Frontiers in Microbiology (Mar 2015)

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

  • Shu-Chen eKuo,
  • Yi-Tzu eLee,
  • Tsai-Ling eYang Lauderdale,
  • Wei-Cheng eHuang,
  • Ming-Fen eChuang,
  • Chien-Pei eChen,
  • Shey-Chiang eSu,
  • Kuan-Rong eLee,
  • Te-Li eChen,
  • Te-Li eChen

DOI
https://doi.org/10.3389/fmicb.2015.00231
Journal volume & issue
Vol. 6

Abstract

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The sulbactam resistance rate in Acinetobacter baumannii has increased worldwide. Previous reports have shown that the β-lactamase blaTEM-1 confers resistance to sulbactam in A. baumannii. The purpose of this study was to examine whether other β-lactamases including, the Acinetobacter-derived cephalosporinase (ADC), OXA-23, OXA-24/72, and OXA-58 families, also contribute to sulbactam resistance in A. baumannii. The correlation between these β-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-blaADC-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-blaADC-30 into susceptible strains increased the sulbactam MIC from 2 to 32 μg/ml, which required blaADC-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 blaADC-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.

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