ArticleThe Journal of antimicrobial chemotherapy2025
The toxin-antitoxin system SavRS contributes to vancomycin resistance in vancomycin-intermediate Staphylococcus aureus by mediating cell wall thickening.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
backgroundThe emergence of vancomycin-intermediate Staphylococcus aureus (VISA) has significantly challenged the treatment of S. aureus infection. Toxin-antitoxin (TA) systems have been reported to mediate bacterial stress adaptation and virulence, but their role in vancomycin resistance remains elusive. This study investigated the vancomycin resistance mechanism regulated by the TA system SavRS in VISA.
methodssavRS mutants in Mu50 and XN108 were generated via homologous recombination. To investigate the regulatory mechanism of vancomycin resistance mediated by savRS in VISA, phenotypic analyses including MICs, growth kinetics and cell wall thickness measurements were performed. Expression of cell wall synthesis-related genes was analysed using quantitative RT-PCR (RT-qPCR) and promoter-lacZ reporter assay. Electrophoretic mobility shift assay (EMSA) was performed to assess the binding of SavRS to the promoters of the cell wall synthesis-related genes. Pull-down assay identified an upstream regulatory element of savRS associated with vancomycin resistance. Quantitative assessment of bacterial burden in murine organ systems following vancomycin administration revealed the critical regulatory role of savRS in mediating vancomycin resistance in vivo.
resultsCompared with the WT, the savRS mutant exhibited enhanced vancomycin sensitivity, accelerated growth and reduced cell wall thickness. Correspondingly, RT-qPCR revealed marked down-regulation of the cell wall synthesis-related genes (glyS, dltA, scdA, pbp2, ddl). EMSA and promoter-lacZ reporter assay confirmed direct binding of SavRS to a conserved promoter motif, MGHYYTCCTCA. Pull-down assay identified UspA as an upstream regulator of SavRS, demonstrating that UspA directly controls savRS transcription and modulates VISA resistance. Mouse infection experiments showed that savRS promotes VISA to vancomycin resistance in vivo.
conclusionsSavRS critically regulates vancomycin resistance in VISA.
Indexed as
Identifiers
What OpenQuestion holds
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.