Prophages divert Staphylococcus aureus defenses against host lipids
2024
Zhou, Biyang | Pathania, Amit | Pant, Deepak | Halpern, David | Gaudu, Philippe | Trieu Cuot, Patrick | Dias-Leao, Andressa | Pagot, Charlotte | Solgadi, Audrey | Gruss, Alexandra | Gloux, Karine | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)) ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) | This work was supported by French granting agencies: French Agence Nationale de la Recherche (StaphEscape project ANR-16-CE15-0013), the Fondation pour la Recherche Medicale (DBF20161136769), and the INRAE’s department MICA (LipStaph project). | We thank Myriam Gominet (Institut Pasteur) for the construction of the S. aureus RN450 fakB1-repaired strain. We are grateful to members of the MicrobAdapt team for stimulating discussion of this work. | ANR-16-CE15-0013,StaphEscape,Résistance aux antimicrobiens par dormance transitoire et récupération: la voie de sortie peut-elle être bloquée ?(2016)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. Phages are ubiquitous in bacteria, including clinical Staphylococcus aureus, where Sfi 21/Sa3 phages often integrate into the hlb gene, which encodes Hlb sphingomyelinase. This integration acts as a rapid regulatory switch for Hlb production. Our findings suggest that Sfi 21/Sa3 prophages and Hlb activity influence S. aureus fitness by modulating the incorporation of the toxic linoleic acid (C18:2) from serum into the bacterial membrane. This process relies on C18:2 derived from 1,3-diglyceride, facilitated by the FakB1 kinase subunit. Palmitic acid (C16), primarily released from serum through Hlb activity, competes with C18:2 for FakB1. This mechanism contributes to adaptation to AFN-1252, an antibiotic inhibiting the fatty acid synthesis pathway (anti-FASII). Since S. aureus relies on exogenous fatty acids for growth, AFN-1252 treatment leads to increased proportion of C18:2 in the membrane. Furthermore, Hlb inhibition, whether by prophage insertion, gene inactivation, or enzyme inhibition, delays S. aureus adaptation, resulting in a higher proportion of C18:2 in the membrane. This study sheds light on the role of lipid environments in infections and may contribute to the accurate prediction of infection risks and therapeutic efficacy. Moreover, since both anti-FASII agent and Hlb inhibitor enhance C18:2 incorporation, they represent potential candidates for combined strategies against S. aureus.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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تم تزويد هذا السجل من قبل Institut national de la recherche agronomique