The Albicidin Resistance Factor AlbD Is a Serine Endopeptidase That Hydrolyzes Unusual Oligoaromatic-Type Peptides.

Abstract

The para-aminobenzoic acid-containing peptide albicidin is a pathogenicity factor synthesized by Xanthomonas albilineans in infections of sugar cane. Albicidin is a nanomolar inhibitor of the bacterial DNA gyrase with a strong activity against various Gram-negative bacteria. The bacterium Pantoea dispersa expresses the hydrolase AlbD, conferring natural resistance against albicidin. We show that AlbD is a novel type of endopeptidase that catalyzes the cleavage of albicidin at a peptide backbone amide bond, thus abolishing its antimicrobial activity. Additionally, we determined the minimal cleavage motif of AlbD with substrates derived by chemical synthesis. Our results clearly identify AlbD as a unique endopeptidase that is the first member of a new subfamily of peptidases. Our findings provide the molecular basis for a natural detoxification mechanism, potentially rendering a new tool in biological chemistry approaches.

• Authors: Laura Vieweg, Julian Kretz, Alexander Pesic, Dennis Kerwat, Stefan Grätz, Monique Royer, Stéphane Cociancich, Andi Mainz, Roderich D Süssmuth
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 137 Issue 24 Pg. 7608-11 (Jun 24 2015) ISSN: 1520-5126 [Electronic] United States
• PMID: 26057615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Organic Chemicals
• albicidin
• Serine Endopeptidases
• serine endopeptidase

Topics

• Anti-Bacterial Agents (metabolism, pharmacology)
• Drug Resistance, Bacterial
• Enterobacteriaceae Infections (drug therapy, microbiology)
• Humans
• Hydrolysis
• Organic Chemicals (metabolism, pharmacology)
• Pantoea (drug effects, enzymology)
• Serine Endopeptidases (metabolism)
• Xanthomonas (metabolism)