Disruption of biofilms and killing of Burkholderia cenocepacia from cystic fibrosis lung using an antioxidant-antibiotic combination therapy.

Autor: Aiyer A; Department of Infectious Diseases and Immunology, Charles Perkins Centre, School of Medical Sciences, The University of Sydney. Electronic address: aditi.aiyer@sydney.edu.au., Manoharan A; Department of Infectious Diseases and Immunology, Charles Perkins Centre, School of Medical Sciences, The University of Sydney. Electronic address: manoharan.arthika@sydney.edu.au., Paino D; Department of Infectious Diseases and Immunology, Charles Perkins Centre, School of Medical Sciences, The University of Sydney. Electronic address: dpai8675@uni.sydney.edu.au., Farrell J; Department of Infectious Diseases and Immunology, School of Medical Sciences, The University of Sydney and Whiteley Corporation, Level 5, 12 Mount Street North Sydney NSW 2060. Electronic address: jessica.farrell@sydney.edu.au., Whiteley GS; Whiteley Corporation, Level 5, 12 Mount Street North Sydney NSW 2060. Electronic address: greg.whiteley@whiteley.com.au., Kriel FH; Whiteley Corporation, 19-23 Laverick Avenue, Tomago NSW 2322. Electronic address: erik@whiteley.com.au., Glasbey TO; Whiteley Corporation, 19-23 Laverick Avenue, Tomago NSW 2322. Electronic address: trevor@whiteley.com.au., Manos J; Department of Infectious Diseases and Immunology, Charles Perkins Centre, School of Medical Sciences, The University of Sydney. Electronic address: jim.manos@sydney.edu.au., Das T; Department of Infectious Diseases and Immunology, Charles Perkins Centre, School of Medical Sciences, The University of Sydney. Electronic address: das.ashishkumar@sydney.edu.au.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2021 Aug; Vol. 58 (2), pp. 106372. Date of Electronic Publication: 2021 Jun 08.
DOI: 10.1016/j.ijantimicag.2021.106372
Abstrakt: Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The resulting chloride and bicarbonate imbalance produces a thick, static lung mucus. This mucus is not easily expelled from the lung and can be colonised by bacteria, leading to biofilm formation. CF lung infection with Burkholderia cepacia complex (BCC), particularly the subspecies B. cenocepacia, results in higher morbidity and mortality. Patients infected with BCC can rapidly progress to "cepacia syndrome", a fatal necrotising pneumonia. The aim of this study was to identify whether a combination therapy (CT) of selected antioxidants and antibiotics significantly disrupts B. cenocepacia biofilms and to determine the optimum CT level for treatment. Using controlled in vitro spectrophotometry, colony-forming unit and microscopy assays, three antioxidants (N-acetylcysteine [NAC], glutathione and vitamin C) and three antibiotics (ciprofloxacin, ceftazidime and tobramycin) were screened and assessed for their ability to disrupt the early and mature biofilms of six B. cenocepacia CF isolates. A combination of NAC and ciprofloxacin produced a statistically significant biofilm disruption in all strains tested, with growth inhibition (>5-8 log 10 ) observed when exposed to 4890 or 8150 μg/mL NAC in combination with 32 or 64 μg/mL ciprofloxacin. NAC-mediated biofilm disruption may be aided by the acidic pH of NAC at higher concentrations. This study showed that NAC is an effective disruptor that reduces the necessity for high concentrations of antibiotic. Further research will focus on the host toxicity and efficacy in ex vivo CF models.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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