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Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden
There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay cal...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557932/ https://www.ncbi.nlm.nih.gov/pubmed/34494858 http://dx.doi.org/10.1128/Spectrum.00481-21 |
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author | Musisi, Emmanuel Dide-Agossou, Christian Al Mubarak, Reem Rossmassler, Karen Ssesolo, Abdul Wahab Kaswabuli, Sylvia Byanyima, Patrick Sanyu, Ingvar Zawedde, Josephine Worodria, William Voskuil, Martin I. Savic, Rada M. Nahid, Payam Davis, J. Lucian Huang, Laurence Moore, Camille M. Walter, Nicholas D. |
author_facet | Musisi, Emmanuel Dide-Agossou, Christian Al Mubarak, Reem Rossmassler, Karen Ssesolo, Abdul Wahab Kaswabuli, Sylvia Byanyima, Patrick Sanyu, Ingvar Zawedde, Josephine Worodria, William Voskuil, Martin I. Savic, Rada M. Nahid, Payam Davis, J. Lucian Huang, Laurence Moore, Camille M. Walter, Nicholas D. |
author_sort | Musisi, Emmanuel |
collection | PubMed |
description | There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. IMPORTANCE This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. |
format | Online Article Text |
id | pubmed-8557932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-85579322021-11-08 Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden Musisi, Emmanuel Dide-Agossou, Christian Al Mubarak, Reem Rossmassler, Karen Ssesolo, Abdul Wahab Kaswabuli, Sylvia Byanyima, Patrick Sanyu, Ingvar Zawedde, Josephine Worodria, William Voskuil, Martin I. Savic, Rada M. Nahid, Payam Davis, J. Lucian Huang, Laurence Moore, Camille M. Walter, Nicholas D. Microbiol Spectr Research Article There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. IMPORTANCE This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. American Society for Microbiology 2021-09-08 /pmc/articles/PMC8557932/ /pubmed/34494858 http://dx.doi.org/10.1128/Spectrum.00481-21 Text en Copyright © 2021 Musisi et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Musisi, Emmanuel Dide-Agossou, Christian Al Mubarak, Reem Rossmassler, Karen Ssesolo, Abdul Wahab Kaswabuli, Sylvia Byanyima, Patrick Sanyu, Ingvar Zawedde, Josephine Worodria, William Voskuil, Martin I. Savic, Rada M. Nahid, Payam Davis, J. Lucian Huang, Laurence Moore, Camille M. Walter, Nicholas D. Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden |
title | Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden |
title_full | Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden |
title_fullStr | Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden |
title_full_unstemmed | Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden |
title_short | Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden |
title_sort | reproducibility of the ribosomal rna synthesis ratio in sputum and association with markers of mycobacterium tuberculosis burden |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557932/ https://www.ncbi.nlm.nih.gov/pubmed/34494858 http://dx.doi.org/10.1128/Spectrum.00481-21 |
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