ArticlePLoS pathogens2019
Multi-strain Tn-Seq reveals common daptomycin resistance determinants in Staphylococcus aureus.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Applications of transposon-insertion sequencing for understanding bacterial physiology.Microbial genomics · 2026Review
- A subclade-associated genomic deletion encompassing vraDEH confers increased susceptibility to nisin A and bacitracin in Staphylococcus aureus CC121.Scientific reports · 2026Article
- Alanine Uptake Is Required to MaintainMicroorganisms · 2026Article
- D-alanine aminotransferase (Dat) promotesbioRxiv : the preprint server for biology · 2026Article
- Profiling of genetic determinants required for fitness of community-associated methicillin-resistantMicrobiology spectrum · 2026Article
- Tunable TriPcides suppress virulence factor secretion duringScience advances · 2026Article
- The genetic landscape of antibiotic sensitivity inScience advances · 2026Article
- Genome-wide association analysis provides insights into the genomics and extracellular expression ofVirulence · 2025Article
- Article
- Quantitative essentiality in a reduced genome: a functional, regulatory and structural fitness map.Molecular systems biology · 2025Article
- Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus.Nature communications · 2025Article
- SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes.Journal of visualized experiments : JoVE · 2025Article
- Transposon-sequencing across multiplemBio · 2025Article
- The Secondary Resistome of Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2025Article
- Essential Genes Discovery in Microorganisms by Transposon-Directed Sequencing (Tn-Seq): Experimental Approaches, Major Goals, and Future Perspectives.International journal of molecular sciences · 2024Review
- Optimizing phage-based mutant recovery and minimizing heat effect in the construction of transposon libraries in Staphylococcus aureus.Scientific reports · 2024Article
- Article
- Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance.Journal of bacteriology · 2024Review
- Article
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Authors and funding
7 authors.
Funding
Abstract
Antibiotic-resistant Staphylococcus aureus remains a leading cause of antibiotic resistance-associated mortality in the United States. Given the reality of multi-drug resistant infections, it is imperative that we establish and maintain a pipeline of new compounds to replace or supplement our current antibiotics. A first step towards this goal is to prioritize targets by identifying the genes most consistently required for survival across the S. aureus phylogeny. Here we report the first direct comparison of multiple strains of S. aureus via transposon sequencing. We show that mutant fitness varies by strain in key pathways, underscoring the importance of using more than one strain to differentiate between core and strain-dependent essential genes. We treated the libraries with daptomycin to assess whether the strain-dependent differences impact pathways important for survival. Despite baseline differences in gene importance, several pathways, including the lipoteichoic acid pathway, consistently promote survival under daptomycin exposure, suggesting core vulnerabilities that can be exploited to resensitize daptomycin-nonsusceptible isolates. We also demonstrate the merit of using transposons with outward-facing promoters capable of overexpressing nearby genes for identifying clinically-relevant gain-of-function resistance mechanisms. Together, the daptomycin vulnerabilities and resistance mechanisms support a mode of action with wide-ranging effects on the cell envelope and cell division. This work adds to a growing body of literature demonstrating the nuanced insights gained by comparing Tn-Seq results across multiple bacterial strains.
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