In:
Journal of Bacteriology, American Society for Microbiology, Vol. 188, No. 12 ( 2006-06-15), p. 4531-4541
Abstract:
Modification of the phosphate groups of lipid A with amine-containing substituents, such as phosphoethanolamine, reduces the overall net negative charge of gram-negative bacterial lipopolysaccharide, thereby lowering its affinity to cationic antimicrobial peptides. Modification of the 1 position of Helicobacter pylori lipid A is a two-step process involving the removal of the 1-phosphate group by a lipid A phosphatase, LpxE HP (Hp0021), followed by the addition of a phosphoethanolamine residue catalyzed by EptA HP (Hp0022). To demonstrate the importance of modifying the 1 position of H. pylori lipid A, we generated LpxE HP -deficient mutants in various H. pylori strains by insertion of a chloramphenicol resistance cassette into lpxE HP and examined the significance of LpxE with respect to cationic antimicrobial peptide resistance. Using both mass spectrometry analysis and an in vitro assay system, we showed that the loss of LpxE HP activity in various H. pylori strains resulted in the loss of modification of the 1 position of H. pylori lipid A, thus confirming the function of LpxE HP . Due to its unique lipid A structure, H. pylori is highly resistant to the antimicrobial peptide polymyxin (MIC 〉 250 μg/ml). However, disruption of lpxE HP in H. pylori results in a dramatic decrease in polymyxin resistance (MIC, 10 μg/ml). In conclusion, we have characterized the first gram-negative LpxE-deficient mutant and have shown the importance of modifying the 1 position of H. pylori lipid A for resistance to polymyxin.
Type of Medium:
Online Resource
ISSN:
0021-9193
,
1098-5530
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2006
detail.hit.zdb_id:
1481988-0
SSG:
12
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