A periplasmic D-alanyl-D-alanine dipeptidase in the gram-negative bacterium Salmonella enterica

J Bacteriol. 1999 Apr;181(7):2158-65. doi: 10.1128/JB.181.7.2158-2165.1999.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins*
  • Base Sequence
  • Cell Line
  • DNA, Bacterial
  • Dipeptidases / genetics
  • Dipeptidases / metabolism
  • Dipeptidases / physiology*
  • Dogs
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Endopeptidases / physiology*
  • Genes, Bacterial
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Periplasm / enzymology
  • Salmonella enterica / enzymology*
  • Salmonella enterica / genetics
  • Salmonella enterica / pathogenicity
  • Subcellular Fractions
  • Substrate Specificity
  • Virulence

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • Endopeptidases
  • Dipeptidases
  • pcgL protein, Salmonella

Associated data

  • GENBANK/AF120672