AUTHOR=Kuo Shu-Chen , Lee Yi-Tzu , Yang Lauderdale Tsai-Ling , Huang Wei-Cheng , Chuang Ming-Fen , Chen Chien-Pei , Su Shey-Chiang , Lee Kuan-Rong , Chen Te-Li 

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00231

DOI=10.3389/fmicb.2015.00231

ISSN=1664-302X

ABSTRACT=<p>The sulbactam resistance rate in <italic>Acinetobacter baumannii</italic> has increased worldwide. Previous reports have shown that the β-lactamase <italic>bla</italic><sub>TEM-1</sub> confers resistance to sulbactam in <italic>A. baumannii</italic>. The purpose of this study was to examine whether other β-lactamases, including the <italic>Acinetobacter</italic>-derived cephalosporinase (ADC), OXA-23, OXA-24/72, and OXA-58 families, also contribute to sulbactam resistance in <italic>A. baumannii</italic>. The correlation between these β-lactamases and the sulbactam minimal inhibitory concentration (MIC) was determined using <italic>A. baumannii</italic> 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 IS<italic>Aba1</italic>-<italic>bla</italic><sub>ADC-30</sub> 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 IS<italic>Aba1</italic>-<italic>bla</italic><sub>ADC-30</sub> into susceptible strains increased the sulbactam MIC from 2 to 32 μg/ml, which required <italic>bla</italic><sub>ADC-30</sub> overexpression using an upstream promoter in IS<italic>Aba1</italic>. 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 <italic>bla</italic><sub>ADC-30</sub> 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 <italic>A. baumannii</italic> isolates.</p>