdate><title>The potential target of bithionol against Staphylococcus aureus: design, synthesis and application of biotinylated probes Bio-A2</title><author>Luo, Yue ; Wen, Zewen ; Xiong, Yanpeng ; Chen, Xuecheng ; Shen, Zonglin ; Li, Peiyu ; Peng, Yalan ; Deng, Qiwen ; Yu, Zhijian ; Zheng, Jinxin ; Han, Shiqing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>631/326/22/1290</topic><topic>631/92/609</topic><topic>692/699/255/1318</topic><topic>82</topic><topic>82/58</topic><topic>Alanine</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibacterial activity</topic><topic>Bacteriology</topic><topic>Biofilms</topic><topic>Biomedical and Life Sciences</topic><topic>Bioorganic Chemistry</topic><topic>Bithionol</topic><topic>Chromatography, Liquid</topic><topic>Clinical isolates</topic><topic>DNA probes</topic><topic>DNA topoisomerase</topic><topic>Humans</topic><topic>Hydrogen bonding</topic><topic>Hydrogen bonds</topic><topic>Immunoprecipitation</topic><topic>Life Sciences</topic><topic>Medicinal Chemistry</topic><topic>Methicillin-Resistant Staphylococcus aureus</topic><topic>Microbial Sensitivity Tests</topic><topic>Microbiology</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Organic Chemistry</topic><topic>Peptides</topic><topic>Probes</topic><topic>Proteins</topic><topic>Staphylococcal Infections - microbiology</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - genetics</topic><topic>Tandem Mass Spectrometry</topic><topic>Translocase</topic><topic>tRNA Ala</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Yue</creatorcontrib><creatorcontrib>Wen, Zewen</creatorcontrib><creatorcontrib>Xiong, Yanpeng</creatorcontrib><creatorcontrib>Chen, Xuecheng</creatorcontrib><creatorcontrib>Shen, Zonglin</creatorcontrib><creatorcontrib>Li, Peiyu</creatorcontrib><creatorcontrib>Peng, Yalan</creatorcontrib><creatorcontrib>Deng, Qiwen</creatorcontrib><creatorcontrib>Yu, Zhijian</creatorcontrib><creatorcontrib>Zheng, Jinxin</creatorcontrib><creatorcontrib>Han, Shiqing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>ProQuest Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Yue</au><au>Wen, Zewen</au><au>Xiong, Yanpeng</au><au>Chen, Xuecheng</au><au>Shen, Zonglin</au><au>Li, Peiyu</au><au>Peng, Yalan</au><au>Deng, Qiwen</au><au>Yu, Zhijian</au><au>Zheng, Jinxin</au><au>Han, Shiqing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The potential target of bithionol against Staphylococcus aureus: design, synthesis and application of biotinylated probes Bio-A2</atitle><jtitle>Journal of antibiotics</jtitle><stitle>J Antibiot</stitle><addtitle>J Antibiot (Tokyo)</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>76</volume><issue>7</issue><spage>406</spage><epage>415</epage><pages>406-415</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><abstract>This study aims to explore the potential targets of bithionol in Staphylococcus aureus .The four bithionol biotinylated probes Bio-A2-1 , Bio-A2-2 , Bio-A2-3 , and Bio-A2-4 were synthesized, the minimal inhibitory concentrations (MICs) of these probes against S. aureus were determined. The bithionol binding proteins in S. aureus were identified through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe. The biotinylated bithionol probes Bio-A2-1 and Bio-A2-3 displayed antibacterial activities against S. aureus . The Bio-A2-1 showed lower MICs than Bio-A2-3 , and both with the MIC 50 /MIC 90 at 12.5/12.5 μM against S. aureus clinical isolates. The inhibition rates of bithionol biotinylated probes Bio-A2-1 and Bio-A2-3 on the biofilm formation of S. aureus were comparable to that of bithionol, and were stronger than that of Bio-A2-2 and Bio-A2-4 . The biofilm formation of 10 out of 12 S. aureus clinical isolates could be inhibited by Bio-A2-1 (at 1/4×, or 1/2× MICs). There are three proteins identified in S. aureus through immunoprecipitation and LC-MS/MS with bithionol biotinylated probe Bio-A2-1 : Protein translocase subunit SecA 1 ( secA1 ), Alanine--tRNA ligase ( alaS ) and DNA gyrase subunit A ( gyrA ), and in which the SecA1 protein the highest coverage and the most unique peptides. The LYS112, GLN143, ASP213, GLY496 and ASP498 of SecA1 protein act as hydrogen acceptors to form 6 hydrogen bonds with bithionol biotinylated probe Bio-A2-1 by molecular docking analysis. In conclusion, the bithionol biotinylated probe Bio-A2-1 has antibacterial and anti-biofilm activities against S. aureus , and SecA1 was probably one of the potential targets of bithionol in S. aureus .</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>37185582</pmid><doi>10.1038/s41429-023-00618-x</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-4064-2430</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0021-8820
ispartof Journal of antibiotics, 2023-07, Vol.76 (7), p.406-415
issn 0021-8820
1881-1469
language eng
recordid cdi_proquest_miscellaneous_2814524349
source Springer Link
subjects 631/326/22/1290
631/92/609
692/699/255/1318
82
82/58
Alanine
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibacterial activity
Bacteriology
Biofilms
Biomedical and Life Sciences
Bioorganic Chemistry
Bithionol
Chromatography, Liquid
Clinical isolates
DNA probes
DNA topoisomerase
Humans
Hydrogen bonding
Hydrogen bonds
Immunoprecipitation
Life Sciences
Medicinal Chemistry
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Microbiology
Molecular docking
Molecular Docking Simulation
Organic Chemistry
Peptides
Probes
Proteins
Staphylococcal Infections - microbiology
Staphylococcus aureus
Staphylococcus aureus - genetics
Tandem Mass Spectrometry
Translocase
tRNA Ala
title The potential target of bithionol against Staphylococcus aureus: design, synthesis and application of biotinylated probes Bio-A2
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T20%3A27%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20potential%20target%20of%20bithionol%20against%20Staphylococcus%20aureus:%20design,%20synthesis%20and%20application%20of%20biotinylated%20probes%20Bio-A2&rft.jtitle=Journal%20of%20antibiotics&rft.au=Luo,%20Yue&rft.date=2023-07-01&rft.volume=76&rft.issue=7&rft.spage=406&rft.epage=415&rft.pages=406-415&rft.issn=0021-8820&rft.eissn=1881-1469&rft_id=info:doi/10.1038/s41429-023-00618-x&rft_dat=%3Cproquest_cross%3E2814524349%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c399t-f38397b9bac4fcda21a2364a89fa17ceb69bf5d9fa8fc90db00150a6cfe430333%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2829614946&rft_id=info:pmid/37185582&rfr_iscdi=true