ArticleNature communications2021
Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07018076 (Candidate Clinical Correlate of Prognostic Outcome for TB Study), which is not on this map. Cited by 72 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 5% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Candidate Clinical Correlate of Prognostic Outcome for TB Study
Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Effects of Respiratory Isolation for Tuberculosis to Reduce Community-based Transmission: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Pooled it
- A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.The Journal of antimicrobial chemotherapy · 2024Trial
- Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model.ImmunoHorizons · 2024Trial
- Direct bacterial transcript visualization illuminates spatiotemporal environmental adaptation ofScience advances · 2026Article
- Immortal genome assumption significantly underestimates replication and death rates ofMicrobiology spectrum · 2026Article
- Mtb-Timer: a fluorescent reporter to visualizemSystems · 2026Article
- Infection dose shapes granuloma phenotypes in a humanized mouse model of tuberculosis.Research square · 2026Article
- Pretomanid vs delamanid in a bedaquiline-linezolid regimen: efficacy in a high-burden tuberculosis mouse model.Antimicrobial agents and chemotherapy · 2026Article
- Immortal genome assumption significantly underestimates replication and death rates ofbioRxiv : the preprint server for biology · 2026Article
- Future Prospects for Using Clinical Phenotypes in Tuberculosis Precision Medicine-An Approach for Clinical Management.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Review
- The ribosomal RNA synthesis ratio biomarker in Mycobacterium ulcerans for drug activity evaluation.Infectious diseases of poverty · 2026Article
- Identification and characterization of inhibitors of the tuberculosis phosphatase PstP.The Journal of biological chemistry · 2026Article
- Physiologic recovery of Mycobacterium tuberculosis from drug injury: A molecular study of post antibiotic effect in vitro and in vivo.PLoS pathogens · 2026Article
- Adaptive immunity shapes baseline physiology ofbioRxiv : the preprint server for biology · 2026Article
- Type I interferons in tuberculosis pathogenesis and prevention.Trends in microbiology · 2026Review
- A modeling-based framework to evaluate forgiveness of tuberculosis treatment in a BALB/c relapsing mouse model.Antimicrobial agents and chemotherapy · 2026Article
- Simultaneous measurement of 16S-rRNA and pre-16S-rRNA as a strategy to monitor clinical tuberculosis.Frontiers in antibiotics · 2026Article
- Same class, different activity: Delamanid and pretomanid have comparable bactericidal activity but pretomanid potently inhibitsbioRxiv : the preprint server for biology · 2025Article
- Novel molecular assessment method using precursor ribosomal RNA to rapidly quantify hard-to-monitor pathogens in aqueous suspensions: application to ultraviolet disinfection ofJournal of water and health · 2025Article
- Phase 2C clinical trial of novel short-course regimens for the treatment of pulmonary tuberculosis: TBTC study 38/CRUSH-TB design.Contemporary clinical trials · 2025Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
41 authors at 16 institutions in 8 countries.
Nicholas D Walter *Rocky Mountain Regional VA Medical Center, Aurora, CO, USA. nicholas.walter@cuanschutz.edu.ORCID 0000-0003-0126-1993
Sarah E M Born *Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0001-5964-3121
Gregory T Robertson *Consortium for Applied Microbial Metrics, Aurora, CO, USA.
Matthew ReichlenDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Christian Dide-AgossouDepartment of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Victoria A EktnitphongMycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
Karen RossmasslerRocky Mountain Regional VA Medical Center, Aurora, CO, USA.
Michelle E RameyMycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
Allison A BaumanMycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
Victor OzolsRocky Mountain Regional VA Medical Center, Aurora, CO, USA.
Shelby C BearrowsRocky Mountain Regional VA Medical Center, Aurora, CO, USA.
Gary SchoolnikDivision of Infectious Diseases and Geographic Medicine, Stanford University, Palo Alto, CA, USA.
Gregory DolganovDivision of Infectious Diseases and Geographic Medicine, Stanford University, Palo Alto, CA, USA.
Benjamin GarciaIntegrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.ORCID 0000-0001-5524-6946
Emmanuel MusisiInfectious Disease Research Collaboration, Kampala, Uganda.
William WorodriaInfectious Disease Research Collaboration, Kampala, Uganda.
Laurence HuangDivision of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA.
J Lucian DavisDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.ORCID 0000-0002-8629-9992
Nhung V NguyenVietnam National TB Programme/UCSF Research Collaboration Unit, Hanoi, Vietnam.
Hung V NguyenVietnam National TB Programme/UCSF Research Collaboration Unit, Hanoi, Vietnam.
Anh T V NguyenVietnam National TB Programme/UCSF Research Collaboration Unit, Hanoi, Vietnam.
Ha PhanVietnam National TB Programme/UCSF Research Collaboration Unit, Hanoi, Vietnam.
Carol WiluszMycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
Brendan K PodellMycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
N' Dira SanoussiLaboratoire de Référence des Mycobactéries, Cotonou, Benin.ORCID 0000-0002-0516-574X
Bouke C de JongMycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.ORCID 0000-0002-1017-4675
Corinne S MerleLondon School of Hygiene and Tropical Medicine, London, UK.
Dissou AffolabiLaboratoire de Référence des Mycobactéries, Cotonou, Benin.
Helen McIlleronDivision of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
Maria Garcia-CremadesDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-3369-1210
Ekaterina MaidjiDivision of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Franceen Eshun-WilsonDivision of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Brandon Aguilar-RodriguezDivision of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Dhuvarakesh KarthikeyanDivision of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Khisimuzi MdluliBill & Melinda Gates Medical Research Institute, Cambridge, MA, USA.
Cathy BansbachBill and Melinda Gates Foundation, Seattle, WA, USA.
Anne J LenaertsMycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
Radojka M SavicConsortium for Applied Microbial Metrics, Aurora, CO, USA.ORCID 0000-0003-3143-5579
Payam NahidConsortium for Applied Microbial Metrics, Aurora, CO, USA.
Joshua J VásquezConsortium for Applied Microbial Metrics, Aurora, CO, USA.ORCID 0000-0002-7165-5739
Martin I VoskuilConsortium for Applied Microbial Metrics, Aurora, CO, USA. martin.voskuil@cuanschutz.edu.ORCID 0000-0002-9565-7923
Colorado State University · USUniversity of California, San Francisco · USUniversity of Colorado Anschutz Medical Campus · USVietnam National University, Hanoi · VNSan Francisco General Hospital · USAidjan-Lagos Corridor Organization · BJGates Foundation · USInfectious Diseases Research Collaboration · UGProtein Metrics (United States) · USStanford University · USColorado School of Public Health · USInstituut voor Tropische Geneeskunde · BELondon School of Hygiene & Tropical Medicine · GBNational Jewish Health · USUniversity of Cape Town · ZAYale University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MVirology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6MInflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study - Diversity SupplementR01HL128156 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE, HUNT, PETER W · 2015 to 2024
$7.1MSputum Transcriptomic Expression Profiling in Study 31: Express 31R01AI127300 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DAVIS, JOHN LUCIAN, NAHID, PAYAM · 2017 to 2022
$6.2MInternational HIV-associated Opportunistic Pneumonias (IHOP) StudyR01HL090335 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE · 2007 to 2011
$4.0MIdentifying Optimal Treatment Strategies for Tuberculosis TreatmentR01AI135124 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALLAND, DAVID, SAVIC, RADOJKA · 2019 to 2023
$3.8MTB and Other Pulmonary Complications of AIDS Research Training ProgramD43TW009607 · FIC · YALE UNIVERSITY · PI DAVIS, JOHN LUCIAN, KATAMBA, ACHILLES · 2013 to 2022
$3.2MIntegrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) StudyR01HL143998 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTENSON, STEPHANIE A, HUANG, LAURENCE · 2019 to 2022
$3.2MPatient-Oriented Research and Mentoring in PneumocystisK24HL087713 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE · 2006 to 2018
$1.8MThe impact of the HIV reservoir on pulmonary myeloid cells: virology, phenotype, and functionK01HL140804 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VASQUEZ, JOSHUA · 2019 to 2023
$956kThe impact of TB co-infection on the reservoir of persistent HIV in vivoR21AI116295 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUNT, PETER W · 2015 to 2016
$436kPrecursor-rRNA profiling as a measure of drug activity in tuberculosisR21AI135652 · NIAID · UNIVERSITY OF COLORADO DENVER · PI VOSKUIL, MARTIN INUA, WALTER, NICHOLAS D · 2018 to 2019
$435kBLRD VA I01 BX004527CSRD VA IK2 CX000914FIC NIH HHS D43 TW009607NHLBI NIH HHS K01 HL140804NHLBI NIH HHS K24 HL087713NHLBI NIH HHS R01 HL090335NHLBI NIH HHS R01 HL128156NHLBI NIH HHS R01 HL143998NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI127300NIAID NIH HHS R01 AI135124NIAID NIH HHS R21 AI101714NIAID NIH HHS R21 AI116295NIAID NIH HHS R21 AI135652Wellcome TrustWellcome Trust 206379/Z/17/ZWorld Health Organization 001
Abstract
There is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and regimens vary in treatment-shortening activity, but the molecular basis of these differences is unclear, and no existing assay directly quantifies the ability of a drug or regimen to shorten treatment. Here, we show that drugs historically classified as sterilizing and non-sterilizing have distinct impacts on a fundamental aspect of Mycobacterium tuberculosis physiology: ribosomal RNA (rRNA) synthesis. In culture, in mice, and in human studies, measurement of precursor rRNA reveals that sterilizing drugs and highly effective drug regimens profoundly suppress M. tuberculosis rRNA synthesis, whereas non-sterilizing drugs and weaker regimens do not. The rRNA synthesis ratio provides a readout of drug effect that is orthogonal to traditional measures of bacterial burden. We propose that this metric of drug activity may accelerate the development of shorter TB regimens.
Indexed as
AnimalsAntitubercular AgentsDisease Models, AnimalFemaleHumansMiceMice, Inbred BALB CMycobacterium tuberculosisRNA, BacterialRNA PrecursorsRNA, RibosomalTreatment OutcomeTuberculosisAntitubercular AgentsRNA, BacterialRNA PrecursorsRNA, Ribosomal
Identifiers
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LicenceCC BY
Read underepoch 390
Registered trials
NCT07018076ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.