4-Amino-4-deoxy-L-arabinose in LPS of enterobacterial R-mutants and its possible role for their polymyxin reactivity.
The content of 4-amino-4-deoxy-L-arabinopyranose (L-Arap4N) and the phosphate substitution pattern of the LPS of various strains from Salmonella minnesota, Yersinia enterocolitica and Proteus mirabilis was determined by GC/MS, HPLC and 31P-NMR. These data allowed us to examine the possible role of these components for the polymyxin B-binding capacity of LPS and for the minimal inhibiting concentration (MIC) and the minimal bactericidal concentration (MBC) of polymyxins B and E towards the respective R-mutants. Contrary to other investigated Re-, Rd- and Rc-mutants of S. minnesota, strain R595 (Re-mutant) showed about a 90% substitution of the ester-linked phosphate-group with L-Arap4N, whereas the L-Arap4N content of the other S. minnesota strains amounted to 17-25%. Neither the binding capacity of LPS to polymyxin B, determined by a bioassay, nor the MIC- and MBC-values of the R-mutants were significantly affected by this alteration. Similar results were obtained after using the temperature-dependent changes in the L-Arap4N-content and phosphate substitution pattern of Y. enterocolitica 75R. In order to explore the relevant polymyxin B binding site, lipid A samples with or without substitution of their ester-linked phosphate group were prepared and subjected to the polymyxin-binding assay. The results obtained so far indicated that the inner core bound L-Arap4N, detected in all resistant strains investigated, may play a decisive role in the decreased binding of polymyxin B, responsible for the bacterial resistance towards polymyxin(s).
Boll
M
M
Max-Planck-Institut für Immunbiologie, Freiburg, FRG.
Radziejewska-Lebrecht
J
J
Warth
C
C
Krajewska-Pietrasik
D
D
Mayer
H
H
D000606:Amino Sugars / Q000032:analysis*; D004755:Enterobacteriaceae / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D008050:Lipid A / Q000031:analogs & derivatives / Q000737:chemistry / Q000235:genetics; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011113:Polymyxins / Q000378:metabolism / Q000494:pharmacology*; D013400:Sugar Acids / Q000737:chemistry
D000606:Amino Sugars; D008050:Lipid A; D008070:Lipopolysaccharides; D011113:Polymyxins; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate; C088602:3-deoxy-2-octulosonic acid(2)-lipid IV(A); C040134:4-amino-4-deoxyarabinose