ArticlePloS one2012
Resistance to first-line anti-TB drugs is associated with reduced nitric oxide susceptibility in Mycobacterium tuberculosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- CDK1‑induced regulation of p53 phosphorylation at Ser315 mediates cell cycle arrest and apoptosis of macrophages infected with clinical isolates ofMolecular medicine reports · 2026Article
- Nitric oxide brings innate immune resistance toJournal of biosciences · 2024Article
- Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.The Journal of infectious diseases · 2021Article
- Nitric Oxide Does Not Inhibit but Is Metabolized by the CytochromeInternational journal of molecular sciences · 2020Article
- The Association of Tuberculosis Mono-infection and Tuberculosis-Human Immunodeficiency Virus (TB-HIV) Co-infection in the Pathogenesis of Hypertensive Disorders of Pregnancy.Current hypertension reports · 2020Review
- Immunometabolism during Mycobacterium tuberculosis Infection.Trends in microbiology · 2020Review
- Nitric Oxide in the Pathogenesis and Treatment of Tuberculosis.Frontiers in microbiology · 2017Review
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- Article
- Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.PloS one · 2014Article
- Reengineering redox sensitive GFP to measure mycothiol redox potential of Mycobacterium tuberculosis during infection.PLoS pathogens · 2014Article
- Impaired pulmonary nitric oxide bioavailability in pulmonary tuberculosis: association with disease severity and delayed mycobacterial clearance with treatment.The Journal of infectious diseases · 2013Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveThe relative contribution of nitric oxide (NO) to the killing of Mycobacterium tuberculosis in human tuberculosis (TB) is controversial, although this has been firmly established in rodents. Studies have demonstrated that clinical strains of M. tuberculosis differ in susceptibility to NO, but how this correlates to drug susceptibility and clinical outcome is not known.
methodsIn this study, 50 sputum smear- and culture-positive patients with pulmonary TB in Gondar, Ethiopia were included. Clinical parameters were recorded and drug susceptibility profile and spoligotyping patterns were investigated. NO susceptibility was studied by exposing the strains to the NO donor DETA/NO.
resultsClinical isolates of M. tuberculosis showed a dose- and time-dependent response when exposed to NO. The most frequent spoligotypes found were CAS1-Delhi and T3_ETH in a total of nine known spoligotypes and four orphan patterns. There was a significant association between reduced susceptibility to NO (>10% survival after exposure to 1 mM DETA/NO) and resistance against first-line anti-TB drugs, in particular isoniazid (INH). Patients infected with strains of M. tuberculosis with reduced susceptibility to NO showed no difference in cure rate or other clinical parameters but a tendency towards lower rate of weight gain after two months of treatment, independent of antibiotic resistance.
conclusionThere is a correlation between resistance to first-line anti-TB drugs and reduced NO susceptibility in clinical strains of M. tuberculosis. Further studies including the mechanisms of reduced NO susceptibility are warranted and could identify targets for new therapeutic interventions.
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