Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development
Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of vaccines and drugs in animal models and human...
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| Veröffentlicht in: | Diagnostic microbiology and infectious disease 2024-01, Vol.108 (1), p.116106, Article 116106 |
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| creator | Chang, Ming Venkatasubramanian, Sambasivan Barrett, Holly Urdahl, Kevin B Weigel, Kris M Cangelosi, Gerard A Shah, Javeed A Saha, Aparajita Feng, Libing Adams, Kristin N Sherman, David R Smith, Nahum Seshadri, Chetan Kublin, James G Murphy, Sean C |
| description | Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of vaccines and drugs in animal models and human clinical trials. Here, a real-time reverse transcription PCR (RT-PCR) assay was developed to detect pre-ribosomal RNA (pre-rRNA) of Mycobacterium bovis bacille Calmette-Guérin (BCG) and Mtb. This pre-rRNA biomarker is indicative of bacterial viability. In two different mouse models, the presence of pre-rRNA from BCG and Mtb in ex vivo tissues showed excellent agreement with slower culture-based colony-forming unit assays. The addition of a brief nutritional stimulation prior to molecular viability testing further differentiated viable but dormant mycobacteria from dead mycobacteria. This research has set the stage to evaluate pre-rRNA as a BCG and/or Mtb infection biomarker in future drug and vaccine clinical studies. |
| doi_str_mv | 10.1016/j.diagmicrobio.2023.116106 |
| format | Article |
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Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of vaccines and drugs in animal models and human clinical trials. Here, a real-time reverse transcription PCR (RT-PCR) assay was developed to detect pre-ribosomal RNA (pre-rRNA) of Mycobacterium bovis bacille Calmette-Guérin (BCG) and Mtb. This pre-rRNA biomarker is indicative of bacterial viability. In two different mouse models, the presence of pre-rRNA from BCG and Mtb in ex vivo tissues showed excellent agreement with slower culture-based colony-forming unit assays. The addition of a brief nutritional stimulation prior to molecular viability testing further differentiated viable but dormant mycobacteria from dead mycobacteria. This research has set the stage to evaluate pre-rRNA as a BCG and/or Mtb infection biomarker in future drug and vaccine clinical studies.</description><identifier>ISSN: 0732-8893</identifier><identifier>ISSN: 1879-0070</identifier><identifier>EISSN: 1879-0070</identifier><identifier>DOI: 10.1016/j.diagmicrobio.2023.116106</identifier><identifier>PMID: 37931386</identifier><language>eng</language><publisher>United States: Elsevier Biomedical</publisher><subject>Animals ; BCG Vaccine ; Biomarkers ; Humans ; Mice ; Mycobacterium bovis - genetics ; Mycobacterium tuberculosis - genetics ; Original ; RNA Precursors ; Tuberculosis - diagnosis ; Tuberculosis - prevention & control ; Vaccine Development</subject><ispartof>Diagnostic microbiology and infectious disease, 2024-01, Vol.108 (1), p.116106, Article 116106</ispartof><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2023 The Authors 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-b21f8f0484c66c7569cf2ec2aef49d2832a3a6ccdcf20cbecf75d68302634c333</citedby><cites>FETCH-LOGICAL-c427t-b21f8f0484c66c7569cf2ec2aef49d2832a3a6ccdcf20cbecf75d68302634c333</cites><orcidid>0000-0002-7832-4270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37931386$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Ming</creatorcontrib><creatorcontrib>Venkatasubramanian, Sambasivan</creatorcontrib><creatorcontrib>Barrett, Holly</creatorcontrib><creatorcontrib>Urdahl, Kevin B</creatorcontrib><creatorcontrib>Weigel, Kris M</creatorcontrib><creatorcontrib>Cangelosi, Gerard A</creatorcontrib><creatorcontrib>Shah, Javeed A</creatorcontrib><creatorcontrib>Saha, Aparajita</creatorcontrib><creatorcontrib>Feng, Libing</creatorcontrib><creatorcontrib>Adams, Kristin N</creatorcontrib><creatorcontrib>Sherman, David R</creatorcontrib><creatorcontrib>Smith, Nahum</creatorcontrib><creatorcontrib>Seshadri, Chetan</creatorcontrib><creatorcontrib>Kublin, James G</creatorcontrib><creatorcontrib>Murphy, Sean C</creatorcontrib><title>Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development</title><title>Diagnostic microbiology and infectious disease</title><addtitle>Diagn Microbiol Infect Dis</addtitle><description>Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. 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This research has set the stage to evaluate pre-rRNA as a BCG and/or Mtb infection biomarker in future drug and vaccine clinical studies.</description><subject>Animals</subject><subject>BCG Vaccine</subject><subject>Biomarkers</subject><subject>Humans</subject><subject>Mice</subject><subject>Mycobacterium bovis - genetics</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Original</subject><subject>RNA Precursors</subject><subject>Tuberculosis - diagnosis</subject><subject>Tuberculosis - prevention & control</subject><subject>Vaccine Development</subject><issn>0732-8893</issn><issn>1879-0070</issn><issn>1879-0070</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1u1DAQxy0EokvhFVDEiUsWf2RthwuqVqUgtSAhOFvOZLL1yrEXO1mpj8QrcOXF8HZL1XKyPPP_GOlHyBtGl4wy-W677J3djA5S7FxccsrFkjHJqHxCFkyrtqZU0adkQZXgtdatOCEvct5Synjb0OfkRKhWMKHlgvy-ih5h9jZVPU4Ik4uhikO1S1gn18UcR-urb1_O8mF6dQOxszBhcvNYdXHvclX-znus1taPOE1YX8x_fiUXKhv6_wzT3GEqZTEX3xQrDNc2AN6WgXfBQel6JOrTvLkN2lsAF7AcuUcfdyOG6SV5Nlif8dXde0p-fDz_vv5UX369-Lw-u6yh4WqqO84GPdBGNyAlqJVsYeAI3OLQtD3XglthJUBfxhQ6hEGteqkF5VI0IIQ4JR-Oubu5G7GHUp2sN7vkRptuTLTOPN4Ed202cW8YVbylq0PC27uEFH_OmCczugzovQ0Y52y41rIVSildpO-P0gI354TDfQ-j5kDfbM1D-uZA3xzpF_Prh5feW__hFn8BCvi4JQ</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Chang, Ming</creator><creator>Venkatasubramanian, Sambasivan</creator><creator>Barrett, Holly</creator><creator>Urdahl, Kevin B</creator><creator>Weigel, Kris M</creator><creator>Cangelosi, Gerard A</creator><creator>Shah, Javeed A</creator><creator>Saha, Aparajita</creator><creator>Feng, Libing</creator><creator>Adams, Kristin N</creator><creator>Sherman, David R</creator><creator>Smith, Nahum</creator><creator>Seshadri, Chetan</creator><creator>Kublin, James G</creator><creator>Murphy, Sean C</creator><general>Elsevier Biomedical</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>5PM</scope><orcidid>https://orcid.org/0000-0002-7832-4270</orcidid></search><sort><creationdate>202401</creationdate><title>Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development</title><author>Chang, Ming ; Venkatasubramanian, Sambasivan ; Barrett, Holly ; Urdahl, Kevin B ; Weigel, Kris M ; Cangelosi, Gerard A ; Shah, Javeed A ; Saha, Aparajita ; Feng, Libing ; Adams, Kristin N ; Sherman, David R ; Smith, Nahum ; Seshadri, Chetan ; Kublin, James G ; Murphy, Sean C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-b21f8f0484c66c7569cf2ec2aef49d2832a3a6ccdcf20cbecf75d68302634c333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>BCG Vaccine</topic><topic>Biomarkers</topic><topic>Humans</topic><topic>Mice</topic><topic>Mycobacterium bovis - genetics</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Original</topic><topic>RNA Precursors</topic><topic>Tuberculosis - diagnosis</topic><topic>Tuberculosis - prevention & control</topic><topic>Vaccine Development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Ming</creatorcontrib><creatorcontrib>Venkatasubramanian, Sambasivan</creatorcontrib><creatorcontrib>Barrett, Holly</creatorcontrib><creatorcontrib>Urdahl, Kevin B</creatorcontrib><creatorcontrib>Weigel, Kris M</creatorcontrib><creatorcontrib>Cangelosi, Gerard A</creatorcontrib><creatorcontrib>Shah, Javeed A</creatorcontrib><creatorcontrib>Saha, Aparajita</creatorcontrib><creatorcontrib>Feng, Libing</creatorcontrib><creatorcontrib>Adams, Kristin N</creatorcontrib><creatorcontrib>Sherman, David R</creatorcontrib><creatorcontrib>Smith, Nahum</creatorcontrib><creatorcontrib>Seshadri, Chetan</creatorcontrib><creatorcontrib>Kublin, James G</creatorcontrib><creatorcontrib>Murphy, Sean C</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>PubMed Central (Full Participant titles)</collection><jtitle>Diagnostic microbiology and infectious disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Ming</au><au>Venkatasubramanian, Sambasivan</au><au>Barrett, Holly</au><au>Urdahl, Kevin B</au><au>Weigel, Kris M</au><au>Cangelosi, Gerard A</au><au>Shah, Javeed A</au><au>Saha, Aparajita</au><au>Feng, Libing</au><au>Adams, Kristin N</au><au>Sherman, David R</au><au>Smith, Nahum</au><au>Seshadri, Chetan</au><au>Kublin, James G</au><au>Murphy, Sean C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development</atitle><jtitle>Diagnostic microbiology and infectious disease</jtitle><addtitle>Diagn Microbiol Infect Dis</addtitle><date>2024-01</date><risdate>2024</risdate><volume>108</volume><issue>1</issue><spage>116106</spage><pages>116106-</pages><artnum>116106</artnum><issn>0732-8893</issn><issn>1879-0070</issn><eissn>1879-0070</eissn><abstract>Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. 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| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals BCG Vaccine Biomarkers Humans Mice Mycobacterium bovis - genetics Mycobacterium tuberculosis - genetics Original RNA Precursors Tuberculosis - diagnosis Tuberculosis - prevention & control Vaccine Development |
| title | Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development |
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