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 β-lactamase bla TEM-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-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 μg/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.
Institute of Clinical Medicine, Schsool of Medicine, National Yang-Ming University Taipei, Taiwan ; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes Taipei, Taiwan ; Division of Infectious Diseases, Taipei Veterans General Hospital Taipei, Taiwan.
Shu-Chen
SC
Kuo
Institute of Clinical Medicine, Schsool of Medicine, National Yang-Ming University Taipei, Taiwan ; Emergency Department, Taipei Veterans General Hospital Taipei, Taiwan.
Yi-Tzu
YT
Lee
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes Taipei, Taiwan.
Tsai-Ling
TL
Yang Lauderdale
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes Taipei, Taiwan.
Wei-Cheng
WC
Huang
Division of Infectious Diseases, Taipei Veterans General Hospital Taipei, Taiwan.
Ming-Fen
MF
Chuang
Division of Infectious Diseases, Taipei Veterans General Hospital Taipei, Taiwan.
Chien-Pei
CP
Chen
Department of Internal Medicine, Mackay Memorial Hospital Hsin-Chu, Taiwan.
Shey-Chiang
SC
Su
Department of Molecular Medicine and Institute of Life Science, National Tsing Hua University Hsin-Chu, Taiwan.
Kuan-Rong
KR
Lee
Institute of Clinical Medicine, Schsool of Medicine, National Yang-Ming University Taipei, Taiwan ; Division of Infectious Diseases, Taipei Veterans General Hospital Taipei, Taiwan.
Te-Li
TL
Chen
Acinetobacter baumannii; Acinetobacter-derived cephalosporinase (ADC); mechanisms of resistance; sulbactam; transformation