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Date publication

février 2026

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Dr KLAHOLZ Bruno , Dr ROMBY Pascale


Tous les auteurs :
Kohl MP, Bahena-Ceron R, Chane-Woon-Ming B, Kompatscher M, Erlacher MD, Barchet C, von Loeffelholz O, Romby P, Klaholz BP, Marzi S

Résumé

Regulation 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.

Référence

Nat Commun. 2026 02 12;: