Abstract
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.
Highlights
Acinetobacter baumannii causes various nosocomial infections, and the prevalence of multidrug-resistant (MDR) A. baumannii has been increasing in different countries
Association of Selected β-Lactamases with Sulbactam Resistance in A. baumannii A. baumannii clinical isolates were randomly selected from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, which contains 1640 Acinetobacter isolates collected from 2002 to 2010 (Kuo et al, 2012)
In addition to TEM-1(Krizova et al, 2013), ISAba1-blaADC−30 may play a role in providing A. baumannii with sulbactam resistance
Summary
Acinetobacter baumannii causes various nosocomial infections, and the prevalence of multidrug-resistant (MDR) A. baumannii has been increasing in different countries. This bacterium has intrinsic resistance to multiple drugs and can gain resistance mechanisms from other species (Peleg et al, 2008). The SENTRY program documented non-susceptibility to carbapenems, the last resort of drugs for the treatment of MDR A. baumannii, increased from 34.5% in 2006 to 59.8% in 2009 worldwide (Gales et al, 2011). Combination therapies or new drugs such as antimicrobial peptides or silver nanoparticles have been proposed as novel modalities to treat MDR A. baumannii (Peleg et al, 2008; Tiwari et al, 2014)
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