A periplasmic D-alanyl-D-alanine dipeptidase in the gram-negative bacterium Salmonella enterica.
The VanX protein is a D-alanyl-D-alanine (D-Ala-D-Ala) dipeptidase essential for resistance to the glycopeptide antibiotic vancomycin. While this enzymatic activity has been typically associated with vancomycin- and teicoplainin-resistant enterococci, we now report the identification of a D-Ala-D-Ala dipeptidase in the gram-negative species Salmonella enterica. The Salmonella enzyme is only 36% identical to VanX but exhibits a similar substrate specificity: it hydrolyzes D-Ala-D-Ala, DL-Ala-DL-Phe, and D-Ala-Gly but not the tripeptides D-Ala-D-Ala-D-Ala and DL-Ala-DL-Lys-Gly or the dipeptides L-Ala-L-Ala, N-acetyl-D-Ala-D-Ala, and L-Leu-Pro. The Salmonella dipeptidase gene, designated pcgL, appears to have been acquired by horizontal gene transfer because pcgL-hybridizing sequences were not detected in related bacterial species and the G+C content of the pcgL-containing region (41%) is much lower than the overall G+C content of the Salmonella chromosome (52%). In contrast to wild-type Salmonella, a pcgL mutant was unable to use D-Ala-D-Ala as a sole carbon source. The pcgL gene conferred D-Ala-D-Ala dipeptidase activity upon Escherichia coli K-12 but did not allow growth on D-Ala-D-Ala. The PcgL protein localizes to the periplasmic space of Salmonella, suggesting that this dipeptidase participates in peptidoglycan metabolism.
Hilbert
F
F
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
García-del Portillo
F
F
Groisman
E A
EA
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D001483:Base Sequence; D002460:Cell Line; D004269:DNA, Bacterial; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005798:Genes, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019897:Periplasm / Q000201:enzymology; D019779:Salmonella enterica / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D013347:Subcellular Fractions; D013379:Substrate Specificity; D014774:Virulence
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010450:Endopeptidases; D004150:Dipeptidases; C023381:pcgL protein, Salmonella