New Antibiotics May Be Aimed at Membrane Carbohydrate Synthesis

Microbiologists have identified a gene cluster in the bacterium Burkholderia cenocepacia that controls synthesis of the key cell envelope component 4-amino-4-deoxy-L-arabinose (Ara4N). Cells lacking the enzymes for this complex carbohydrate demonstrate loss of viability associated with dramatic changes in bacterial cell morphology and ultrastructure, increased permeability to propidium iodide, and sensitivity to sodium dodecyl sulfate.

B cenocepacia is a Gram-negative bacterium that is common in the environment and may cause disease in plants. It is an opportunistic pathogen, and human infections are common in patients with cystic fibrosis and chronic granulomatous disease, and are often fatal.

Investigators at the University of Western Ontario (London, Ontario Canada) used a conditional mutagenesis strategy to demonstrate that a gene cluster encoding putative aminoarabinose (Ara4N) biosynthesis enzymes was essential for the viability of B cenocepacia. This finding was published in the May 2007 issue of the Journal of Bacteriology.

"We are very excited with these findings, as they will let us come up with novel molecules to disrupt the making of Ara4N,” said senior author Dr. Miguel Valvano, professor of microbiology and immunology at the University of Western Ontario. "These molecules could then be tested as novel antibiotics.”


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University of Western Ontario