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A periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginos

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dc.contributor.authorGuest, Randi L.
dc.contributor.authorLee Michael J.
dc.contributor.authorWang, Wei
dc.contributor.authorSilhavy, Thomas J.
dc.date.accessioned2025-02-03T17:25:46Z
dc.date.available2025-02-03T17:25:46Z
dc.date.issued2023
dc.description.abstractThe outer membrane of Gram-negative bacteria is unique in both structure and function. The surface-exposed outer leaflet is composed of lipopolysaccharide, while the inner leaflet is composed of glycerophospholipids. This lipid asymmetry creates mechanical strength, lowers membrane permeability, and is necessary for virulence in many pathogens. Glycerophospholipids that mislocalize to the outer leaflet are removed by the Mla pathway, which consists of the outer membrane channel MlaA, the periplasmic lipid carrier MlaC, and the inner membrane transporter MlaBDEF. The opportunistic pathogen Pseudomonas aeruginosa has two proteins of the MlaA family: PA2800 and PA3239. Here, we show that PA2800 is part of a canonical Mla pathway, while PA3239 functions with the putative lipase PA3238. While loss of either pathway individually has little to no effect on outer membrane integrity, loss of both pathways weakens the outer membrane permeability barrier and increases production of the secondary metabolite pyocyanin. We propose that mislocalized glycerophospholipids are removed from the outer leaflet by PA3239 (renamed MlaZ), transferred to PA3238 (renamed MlaY), and degraded. This pathway streamlines recycling of glycerophospholipid degradation products by removing glycerophospholipids from the outer leaflet prior to degradation.
dc.identifier.citationGuest, R. L., Lee, M. J., Wang, W., & Silhavy, T. J. (2023). A periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginosa. PNAS. 120(30), e2302546120. https://doi.org/10.1073/pnas.2302546120
dc.identifier.doihttps://doi.org/10.1073/pnas.2302546120
dc.identifier.urihttps://hdl.handle.net/20.500.14078/3782
dc.language.isoen
dc.rightsAttribution-NonCommercial-NoDerivs (CC BY-NC-ND)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectouter membrane
dc.subjectMla pathway
dc.subjectPA2800
dc.subjectPA3238
dc.subjectPA3239
dc.titleA periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginosen
dc.typeArticle

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