• Citer

Discovery and Characterization of Selective Bacteriocins for the Treatment of Staphylococcus aureus

par Jaumaux, Félix
Président du jury Van Melderen, Laurence
Promoteur Govaerts, Cédric
Co-Promoteur Garcia-Pino, Abel
Publication Non publié, 2023-11-15

Thèse de doctorat

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

The emergence of antibiotic-resistant Staphylococcus aureus has become a major public health concern, necessitating the discovery of new antimicrobial compounds. Given that the skin microbiome plays a critical role in the host defense against pathogens, the development of therapies that target the interactions between commensal bacteria and pathogens in the skin microbiome offers a promising approach. Here, we report the discovery of two bacteriocins, cerein 7B and cerein B4080, that selectively inhibit S. aureus without affecting Staphylococcus epidermidis, a commensal bacterium on the skin.In this study, structural and mutational characterization of cerein 7B allowed us to propose a hypothesis of the mechanism of action for this bacteriocin, where it is believed to accumulate at the cell membrane, inducing the formation of pores. Furthermore, the study revealed that exposure of S. aureus to both discovered bacteriocins resulted in mutations in the walK/R two-component system, leading to a thickening of the cell wall visible by transmission electron microscopy and subsequent decreased sensitivity to vancomycin. Following RNA sequencing results indicate an upregulation of genes known to enhance the abundance of positively charged components at the cell membrane, thereby resulting in reduced sensitivity to other cationic bacteriocins.Our findings prompt a nuanced discussion of the potential of those bacteriocins for selective targeting of S. aureus on the skin, given the emergence of resistance and co-resistance with vancomycin. The idea put forward implies that by preserving commensal bacteria, selective compounds could limit the emergence of resistance in pathogenic cells by promoting competition with remaining commensal bacteria, ultimately reducing chronic infections and limiting the spread of antibiotic resistance.