Open AccessSalmonella enterica Serovar Typhimurium bla PER-1 -Carrying Plasmid pSTI1 Encodes an Extended-Spectrum Aminoglycoside 6′- N -Acetyltransferase of Type Ib
Author(s) -
I. Casin,
Béatrice Hanau-Berçot,
Isabelle Podglajen,
Haluk Vahaboğlu,
E. Collatz
Publication year - 2003
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.47.2.697-703.2003
Subject(s) - integron , acetyltransferase , biology , salmonella enterica , aminoglycoside , plasmid , gene , peptide sequence , nucleic acid sequence , open reading frame , chloramphenicol acetyltransferase , microbiology and biotechnology , genetics , escherichia coli , gene expression , reporter gene , antibiotics , acetylation
We have studied the aminoglycoside resistance gene, which confers high levels of resistance to both amikacin and gentamicin, that is carried by plasmid pSTI1 in the PER-1 beta-lactamase-producing strain of Salmonella enterica serovar Typhimurium previously isolated in Turkey. This gene, called aac(6')-Ib(11), was found in a class 1 integron and codes for a protein of 188 amino acids, a fusion product between the N-terminal moiety (8 amino acids) of the signal peptide of the beta-lactamase OXA-1 and the acetyltransferase. The gene lacked a plausible Shine-Dalgarno (SD) sequence and was located 45 nucleotides downstream from a small open reading frame, ORF-18, with a coding capacity of 18 amino acids and a properly spaced SD sequence likely to direct the initiation of aac(6')-Ib(11) translation. AAC(6')-Ib(11) had Leu118 and Ser119 as opposed to Gln and Leu or Gln and Ser, respectively, which were observed in all previously described enzymes of this type. We have evaluated the effect of Leu or Gln at position 118 by site-directed mutagenesis of aac(6')-Ib(11) and two other acetyltransferase gene variants, aac(6')-Ib(7) and -Ib(8), which naturally encode Gln118. Our results show that the combination of Leu118 and Ser119 confers an extended-spectrum aminoglycoside resistance, with the MICs of all aminoglycosides in clinical use, including gentamicin, being two to eight times higher for strains with Leu118 and Ser119 than for those with Gln118 and Ser119.