ArticlePLoS genetics2018
Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Whole-Exome Sequencing for the Identification of Genetic Factors Implicated in Severe Bacterial Infections: A Systematic Review.The Journal of infectious diseases · 2026Pooled it
- Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment.Nature reviews. Microbiology · 2026Review
- The lack of a biorepository during vaccine trials: A lost opportunity to understand staphylococcal immunity.Vaccine · 2025Article
- Host DNA damage and cellular fate in bacterial infections, with a focus on Staphylococcus aureus.FEMS microbiology reviews · 2025Review
- Staphylococcus aureus host interactions and adaptation.Nature reviews. Microbiology · 2023Review
- All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: Results of GWAS and experimental animal studies.The Journal of infection · 2023Article
- Disentangling Independent and Mediated Causal Relationships Between Blood Metabolites, Cognitive Factors, and Alzheimer's Disease.Biological psychiatry global open science · 2022Article
- Microbiome, Transcriptome, and Metabolomic Analyses Revealed the Mechanism of Immune Response to Diarrhea in Rabbits Fed Antibiotic-Free Diets.Frontiers in microbiology · 2022Article
- Review
- Sequencing-based genome-wide association studies reporting standards.Cell genomics · 2021Article
- Association of variants in selected genes mediating host immune response with duration of Staphylococcus aureus bacteremia.Genes and immunity · 2020Article
- Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms.FEMS microbiology reviews · 2020Review
- Risk stratification biomarkers forClinical & translational immunology · 2020Article
- Using genomics to understand meticillin- and vancomycin-resistantMicrobial genomics · 2020Review
- Genetic variation of DNA methyltransferase-3A contributes to protection against persistent MRSA bacteremia in patients.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
29 authors at 11 institutions in 2 countries.
Funding
Abstract
The role of host genetic variation in the development of complicated Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome sequencing (WES) to examine the cumulative effect of coding variants in each gene on risk of complicated SAB in a discovery sample of 168 SAB cases (84 complicated and 84 uncomplicated, frequency matched by age, sex, and bacterial clonal complex [CC]), and then evaluated the most significantly associated genes in a replication sample of 240 SAB cases (122 complicated and 118 uncomplicated, frequency matched for age, sex, and CC) using targeted sequence capture. In the discovery sample, gene-based analysis using the SKAT-O program identified 334 genes associated with complicated SAB at p<3.5 x 10-3. These, along with eight biologically relevant candidate genes were examined in the replication sample. Gene-based analysis of the 342 genes in the replication sample using SKAT-O identified one gene, GLS2, significantly associated with complicated SAB (p = 1.2 x 10-4) after Bonferroni correction. In Firth-bias corrected logistic regression analysis of individual variants, the strongest association across all 10,931 variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10-4). This variant is strongly correlated with a missense variant (rs2657879, p = 4.4 x 10-3) in which the minor allele (associated here with complicated SAB) has been previously associated with lower plasma concentration of glutamine. In a microarray-based gene-expression analysis, individuals with SAB exhibited significantly lower expression levels of GLS2 than healthy controls. Similarly, Gls2 expression is lower in response to S. aureus exposure in mouse RAW 264.7 macrophage cells. Compared to wild-type cells, RAW 264.7 cells with Gls2 silenced by CRISPR-Cas9 genome editing have decreased IL1-β transcription and increased nitric oxide production after S. aureus exposure. GLS2 is an interesting candidate gene for complicated SAB due to its role in regulating glutamine metabolism, a key factor in leukocyte activation.
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Registered trials
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