ArticleAntimicrobial agents and chemotherapy2015
Stepwise decrease in daptomycin susceptibility in clinical Staphylococcus aureus isolates associated with an initial mutation in rpoB and a compensatory inactivation of the clpX gene.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- The global prevalence of Daptomycin, Tigecycline, Quinupristin/Dalfopristin, and Linezolid-resistant Staphylococcus aureus and coagulase-negative staphylococci strains: a systematic review and meta-analysis.Antimicrobial resistance and infection control · 2020Pooled it
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- Methicillin-Resistant Staphylococcus aureus Bacteremia Relapses Show Diverse Genomic Profiles but Convergence in Bacteremia-Associated Genes.The Journal of infectious diseases · 2025Article
- Unraveling proteomic chaos by independent component analysis-ClpX proficiency promotes the iron and oxygen limitation responses ofmSystems · 2025Article
- The ClpXP protease and the ClpX unfoldase control virulence, cell division, and autolysis inMicrobiology spectrum · 2025Article
- Characterisation ofJAC-antimicrobial resistance · 2025Article
- Detection of virulence factors in opportunistic bacteria: advances, challenges, and practical implementation.Frontiers in microbiology · 2025Review
- Understanding the selectivityFrontiers in bioinformatics · 2025Article
- ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics.Nature reviews. Microbiology · 2024Review
- The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistantAntimicrobial agents and chemotherapy · 2024Article
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- Human milk oligosaccharides regulate human macrophage polarization and activation in response toFrontiers in immunology · 2024Article
- Molecular Characteristics and Prevalence of Rifampin Resistance inAntibiotics (Basel, Switzerland) · 2023Article
- A Clinically Selected Staphylococcus aureusAntimicrobial agents and chemotherapy · 2023Article
- Effect of Antibiotic Exposure onInternational journal of molecular sciences · 2023Article
- Review
- Cervimycin-Resistant Staphylococcus aureus Strains Display Vancomycin-Intermediate Resistant Phenotypes.Microbiology spectrum · 2022Article
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Daptomycin is a lipopeptide antibiotic used clinically for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. The emergence of daptomycin-nonsusceptible S. aureus isolates during therapy is often associated with multiple genetic changes; however, the relative contributions of these changes to resistance and other phenotypic changes usually remain unclear. The present study was undertaken to investigate this issue using a genetically characterized series of four isogenic clinical MRSA strains derived from a patient with bacteremia before and during daptomycin treatment. The first strain obtained after daptomycin therapy carried a single-nucleotide polymorphism (SNP) in rpoB (RpoB A477D) that decreased susceptibility not only to daptomycin but also to vancomycin, β-lactams, and rifampin. Furthermore, the rpoB mutant exhibited pleiotropic phenotypes, including increased cell wall thickness, reduced expression of virulence traits, induced expression of the stress-associated transcriptional regulator Spx, and slow growth. A subsequently acquired loss-of-function mutation in clpX partly alleviated the growth defect conferred by the rpoB mutation without changing antibiotic susceptibility. The final isolate acquired three additional mutations, including an SNP in mprF (MprF S295L) known to confer daptomycin nonsusceptibility, and accordingly, this isolate was the only daptomycin-nonsusceptible strain of this series. Interestingly, in this isolate, the cell wall had regained the same thickness as that of the parental strain, while the level of transcription of the vraSR (cell wall stress regulator) was increased. In conclusion, this study illustrates how serial genetic changes selected in vivo contribute to daptomycin nonsusceptibility, growth fitness, and virulence traits.
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