Cystic fibrosis (CF) is a disease caused by mutations in the CF transmembrane conductance regulator. The resulting chloride and bicarbonate imbalance produces a thick static lung mucus. This mucus is not easily expelled from the lungs, and so can be colonised by bacteria, leading to biofilm formation. CF lung infection with Burkholderia cepacia complex (BCC), especially the subspecies B. cenocepacia, results in higher morbidity and mortality. Patients infected with BCC can rapidly progress to “cepacia syndrome”, a fatal necrotising pneumonia. We aimed to identify whether a combination therapy (CT) of selected antioxidants and antibiotics significantly disrupts B. cenocepacia biofilms and 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) 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. Our study demonstrated 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.
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