Structural highlights
Publication Abstract from PubMedRegulation of translation initiation is central to bacterial adaptation, but species-specific mechanisms remain poorly understood. We present high-resolution mapping of translation start sites in Staphylococcus aureus, revealing distinct features of initiation alongside numerous unannotated small ORFs. Our analysis, combined with cryo-EM of a native mRNA-ribosome complex, shows that S. aureus relies on extended, start codon proximal Shine-Dalgarno (SD) interactions, creating specificity against phylogenetically distant bacteria. Several natural S. aureus initiation sites are not correctly decoded by E. coli ribosomes. We identify new and conserved non-canonical start codons, whose regulatory initiation sites contain these characteristic extended SD sequence motifs. Finally, we characterize a novel example of uORF-mediated translational control in S. aureus, demonstrating that translation of a small leader peptide modulates expression of a key biofilm regulator. The described mechanism involves codon rarity, ribosome pausing, and arginine availability, linking nutrient sensing to biofilm formation in this major human pathogen. Extended Shine-Dalgarno motifs govern translation initiation in Staphylococcus aureus.,Kohl MP, Bahena-Ceron R, Chane-Woon-Ming B, Kompatscher M, Erlacher MD, Barchet C, von Loeffelholz O, Romby P, Klaholz BP, Marzi S Nat Commun. 2026 Feb 12. doi: 10.1038/s41467-026-69079-8. PMID:41680142[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 07:42, 25 February 2026.