ArticleBMC genomics2017
RNA-seq and Tn-seq reveal fitness determinants of vancomycin-resistant Enterococcus faecium during growth in human serum.
Article in BMC genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 64 citations in OpenAlex.
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- Cellodextrin Metabolism and Phosphotransferase System-Catalyzed Uptake in Enterococcus faecalis.Molecular microbiology · 2025Article
- Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization.Cell reports · 2025Article
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- Enterococcus faecium: evolution, adaptation, pathogenesis and emerging therapeutics.Nature reviews. Microbiology · 2024Review
- Determinants of bacterial survival and proliferation in blood.FEMS microbiology reviews · 2024Review
- Genome-wide analysis of acid tolerance genes of Enterococcus faecalis with RNA-seq and Tn-seq.BMC genomics · 2024Article
- Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain.npj antimicrobials and resistance · 2024Article
- Purine and carbohydrate availability drivemBio · 2024Article
- Interactions between commensalFEMS microbes · 2024Article
- Colonization of vancomycin-resistantFEMS microbes · 2024Article
- Activity-based protein profiling of serine hydrolases and penicillin-binding proteins inFEMS microbes · 2024Article
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- Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts.Microbial genomics · 2023Article
- A moonlighting role for LysM peptidoglycan binding domains underpins Enterococcus faecalis daughter cell separation.Communications biology · 2023Article
- Mitoxantrone targets both host and bacteria to overcome vancomycin resistance inScience advances · 2023Article
- New Insights into the Lactic Acid Resistance Determinants of Listeria monocytogenes Based on Transposon Sequencing and Transcriptome Sequencing Analyses.Microbiology spectrum · 2023Article
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundThe Gram-positive bacterium Enterococcus faecium is a commensal of the human gastrointestinal tract and a frequent cause of bloodstream infections in hospitalized patients. The mechanisms by which E. faecium can survive and grow in blood during an infection have not yet been characterized. Here, we identify genes that contribute to growth of E. faecium in human serum through transcriptome profiling (RNA-seq) and a high-throughput transposon mutant library sequencing approach (Tn-seq).
resultsWe first sequenced the genome of E. faecium E745, a vancomycin-resistant clinical isolate, using a combination of short- and long read sequencing, revealing a 2,765,010 nt chromosome and 6 plasmids, with sizes ranging between 9.3 kbp and 223.7 kbp. We then compared the transcriptome of E. faecium E745 during exponential growth in rich medium and in human serum by RNA-seq. This analysis revealed that 27.8% of genes on the E. faecium E745 genome were differentially expressed in these two conditions. A gene cluster with a role in purine biosynthesis was among the most upregulated genes in E. faecium E745 upon growth in serum. The E. faecium E745 transposon mutant library was then used to identify genes that were specifically required for growth of E. faecium in serum. Genes involved in de novo nucleotide biosynthesis (including pyrK_2, pyrF, purD, purH) and a gene encoding a phosphotransferase system subunit (manY_2) were thus identified to be contributing to E. faecium growth in human serum. Transposon mutants in pyrK_2, pyrF, purD, purH and manY_2 were isolated from the library and their impaired growth in human serum was confirmed. In addition, the pyrK_2 and manY_2 mutants were tested for their virulence in an intravenous zebrafish infection model and exhibited significantly attenuated virulence compared to E. faecium E745.
conclusionsGenes involved in carbohydrate metabolism and nucleotide biosynthesis of E. faecium are essential for growth in human serum and contribute to the pathogenesis of this organism. These genes may serve as targets for the development of novel anti-infectives for the treatment of E. faecium bloodstream infections.
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