Heterologous Expression of 3-O-Deacylase in Acinetobacter baumannii Modulates the Endotoxicity of Lipopolysaccharide

被引:5
作者
Badmasti, Farzad [1 ]
Shahcheraghi, Fereshteh [1 ]
Siadat, Seyed Davar [1 ]
Bouzari, Saeid [2 ]
Ajdary, Soheila [3 ]
Amin, Mohsen [5 ]
Halabian, Raheleh [4 ]
Fooladi, Abbas Ali Imani [4 ]
机构
[1] Baqiyatallah Univ Med Sci, Dept Bacteriol, Tehran, Iran
[2] Baqiyatallah Univ Med Sci, Dept Mol Biol, Tehran, Iran
[3] Baqiyatallah Univ Med Sci, Pasteur Inst Iran, Dept Immunol, Tehran, Iran
[4] Baqiyatallah Univ Med Sci, Appl Microbiol Res Ctr, Tehran, Iran
[5] Univ Tehran Med Sci, Fac Pharm, Dept Drug & Food Control, Tehran, Iran
关键词
Acinetobacter baumannii ATCC 19606; 3-O-deacylase enzyme; Lipopolysaccharide; Lipid A; Endotoxicity; Outer membrane vesicle; Inactivated whole cell; TOLL-LIKE RECEPTOR-4; PSEUDOMONAS-AERUGINOSA; MODIFYING ENZYMES; PAGL; LPS; PERTUSSIS; VACCINE;
D O I
10.1159/000371815
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
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. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:37 / 44
页数:8
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