Abstract
Active efflux is regarded as a common mechanism for antibiotic and biocide resistance. However, the role of many drug efflux pumps in biocide resistance in Acinetobacter baumannii remains unknown. Using biocide-resistant A. baumannii clinical isolates, we investigated the incidence of 11 known/putative antimicrobial resistance efflux pump genes (adeB, adeG, adeJ, adeT1, adeT2, amvA, abeD, abeM, qacE, qacEΔ1, and aceI) and triclosan target gene fabI through PCR and DNA sequencing. Reverse transcriptase quantitative PCR was conducted to assess the correlation between the efflux pump gene expression and the reduced susceptibility to triclosan or chlorhexidine. The A. baumannii isolates displayed high levels of reduced susceptibility to triclosan, chlorhexidine, benzalkonium, hydrogen peroxide, and ethanol. Most tested isolates were resistant to multiple antibiotics. Efflux resistance genes were widely distributed and generally expressed in A. baumannii. Although no clear relation was established between efflux pump gene expression and antibiotic resistance or reduced biocide susceptibility, triclosan non-susceptible isolates displayed relatively increased expression of adeB and adeJ whereas chlorhexidine non-susceptible isolates had increased abeM and fabI gene expression. Increased expression of adeJ and abeM was also demonstrated in multiple antibiotic resistant isolates. Exposure of isolates to subinhibitory concentrations of triclosan or chlorhexidine induced gene expression of adeB, adeG, adeJ and fabI, and adeB, respectively. A point mutation in FabI, Gly95Ser, was observed in only one triclosan-resistant isolate. Multiple sequence types with the major clone complex, CC92, were identified in high level triclosan-resistant isolates. Overall, this study showed the high prevalence of antibiotic and biocide resistance as well as the complexity of intertwined resistance mechanisms in clinical isolates of A. baumannii, which highlights the importance of antimicrobial stewardship and resistance surveillance in clinics.
Highlights
Acinetobacter baumannii is an important human nosocomial pathogen which causes a variety of infections, including bacteremia, pneumonia, meningitis, septicemia, urinary tract infections, wound and skin infections (Bergogne-Berezin and Towner, 1996; Peleg et al, 2008; La Forgia et al, 2010)
The results revealed the role of several efflux pumps in chlorhexidine or triclosan resistance and the complexity of biocide resistance mechanisms, which highlight the importance for antimicrobial stewardship including the use of biocide agents
Antimicrobial resistance in A. baumannii is a major threat for the successful treatment and control of infections (Peleg et al, 2008; Ling, 2010)
Summary
Acinetobacter baumannii is an important human nosocomial pathogen which causes a variety of infections, including bacteremia, pneumonia, meningitis, septicemia, urinary tract infections, wound and skin infections (Bergogne-Berezin and Towner, 1996; Peleg et al, 2008; La Forgia et al, 2010). A. baumannii is a major threat to human health, has the ability to persist and colonize various environments and displays multiple drug resistance to antimicrobial agents such as antibiotics and biocides (Bergogne-Berezin and Towner, 1996; Babaei et al, 2015; Chang et al, 2015). Reduced susceptibility to biocides among bacterial species, including A. baumannii, has been increasingly observed in patients in recent years (Peleg and Paterson, 2006; Gnanadhas et al, 2013; Babaei et al, 2015; Fernández-Cuenca et al, 2015). Crossresistance between biocide exposure and antibiotic resistance (and vice versa) in bacteria has been recently reported (Curiao et al, 2015; Fernández-Cuenca et al, 2015). The molecular characterization of reduced biocide susceptibility and its relationship with antibiotic resistance in A. baumannii remains to be fully determined
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