ArticleBMC microbiology2008
Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia.
Article in BMC microbiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 3 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 3 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- The global scope of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA): a meta-analysis of its clinical impact, molecular epidemiology, and diagnostic challenges across 15,165 isolates.BMC infectious diseases · 2026Pooled it
- The Effectiveness of Oral Vancomycin on Inflammatory Bowel Disease in Patients With Primary Sclerosing Cholangitis: A Systematic Review.Inflammatory bowel diseases · 2025Pooled it
- Systematic review and meta-analysis of the significance of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates.Antimicrobial agents and chemotherapy · 2011Pooled it
- Optimizing phage-antibiotic combinations: impact of administration order against daptomycin non-susceptible (DNS) MRSA clinical isolates.Antimicrobial agents and chemotherapy · 2025Article
- Acquisition of daptomycin resistance in patients results in decreased virulence inInfection and immunity · 2025Article
- AgrA directly binds to the promoter ofAntimicrobial agents and chemotherapy · 2024Article
- Effects of Vancomycin Subtherapeutic Concentration on Staphylococcus aureus Isolated from Hemodialysis Patients with Low Serum Trough Concentrations.Current microbiology · 2024Article
- Transposon sequencing identifies genes impactingInfection and immunity · 2023Article
- New Antimicrobial Resistance Strategies: An Adaptive Resistance Network Conferring Reduced Glycopeptide Susceptibility in VISA.Antibiotics (Basel, Switzerland) · 2023Article
- The Role of β-Glycosylated Wall Teichoic Acids in the Reduction of Vancomycin Susceptibility in Vancomycin-Intermediate Staphylococcus aureus.Microbiology spectrum · 2021Article
- Environmental conditions dictate differential evolution of vancomycin resistance in Staphylococcus aureus.Communications biology · 2021Article
- The Gut-Liver Axis in Cholestatic Liver Diseases.Nutrients · 2021Review
- The extracellular loop of the membrane permease VraG interacts with GraS to sense cationic antimicrobial peptides in Staphylococcus aureus.PLoS pathogens · 2021Article
- Review
- The role of oral vancomycin in inducing remission for biologic-experienced ulcerative colitis with concomitant primary sclerosing cholangitis and liver transplantation.Clinical journal of gastroenterology · 2021Article
- Acapsular Staphylococcus aureus with a non-functional agr regains capsule expression after passage through the bloodstream in a bacteremia mouse model.Scientific reports · 2020Article
- Interleukin (IL)-1β and IL-10 Host Responses in Patients With Staphylococcus aureus Bacteremia Determined by Antimicrobial Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms.FEMS microbiology reviews · 2020Review
- Antibiotic Resistance and the MRSA Problem.Microbiology spectrum · 2019Review
- Absence of Protein A Expression Is Associated With Higher Capsule Production in Staphylococcal Isolates.Frontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLow-level vancomycin resistance in Staphylococcus aureus (vancomycin-intermediate S. aureus (VISA) and hetero-VISA [hVISA]) emerges during persistent infection and failed vancomycin therapy. Up-regulation of genes associated with the "cell wall stimulon" and mutations in the vraSR operon have both been implicated in the development of resistance, however the molecular mechanisms of resistance are not completely understood. To further elucidate the mechanisms leading to resistance transcriptome comparisons were performed using multiple clinical pairs of vancomycin-susceptible S. aureus (VSSA) and hVISA/VISA (n = 5), and three VSSA control pairs from hospitalized patients with persistent bacteraemia that did not develop hVISA/VISA. Based on the transcriptome results multiple genes were sequenced and innate immune system stimulation was assessed in the VSSA and hVISA/VISA pairs.
resultsHere we show that up-regulation of vraS and the "cell wall stimulon" is not essential for acquisition of low-level vancomycin resistance and that different transcriptional responses occur, even between closely related hVISA/VISA strains. DNA sequencing of vraSR, saeSR, mgrA, rot, and merR regulatory genes and upstream regions did not reveal any differences between VSSA and hVISA/VISA despite transcriptional changes suggesting mutations in these loci may be linked to resistance in these strains. Enhanced capsule production and reduced protein A expression in hVISA/VISA were confirmed by independent bioassays and fully supported the transcriptome data. None of these changes were observed in the three control pairs that remained vancomycin-susceptible during persistent bacteremia. In a macrophage model of infection the changes in cell surface structures in hVISA/VISA strains were associated with significantly reduced NF-kappaB activation resulting in reduced TNF-alpha and IL-1beta expression.
conclusionWe conclude that there are multiple pathways to low-level vancomycin resistance in S. aureus, even among closely related clinical strains, and these can result in an attenuated host immune response. The persistent infections associated with hVISA/VISA strains may be a consequence of changes in host pathogen interactions in addition to the reduced antibiotic susceptibility.
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