Prophages divert Staphylococcus aureus defenses against host lipids.
Biyang Zhou1, Amit Pathania1, Deepak Pant1
1Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy en Josas, France.
Journal of Lipid Research
|November 6, 2024
Summary
Bacteriophages (Sfi 21/Sa3) regulate Staphylococcus aureus fitness by controlling linoleic acid incorporation into membranes. This mechanism impacts adaptation to fatty acid synthesis inhibitors, suggesting new therapeutic strategies.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Phages are common in Staphylococcus aureus, with Sfi 21/Sa3 phages integrating into the hlb gene.
- This integration regulates Hlb sphingomyelinase production, affecting bacterial membrane composition.
Purpose of the Study:
- To investigate how Sfi 21/Sa3 prophages and Hlb activity influence Staphylococcus aureus fitness.
- To elucidate the role of lipid metabolism and membrane fatty acid incorporation in bacterial adaptation.
Main Methods:
- Analysis of phage integration and its effect on Hlb activity.
- Investigating the incorporation of linoleic acid (C18:2) and palmitic acid (C16) into bacterial membranes.
- Assessing bacterial adaptation to anti-fatty acid synthesis inhibitors (anti-FASII) like AFN-1252.
Main Results:
- Sfi 21/Sa3 prophage integration and Hlb activity modulate C18:2 incorporation, influenced by FakB1 and competing C16.
- Hlb inhibition, via prophage, gene inactivation, or enzyme inhibition, delays bacterial adaptation to anti-FASII agents.
- Increased C18:2 proportion in membranes is observed under anti-FASII treatment and Hlb inhibition.
Conclusions:
- Bacterial lipid environments play a crucial role in infection dynamics and therapeutic responses.
- Combined strategies using anti-FASII agents and Hlb inhibitors show promise for treating Staphylococcus aureus infections.
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