Bacteria modify the negative approach

Abstract

Lipid A constitutes much of the outer lipid coat of disease-causing Gram negative organisms such as Escherichia coli, Salmonella and Pseudomonas. A novel method of bacterial resistance has been identified, by which an unusual sugar, aminoarabinose, is attached to the lipid, with the overall effect of reducing the net negative charge of the bacterial coat. Antibiotics (e.g. polymyxin) attach to the bacterial lipid coat via positively charged groups, the interactions of which are lessened with weakened negativity of the aminoarabinose-coated lipid. Duke University Medical Center biochemist Christian Raetz (Durham, NC, USA) said, ‘… we have discovered the enzyme that attaches this modifying group to lipid A, as well as a novel precursor molecule (named undecaprenyl phosphate-aminoarabinose) that donates this aminoarabinose to lipid A. It might be possible to redesign peptide antibiotics to work even against bacteria with aminoarabinose attached to their lipid A. … Also, one could imagine devising inhibitors of our aminoarabinose transferase enzyme that would render polymyxin resistant mutants sensitive again.’ The transferase enzyme was pinpointed by genetically analysing a polymyxin-resistant strain of Salmonella (the arnT gene codes for the protein responsible for transferring aminoarabinose to lipid A). A similar gene to arnT has been identified in resistant strains of E. coli. In future studies, the scientists will trace the full metabolic pathway, which could yield additional enzyme targets for inhibitory drugs. These findings are being published in the Journal of Biological Chemistry. S de B (http://www.jbc.org/http://www.eurekalert.org/pub_releases/2001-09/du-hbh091801.php)