Muropeptides in Pseudomonas aeruginosa and their Role as Elicitors of β-Lactam-Antibiotic Resistance.
Muropeptides are a group of bacterial natural products generated from the cell wall in the course of its turnover. These compounds are cell-wall recycling intermediates and are also involved in signaling within the bacterium. However, the identity of these signaling molecules remains elusive. The identification and characterization of 20 muropeptides from Pseudomonas aeruginosa is described. The least abundant of these metabolites is present at 100 and the most abundant at 55,000 molecules per bacterium. Analysis of these muropeptides under conditions of induction of resistance to a β-lactam antibiotic identified two signaling muropeptides (N-acetylglucosamine-1,6-anhydro-N-acetylmuramyl pentapeptide and 1,6-anhydro-N-acetylmuramyl pentapeptide). Authentic synthetic samples of these metabolites were shown to activate expression of β-lactamase in the absence of any β-lactam antibiotic, thus indicating that they serve as chemical signals in this complex biochemical pathway.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Mijoon
M
Lee
Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
Supurna
S
Dhar
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Stefania
S
De Benedetti
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Dusan
D
Hesek
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Bill
B
Boggess
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Blas
B
Blázquez
Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA. matheek@fiu.edu.
Kalai
K
Mathee
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA. mobashery@nd.edu.
Shahriar
S
Mobashery
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000187:drug effects*; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010455:Peptides; D047090:beta-Lactams; D001618:beta-Lactamases
antibiotic resistance; bacteria; muropeptides; peptidoglycan; β-lactamase