title: Salmonella enterica serovar Typhimurium bla(PER-1)-carrying plasmid pSTI1 encodes an extended-spectrum aminoglycoside 6'-N-acetyltransferase of type Ib.
abstract: 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.
authors.affiliation: Service de Microbiologie, Hôpital Saint-Louis, INSERM EMI-U 0004-LRMA, Université Paris VI, France. isabelle.casin@sls.ap-hop-paris.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Casin
authors.forename: Beatrice
authors.initials: B
authors.lastname: Hanau-Berçot
authors.forename: Isabelle
authors.initials: I
authors.lastname: Podglajen
authors.forename: Haluk
authors.initials: H
authors.lastname: Vahaboglu
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Collatz
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D010957:Plasmids / Q000235:genetics*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C056532:aminoglycoside N(6')-acetyltransferase