Mutations in the chloramphenicol acetyltransferase (S61G, Y105C) increase accumulated amounts and resistance in Pseudomonas aeruginosa

FEMS Microbiol Lett. 2004 Jul 15;236(2):197-204. doi: 10.1016/j.femsle.2004.05.037.

Abstract

A chloramphenicol acetyltransferase (catB7) gene containing two point mutations, 181A/G and 314A/G, has been recently reported to be a determinant for high-level chloramphenicol resistance phenotype in a Pseudomonas aeruginosa strain PAhcr1. The mutant CATB7 was further characterized in vitro and in vivo to elucidate the molecular basis of high-level resistance. CAT assay demonstrated that the mutant and wild-type recombinant CATB7 had similar specific activities. Dot blotting revealed that the accumulated amounts of CATB7 in P. aeruginosa strains PAO1 and PAhcr1 were proportionate to the respective anti-chloramphenicol level. Site-directed mutagenesis showed that G61S and Y105C contributed synergistically to the PAhcr1 resistance phenotype. It could be proposed that the mutant CATB7 was more structurally stable than catalytically efficient as a chloramphenicol resistance determinant in PAhcr1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Amino Acid Substitution
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Chloramphenicol / metabolism*
  • Chloramphenicol O-Acetyltransferase / chemistry
  • Chloramphenicol O-Acetyltransferase / genetics*
  • Chloramphenicol O-Acetyltransferase / isolation & purification
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Chloramphenicol Resistance / genetics*
  • Cloning, Molecular
  • Enzyme Stability
  • Genes, Bacterial
  • Microbial Sensitivity Tests
  • Mutagenesis, Site-Directed
  • Mutation*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / genetics*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • Chloramphenicol
  • Acetyl Coenzyme A
  • Chloramphenicol O-Acetyltransferase