ArticleGenome research2009
Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance.
Article in Genome research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
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Who cites it
49 citing papers in PubMed, 94 citations in OpenAlex.
- The emergence of linezolid resistance among Enterococci in intestinal microbiota of treated patients is unrelated to individual pharmacokinetic characteristics.Antimicrobial agents and chemotherapy · 2014Trial
- Resistance to linezolid in Staphylococcus aureus by mutation, modification, and acquisition of genes.The Journal of antibiotics · 2025Review
- Article
- Serotype distribution and antibiogram ofMicrobiology spectrum · 2023Article
- Pneumococcal within-host diversity during colonization, transmission and treatment.Nature microbiology · 2022Article
- Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis.Bone research · 2022Review
- Phenotypic Adaptation to Antiseptics and Effects on Biofilm Formation Capacity and Antibiotic Resistance in Clinical Isolates of Early Colonizers in Dental Plaque.Antibiotics (Basel, Switzerland) · 2022Article
- Article
- Gain- and Loss-of-Function Screens Coupled to Next-Generation Sequencing for Antibiotic Mode of Action and Resistance Studies inAntimicrobial agents and chemotherapy · 2019Article
- Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq).Genome medicine · 2018Article
- Comparative genomic analysis of ten clinical Streptococcus pneumoniae collected from a Malaysian hospital reveal 31 new unique drug-resistant SNPs using whole genome sequencing.Journal of biomedical science · 2018Article
- Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective.Clinical microbiology reviews · 2016Review
- Evolution of Bacterial Pathogens Within the Human Host.Microbiology spectrum · 2016Review
- A genomic approach to understand interactions between Streptococcus pneumoniae and its bacteriophages.BMC genomics · 2015Article
- Differences in antibiotic-induced oxidative stress responses between laboratory and clinical isolates of Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2015Article
- Whole-genome sequencing targets drug-resistant bacterial infections.Human genomics · 2015Review
- Multiple mutations and increased RNA expression in tetracycline-resistant Streptococcus pneumoniae as determined by genome-wide DNA and mRNA sequencing.The Journal of antimicrobial chemotherapy · 2015Article
- Mobile elements and chromosomal changes associated with MLS resistance phenotypes of invasive pneumococci recovered in the United States.Microbial drug resistance (Larchmont, N.Y.) · 2015Article
- A novel gene amplification causes upregulation of the PatAB ABC transporter and fluoroquinolone resistance in Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2015Article
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Linezolid is a member of a novel class of antibiotics, with resistance already being reported. We used whole-genome sequencing on three independent Streptococcus pneumoniae strains made resistant to linezolid in vitro in a step-by-step fashion. Analysis of the genome assemblies revealed mutations in the 23S rRNA gene in all mutants including, notably, G2576T, a previously recognized resistance mutation. Mutations in an additional 31 genes were also found in at least one of the three sequenced genomes. We concentrated on three new mutations that were found in at least two independent mutants. All three mutations were experimentally confirmed to be involved in antibiotic resistance. Mutations upstream of the ABC transporter genes spr1021 and spr1887 were correlated with increased expression of these genes and neighboring genes of the same operon. Gene inactivation supported a role for these ABC transporters in resistance to linezolid and other antibiotics. The hypothetical protein spr0333 contains an RNA methyltransferase domain, and mutations within that domain were found in all S. pneumoniae linezolid-resistant strains. Primer extension experiments indicated that spr0333 methylates G2445 of the 23S rRNA and mutations in spr0333 abolished this methylation. Reintroduction of a nonmutated version of spr0333 in resistant bacteria reestablished G2445 methylation and led to cells being more sensitive to linezolid and other antibiotics. Interestingly, the spr0333 ortholog was also mutated in a linezolid-resistant clinical Staphylococcus aureus isolate. Whole-genome sequencing and comparative analyses of S. pneumoniae resistant isolates was useful for discovering novel resistance mutations.
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Registered trials
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.