Phosphate-responsive ornithine lipid biosynthesis remodels outer membrane composition and contributes to polymyxin tolerance

In Enterobacter cloacae and Klebsiella pneumoniae, phosphate limitation triggers OlsF-dependent ornithine lipid accumulation that enriches in the outer membrane and enhances polymyxin tolerance.

• Why it matters: Phosphate scarcity limits phospholipid synthesis and threatens Gram-negative envelope integrity, but how Enterobacterales remodel membranes and alter antibiotic susceptibility is unclear.
• What they did: The study mapped OL biosynthesis genetics and physiology, showing OL formation requires OlsF, regulated by the PhoBR two-component system under phosphate limitation. Membrane fractionation then assessed OL distribution across compartments.
• The result: OlsF-derived OLs were detected in both membrane fractions but were enriched in the outer membrane, and OlsF-dependent OL production increased polymyxin tolerance specifically during phosphate limitation.

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