Contribution of Acinetobacter-derived cephalosporinase-30 to sulbactam resistance in Acinetobacter baumannii

The sulbactam resistance rate in Acinetobacter baumannii has increased worldwide. Previous reports have shown that the beta-lactamase bla(TEM-1) confers resistance to sulbactam in A, baumannii. The purpose of this study was to examine whether other beta-lactamases, including the Acinetobacter-derived cephalosporinase (ADC), OXA-23, OXA-24/72, and OXA-58 families, also contribute to sulbactam resistance in A. baurnannii. The correlation between these beta-lactamases and the sulbactam minimal inhibitory concentration (MIC) was determined using A. baumannii clinical isolates from diverse clonality, which were collected in a nationwide surveillance program from 2002 to 2010 in Taiwan. A possible association between the genetic structure of ISAba1-bla(ADC-30) and sulbactam resistance was observed because this genetic structure was detected in 97% of sulbactam-resistant strains compared with 10% of sulbactam-susceptible strains. Transformation of ISAba1-bla(ADC-30) into susceptible strains increased the sulbactam MIC from 2 to 32 mu g/ml, which required bla(ADC-30) overexpression using an upstream promoter in ISAba1. Flow cytometry showed that ADC-30 production increased in response to sulbactam, ticarcillin, and ceftazidime treatment. This effect was regulated at the RNA level but not by an increase in the bla(ADC-30) gene copy number as indicated by quantitative PCR. Purified ADC-30 decreased the inhibitory zone created by sulbactam or ceftazidime, similarly to TEM-1. In conclusion, ADC-30 overexpression conferred resistance to sulbactam in diverse clinical A. baumannii isolates.