Advances in the development of new tuberculosis drugs and treatment regimens.

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🔗 View Article (PMID 23629506)

Published in Nat Rev Drug Discov on May 01, 2013

Authors

Alimuddin Zumla1, Payam Nahid, Stewart T Cole

Author Affiliations

1: Center for Clinical Microbiology, Division of Infection and Immunity, University College London Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.

Associated clinical trials:

Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis (REMoxTB) | NCT00864383

A Placebo-controlled, Phase 2 Trial to Evaluate OPC 67683 in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB) | NCT00685360

Safety and Efficacy Trial of Delamanid for 6 Months in Patients With Multidrug Resistant Tuberculosis | NCT01424670

TBTC Study 29: Rifapentine During Intensive Phase Tuberculosis (TB) Treatment | NCT00694629

A Controlled Trial of a 4-Month Quinolone-Containing Regimen for the Treatment of Pulmonary Tuberculosis | NCT00216385

Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) (NC-003) | NCT01691534

REMEMBER: Reducing Early Mortality & Morbidity by Empiric Tuberculosis (TB) Treatment (REMEMBER) | NCT01380080

Evaluation of 8 Weeks of Treatment With the Combination of Moxifloxacin, PA-824 and Pyrazinamide in Patients With Drug Sensitive and Multi Drug-Resistant Pulmonary Tuberculosis (TB) (NC-002) | NCT01498419

Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis (High RIF) | NCT00760149

Trial of High-Dose Rifampin in Patients With TB (HIRIF) | NCT01408914

Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis | NCT00728507

Safety, Tolerability, Pharmacokinetics And Measurement Of Whole Blood Activity (WBA) Of PNU-100480 After Multiple Oral Doses In Healthy Adult Volunteers | NCT00990990

Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB (SQ109EBA) | NCT01218217

Study of Daily Rifapentine for Pulmonary Tuberculosis | NCT00814671

Safety, Tolerability, Extended Early Bactericidal Activity and PK of Higher Doses Rifampicin in Adults With Pulmonary TB (HR1) | NCT01392911

Phase 2a EBA Trial of AZD5847 | NCT01516203

Evaluation of SQ109, High-dose Rifampicin, and Moxifloxacin in Adults With Smear-positive Pulmonary TB in a MAMS Design | NCT01785186

PNU-100480 In Newly Diagnosed, Drug Sensitive Patients With Pulmonary TB; Early Bactericidal Activity; Whole Blood Assay | NCT01225640

Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment (PrOMPT) | NCT01417988

Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis | NCT01131351

Evaluating the Pharmacokinetics of High-Dose Rifapentine When Given as a Single Dose or in Divided Doses to Healthy Adults | NCT01574638

TMC207 +/- Rifabutin/Rifampin | NCT01341184

Essentiality of INH in TB Therapy | NCT01589497

Evaluating the Safety and Drug Interaction of PA-824, an Investigational Tuberculosis Medication, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin | NCT01571414

Effect of PA-824 and of PA-824 Plus Moxifloxacin on the QTc Interval in Healthy Volunteers | NCT01674218

Pilot Clinical Trial of PRS TB Regimen I - Phase II | NCT03561753

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Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect Immun (2006) 2.56

Macro-array and bioinformatic analyses reveal mycobacterial 'core' genes, variation in the ESAT-6 gene family and new phylogenetic markers for the Mycobacterium tuberculosis complex. Microbiology (2004) 2.40

Effect of katG mutations on the virulence of Mycobacterium tuberculosis and the implication for transmission in humans. Infect Immun (2002) 2.35

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Drug-resistant tuberculosis: time for visionary political leadership. Lancet Infect Dis (2013) 2.16

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Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog (2009) 1.96

Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP. PLoS Pathog (2008) 1.94

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Genome-wide comparison of medieval and modern Mycobacterium leprae. Science (2013) 1.81

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Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis. Sci Transl Med (2012) 1.78

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Reaching the limits of tuberculosis prevention among foreign-born individuals: a tuberculosis-control program perspective. Clin Infect Dis (2008) 1.74

Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis. Tuberculosis (Edinb) (2005) 1.73

PknB kinase activity is regulated by phosphorylation in two Thr residues and dephosphorylation by PstP, the cognate phospho-Ser/Thr phosphatase, in Mycobacterium tuberculosis. Mol Microbiol (2003) 1.69

Functional analysis of early secreted antigenic target-6, the dominant T-cell antigen of Mycobacterium tuberculosis, reveals key residues involved in secretion, complex formation, virulence, and immunogenicity. J Biol Chem (2005) 1.64

Genotypic analysis of Mycobacterium tuberculosis in Bangladesh and prevalence of the Beijing strain. J Clin Microbiol (2004) 1.63

Influence of ESAT-6 secretion system 1 (RD1) of Mycobacterium tuberculosis on the interaction between mycobacteria and the host immune system. J Immunol (2005) 1.61

Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone. Cell Microbiol (2005) 1.56

Common evolutionary origin for the unstable virulence plasmid pMUM found in geographically diverse strains of Mycobacterium ulcerans. J Bacteriol (2005) 1.55

Bacterial artificial chromosome-based comparative genomic analysis identifies Mycobacterium microti as a natural ESAT-6 deletion mutant. Infect Immun (2002) 1.54

Isolation of three Mycobacterium ulcerans strains resistant to rifampin after experimental chemotherapy of mice. Antimicrob Agents Chemother (2003) 1.54

Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium. J Infect Dis (2012) 1.53

An increase in antimycobacterial Th1-cell responses by prime-boost protocols of immunization does not enhance protection against tuberculosis. Infect Immun (2006) 1.51

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Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. J Exp Med (2007) 1.48

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Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva. PLoS Med (2007) 1.47

Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother (2010) 1.43

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Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans. Microbiology (2005) 1.38

A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra. J Bacteriol (2007) 1.38

Characterization of active site structure in CYP121. A cytochrome P450 essential for viability of Mycobacterium tuberculosis H37Rv. J Biol Chem (2008) 1.37

Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis. Antimicrob Agents Chemother (2014) 1.36

Towards a new tuberculosis drug: pyridomycin - nature's isoniazid. EMBO Mol Med (2012) 1.36

Benzothiazinones: prodrugs that covalently modify the decaprenylphosphoryl-β-D-ribose 2'-epimerase DprE1 of Mycobacterium tuberculosis. J Am Chem Soc (2010) 1.35

Benzothiazinones are suicide inhibitors of mycobacterial decaprenylphosphoryl-β-D-ribofuranose 2'-oxidase DprE1. J Am Chem Soc (2011) 1.33

Identification using LC-MSn of co-metabolites in the biosynthesis of the polyketide toxin mycolactone by a clinical isolate of Mycobacterium ulcerans. Chem Commun (Camb) (2003) 1.33

Streptomycin-starved Mycobacterium tuberculosis 18b, a drug discovery tool for latent tuberculosis. Antimicrob Agents Chemother (2012) 1.31

Cell envelope protein PPE68 contributes to Mycobacterium tuberculosis RD1 immunogenicity independently of a 10-kilodalton culture filtrate protein and ESAT-6. Infect Immun (2004) 1.31

Diversity-oriented synthesis of furo[3,2-f]chromanes with antimycobacterial activity. Eur J Med Chem (2009) 1.29

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Leads for antitubercular compounds from kinase inhibitor library screens. Tuberculosis (Edinb) (2010) 1.28

Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol Med (2014) 1.27

In vitro combination studies of benzothiazinone lead compound BTZ043 against Mycobacterium tuberculosis. Antimicrob Agents Chemother (2012) 1.27

The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth. J Bacteriol (2006) 1.27

Massively parallel pathogen identification using high-density microarrays. Microb Biotechnol (2008) 1.26

Rising standards for tuberculosis drug development. Trends Pharmacol Sci (2008) 1.25

Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein. PLoS Pathog (2012) 1.25

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Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy. J Immunol (2005) 1.24

Elucidating novel serum biomarkers associated with pulmonary tuberculosis treatment. PLoS One (2013) 1.24

Multitarget drug discovery for tuberculosis and other infectious diseases. J Med Chem (2014) 1.24

Discriminating between latent and active tuberculosis with multiple biomarker responses. Tuberculosis (Edinb) (2011) 1.22

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A comprehensive survey of single nucleotide polymorphisms (SNPs) across Mycobacterium bovis strains and M. bovis BCG vaccine strains refines the genealogy and defines a minimal set of SNPs that separate virulent M. bovis strains and M. bovis BCG strains. Infect Immun (2009) 1.21

Tuberculosis drug discovery in the post-post-genomic era. EMBO Mol Med (2014) 1.20

Structure and mechanism of the alkyl hydroperoxidase AhpC, a key element of the Mycobacterium tuberculosis defense system against oxidative stress. J Biol Chem (2005) 1.19

Inactivation of Rv2525c, a substrate of the twin arginine translocation (Tat) system of Mycobacterium tuberculosis, increases beta-lactam susceptibility and virulence. J Bacteriol (2006) 1.17

Application of broad-spectrum resequencing microarray for genotyping rhabdoviruses. J Virol (2010) 1.16

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Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens. J Infect Dis (2004) 1.13

Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics. Microbiology (2005) 1.13

Mycobacterium leprae: genes, pseudogenes and genetic diversity. Future Microbiol (2011) 1.13

Development of a repressible mycobacterial promoter system based on two transcriptional repressors. Nucleic Acids Res (2010) 1.13

Early trafficking events of Mycobacterium ulcerans within Naucoris cimicoides. Cell Microbiol (2006) 1.12

Antigen discovery: a postgenomic approach to leprosy diagnosis. Infect Immun (2006) 1.12

Biological and structural characterization of the Mycobacterium smegmatis nitroreductase NfnB, and its role in benzothiazinone resistance. Mol Microbiol (2010) 1.12

Towards an immunodiagnostic test for leprosy. Microbes Infect (2006) 1.10

Evaluation of quantitative IFN-gamma response for risk stratification of active tuberculosis suspects. Am J Respir Crit Care Med (2009) 1.09

ESAT-6 secretion-independent impact of ESX-1 genes espF and espG1 on virulence of Mycobacterium tuberculosis. J Infect Dis (2010) 1.09

A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium tuberculosis. Microbiol Res (2007) 1.08

Immunogenicity of Mycobacterium ulcerans Hsp65 and protective efficacy of a Mycobacterium leprae Hsp65-based DNA vaccine against Buruli ulcer. Microbes Infect (2006) 1.06

Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones. Antimicrob Agents Chemother (2010) 1.05

Relapse associated with active disease caused by Beijing strain of Mycobacterium tuberculosis. Emerg Infect Dis (2009) 1.05