Structural heterogeneity regarding local Shwartzman activity of lipid A.
The relation of chemical structure to local Shwartzman activity of lipid A preparations purified by thin-layer chromatography from five bacterial strains was examined. Two lipid A fractions from E. coli F515--Ec-A2 and Ec-A3--exhibited strong activity, similar to that of previous synthetic E. coli-type lipid A (compound 506 or LA-15-PP). The Ec-A3 fraction contained a component that appeared to be structurally identical to compound 506, and the main component of Ec-A2 fraction was structurally similar to compound 506 except that it carried a 3-hydroxytetradecanoyl group at the C-3' position of the backbone in place of a 3-tetradecanoyloxytetradecanoyl group. Free lipid A (12 C) and purified lipid A fractions, Ec-A2 (12 C) and Ec-A3 (12 C), respectively, obtained from bacteria grown at 12 C, exhibited activity comparable to Ec-A2 or Ec-A3. In these preparations, a large part of the 3-dodecanoyloxytetradecanoyl group might be replaced by 3-hexadecenoyloxytetradecanoyl group. Salmonella minnesota R595 free lipid A also contained at least two active lipid A components as seen in E. coli lipid A, but the third component corresponding to the synthetic Salmonella-type lipid A (compound 516 or LA-16-PP) exhibited low activity. A lipid A fraction, Cv-A4 from Chromobacterium violaceum IFO 12614, which was proposed to have two acyloxyacyl groups at the C-2 and C-2' positions with other acyl groups, exhibited weaker activity than the free lipid A or LPS. The purified lipid A fractions from Pseudomonas diminuta JCM 2788 and Pseudomonas vesicularis JCM 1477 contained an unusual backbone with 2,3-diamino-2,3-dideoxy-D-glucose disaccharide phosphomonoester, and these lipid A (Pd-A3 and Pv-A3) exhibited strong activity comparable to the E. coli lipid A. Thus, the present results show that the local Shwartzman reaction can be expressed by partly different lipid A structures in both hydrophilic backbone and fatty acyl residues; when they have the same backbone the potency varies markedly depending on the structure of the acyl residues.
Mashimo
J
J
Department of Microbial Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo.
Tanaka
C
C
Arata
S
S
Akiyama
Y
Y
Hata
S
S
Hirayama
T
T
Egawa
K
K
Kasai
N
N
D000818:Animals; D002861:Chromobacterium / Q000032:analysis; D004926:Escherichia coli / Q000032:analysis; D005260:Female; D008050:Lipid A / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D011549:Pseudomonas / Q000032:analysis; D011817:Rabbits; D012475:Salmonella / Q000032:analysis; D012790:Shwartzman Phenomenon / Q000209:etiology*; D013329:Structure-Activity Relationship
D008050:Lipid A