AmpC cephalosporinase hyperproduction in Acinetobacter baumannii clinical strains

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Abstract
Objective: To compare the genetic environments of ampC genes in different Acinetobacter baumannii isolates showing different levels of β-lactam resistance. Methods: The patterns of β-lactam resistance and β-lactamase production were investigated for 42 A. baumannii clinical strains. The MICs of various β-lactams were determined in the presence or absence of the class C cephalosporinase inhibitor, cloxacillin (500 mg/L). The ampC gene and its 5′ adjacent sequence were analysed by PCR and DNA sequencing. An RT–PCR method was developed to evaluate ampC transcript levels. Results: Strains fell into three resistance groups: first, strains with a ceftazidime MIC ≤ 8 mg/L (20 strains, 47.6%); secondly, strains with a ceftazidime MIC 32 mg/L, which was reduced four-fold in the presence of cloxacillin (eight strains, 19%); and thirdly, strains with a ceftazidime MIC ≥ 256 mg/L, which did not decrease in the presence of cloxacillin (14 strains, 33.4%). In all of the resistant isolates (groups II and III), but not in any of the ceftazidime-susceptible isolates (group I), a 1180 bp insert showing all the characteristics of an insertion sequence was detected upstream from the ampC gene. Isolates having this insert overexpress ampC, according to RT–PCR experiments. Conclusion: Presence of an insertion sequence upstream of ampC in A. baumannii clinical isolates, possibly including a strong promoter, has the potential to cause over-expression of AmpC, resulting in high-level ceftazidime resistance.

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