title: Heterologous expression of 3-O-deacylase in Acinetobacter baumannii modulates the endotoxicity of lipopolysaccharide.
abstract: The lipopolysaccharide (LPS) of Acinetobacter baumannii is a potent stimulator of proinflammatory cytokines, such as interleukin-6 (IL-6). The 3-O-deacylase (PagL)-modifying enzyme that removes the 3-O-linked acyl chain from the disaccharide backbone of lipid A provides the opportunity to develop a new therapeutic compound that could reduce detrimental inflammatory responses. The plasmid pMMB66EH-PagL obtained by recombinant DNA technology was electroporated into A. baumannii ATCC 19606. Compared with wild-type LPS, outer membrane vesicles and inactivated whole cells of engineered bacteria had a statistically significant decreased ability to produce IL-6. Structural analysis of lipid A by negative-ion matrix-assisted laser desorption/ionization time-of-ﬂight mass spectrometry revealed that the profile of lipid A fractions under PagL expression was changed. Taken together, our data showed that recombinant penta-acylated lipid A had less immunoreactivity and that the tetra-acylated version of lipid A with TLR4 antagonist activity decreased the induction of IL-6 production in the murine macrophage cell line J774 A.1.
authors: Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
authors: Farzad
authors: F
authors: Badmasti
authors: Fereshteh
authors: F
authors: Shahcheraghi
authors: Seyed Davar
authors: SD
authors: Siadat
authors: Saeid
authors: S
authors: Bouzari
authors: Soheila
authors: S
authors: Ajdary
authors: Mohsen
authors: M
authors: Amin
authors: Raheleh
authors: R
authors: Halabian
authors: Abbas Ali
authors: AA
authors: Imani Fooladi
mesh_terms: D040981:Acinetobacter baumannii / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018274:Electroporation; D004731:Endotoxins / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D015870:Gene Expression; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014169:Transformation, Bacterial
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D002265:Carboxylic Ester Hydrolases