ArticleAntimicrobial agents and chemotherapy2013
Comprehensive identification of mutations responsible for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA)-to-VISA conversion in laboratory-generated VISA strains derived from hVISA clinical strain Mu3.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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38 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled it
- Phosphorylation by the PknB Serine/Threonine Kinase Stimulates Dimer Formation by WalR.Biochemistry · 2026Article
- Bacterial heteroresistance mechanisms, dynamics, and emerging diagnostic approaches.Bioscience reports · 2026Review
- A Single Point Mutation in GraS Drives Co-Evolution of Vancomycin Resistance and Virulence inMicroorganisms · 2026Article
- Review
- A benzoxazolyl urea inhibits VraS and enhances antimicrobials against vancomycin intermediate-resistant Staphylococcus aureus.Bioorganic & medicinal chemistry letters · 2025Article
- Prevention and potential remedies for antibiotic resistance: current research and future prospects.Frontiers in microbiology · 2024Review
- High prevalence of heteroresistance in Staphylococcus aureus is caused by a multitude of mutations in core genes.PLoS biology · 2024Article
- Analysis ofBioinformation · 2024Article
- Adaptive Laboratory Evolution ofAntibiotics (Basel, Switzerland) · 2023Article
- Interplays of mutations inFrontiers in cellular and infection microbiology · 2023Article
- Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America.The Journal of antimicrobial chemotherapy · 2022Article
- Article
- Mass spectrometry and machine learning for the accurate diagnosis of benzylpenicillin and multidrug resistance of Staphylococcus aureus in bovine mastitis.PLoS computational biology · 2021Article
- Article
- Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America.The Journal of antimicrobial chemotherapy · 2020Article
- Role of theAntimicrobial agents and chemotherapy · 2019Article
- The Staphylococcal Cell Wall.Microbiology spectrum · 2019Review
- Antibiotic Resistance and the MRSA Problem.Microbiology spectrum · 2019Review
- Identification of a Novel Gene Associated with High-Level β-Lactam Resistance in Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain Mu3 and Methicillin-Resistant S. aureus Strain N315.Antimicrobial agents and chemotherapy · 2019Article
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4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) spontaneously produces VISA cells within its cell population at a frequency of 10(-6) or greater. We established a total of 45 VISA mutant strains independently obtained from hVISA Mu3 and its related strains by one-step vancomycin selection. We then performed high-throughput whole-genome sequencing of the 45 strains and their parent strains to identify the genes involved in the hVISA-to-VISA phenotypic conversion. A comparative genome study showed that all the VISA strains tested carried a unique set of mutations. All of the 45 VISA strains carried 1 to 4 mutations possibly affecting the expression of a total of 48 genes. Among them, 32 VISA strains carried only one gene affected by a single mutation. As many as 20 genes in more than eight functional categories were affected in the 32 VISA strains, which explained the extremely high rates of the hVISA-to-VISA phenotypic conversion. Five genes, rpoB, rpoC, walK, pbp4, and pp2c, were previously reported as being involved in vancomycin resistance. Fifteen remaining genes were newly identified as associated with vancomycin resistance in this study. The gene most frequently affected (6 out of 32 strains) was cmk, which encodes cytidylate kinase, followed closely by rpoB (5 out of 32), encoding the β subunit of RNA polymerase. A mutation prevalence study also revealed a sizable number of cmk mutants among clinical VISA strains (7 out of 38 [18%]). Reduced cytidylate kinase activity in cmk mutant strains is proposed to contribute to the hVISA-to-VISA phenotype conversion by thickening the cell wall and reducing the cell growth rate.
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