Key result
Codon adaptation index moderately correlates with in vitro protein expression in S. aureus.
Why the study?
Understanding of patterns in synonymous codon usage bias at the gene and genome levels, and how it impacts protein expression in Staphylococcus aureus, remains incomplete.
Codon bias in S. aureus varies between genes and isolates, and positively correlates with in vitro protein expression.
Answers are grounded in this paper and cite their sources.
May guide codon optimization in S. aureus systems; leaves open generalizability to other strains or in vivo settings.
Background Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. Methods The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. Results CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). Conclusions Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.
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O’Connor et al. (2026) studied Staphylococcus aureus. Codon bias (Codon adaptation index) was evaluated on Correlation between CAI and protein expression (cor = 0.534, p=< 2.2e-16). Codon adaptation index (CAI) and in vitro protein expression were moderately positively correlated in the LAC USA 300 strain of S. aureus.
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