title: Changes in antimicrobial susceptibility in a population of Salmonella enterica serovar Dublin isolated from cattle in Japan from 1976 to 2005.
abstract: OBJECTIVE
  We investigated the antimicrobial susceptibilities and resistance mechanisms of cattle-adapted Salmonella enterica serovar Dublin isolated in Japan in the past 30 years. This study is an example of evaluation of the impact of introduction of antimicrobials in veterinary medical practice on the selection of resistance in S. enterica.
  
  
  METHODS
  The antimicrobial susceptibilities and prevalence of R-plasmids in Salmonella Dublin isolated in Japan from 1976 to 2005 were investigated. To evaluate the importance of gyrA mutation and active efflux, we derived the gyrA revertants and acrAB deletion mutants, and then compared with their parental strains the MICs of quinolone antimicrobials such as nalidixic acid, enrofloxacin, ofloxacin and ciprofloxacin.
  
  
  RESULTS
  Salmonella Dublin isolates with R-plasmids and resistance to more than three antimicrobials were predominant between 1981 and 1995. From the latter half of the 1990s to the present, Salmonella Dublin isolates without R-plasmids became dominant. The introduction of nalidixic acid into the veterinary field in the mid-1980s was followed by the emergence of nalidixic acid-resistant isolates, which are now predominant. We found only a single gyrA mutation (Asp-87-->Tyr) among the nalidixic acid-resistant isolates. Although the reduced susceptibilities to the fluoroquinolones were observed among the nalidixic acid-resistant isolates, none of the isolates was resistant to the fluoroquinolones used in this study. The MIC data for the fluoroquinolones differed up to 4-fold. Results of the susceptibility test using gyrA revertants and acrAB mutants suggest that the isolates with the gyrA mutation were selected by the use of nalidixic acid, and the AcrAB-TolC system accounts for the decreased fluoroquinolone susceptibilities.
  
  
  CONCLUSIONS
  These data suggest that the introduction of nalidixic acid in veterinary medicine seemed to affect the susceptibilities of Salmonella Dublin among the cattle population in Japan, whereas the introduction of enrofloxacin has not caused any additional effect. The prudent use of antimicrobials in the veterinary field should be continuously stressed.
authors.affiliation: Safety Research Team, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856, Japan. akiba@affrc.go.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Akiba
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakaoka
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Kida
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ishioka
authors.forename: Toshiya
authors.initials: T
authors.lastname: Sameshima
authors.forename: Noriyo
authors.initials: N
authors.lastname: Yoshii
authors.forename: Muneo
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Uchida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Terakado
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology* / Q000382:microbiology; D027081:DNA Gyrase / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D007564:Japan / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D015363:Quinolones / Q000494:pharmacology*; D011815:R Factors / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000453:epidemiology / Q000382:microbiology; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: C493251:AcrAB-TolC protein, Salmonella enterica; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015363:Quinolones; D027081:DNA Gyrase