ArticleNature genetics2016
Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance.
Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 178 citations in OpenAlex.
- In Host Mutational Adaptation of Mycobacterium Tuberculosis Complex Strains During Tuberculosis Infection.The Journal of infectious diseases · 2026Pooled it
- d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- Rapid drug resistance prediction in positiveEmerging microbes & infections · 2026Article
- The structural context of mutations in proteins predicts their effect on antibiotic resistance.eLife · 2026Article
- Genome shuffling enables quantitative trait locus mapping in Bacillus subtilis.Nature communications · 2026Article
- Drug resistance mechanisms inFrontiers in pharmacology · 2026Review
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- An explainable artificial intelligence framework reveals mutations associated with drug resistance inBiosafety and health · 2025Article
- Unraveling Epistatic Interactions Between Sites Under Drug-Dependent Selection in the Mycobacterium tuberculosis Genome.Molecular biology and evolution · 2025Article
- Cycloserine resistance among drug-resistant tuberculosis cases in Taiwan.Microbiology spectrum · 2025Article
- Integrating genomic, transcriptomic, and phenotypic information to explore drug resistance in Mycobacterium tuberculosis sub-lineage 4.2.2.2.Journal of applied microbiology · 2025Article
- Complex exchanges among plasmids and clonal expansion of lineages shape the population structure and virulence ofbioRxiv : the preprint server for biology · 2025Article
- Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dual transcriptional inhibition of glutamate and alanine racemase is synergistic inMicrobiology (Reading, England) · 2024Article
- Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine.Nature communications · 2024Article
- The efflux pumps Rv1877 and Rv0191 play differential roles in the protection ofFrontiers in microbiology · 2024Article
- Identification ofInfection and drug resistance · 2024Review
- OvercomingACS omega · 2023Review
- Analysis of Genome-Wide Mutational Dependence in Naturally Evolving Mycobacterium tuberculosis Populations.Molecular biology and evolution · 2023Article
- Heterologous production of the D-cycloserine intermediate O-acetyl-L-serine in a human type II pulmonary cell model.Scientific reports · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
A more complete understanding of the genetic basis of drug resistance in Mycobacterium tuberculosis is critical for prompt diagnosis and optimal treatment, particularly for toxic second-line drugs such as D-cycloserine. Here we used the whole-genome sequences from 498 strains of M. tuberculosis to identify new resistance-conferring genotypes. By combining association and correlated evolution tests with strategies for amplifying signal from rare variants, we found that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, were associated with unexplained drug resistance. Convergent evolution of this loss of function was observed exclusively among multidrug-resistant strains. Drug susceptibility testing established that ald loss of function conferred resistance to D-cycloserine, and susceptibility to the drug was partially restored by complementation of ald. Clinical strains with mutations in ald and alr exhibited increased resistance to D-cycloserine when cultured in vitro. Incorporation of D-cycloserine resistance in novel molecular diagnostics could allow for targeted use of this toxic drug among patients with susceptible infections.
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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.