Synergistic Activity of OligoG with Anti-Gram-Negative Antibiotics against Pseudomonas aeruginosa and Burkholderia spp.

Background. Burkholderia cepacia (BC), Burkholderia multivorans (BV) and Pseudomonas aeruginosa (PSA) represent a major problem in the colonization and infection of the lungs of patients with cystic fibrosis (CF). OligoG, an alginate subunit, disrupts biofilms and therefore is a candidate molecule for treating CF patients. Here, we test OligoG against a range of Pseudomonas and Burkholderia spp. with conventional anti-Gram-negative antibiotics. Methods. Fourteen multi-resistant non-clonal BC, BV and PSA were tested against azithromycin (AZM), erythromycin (ERM), clarithromycin (CLR), ciprofloxacin (CIP), gentamicin (GEN), amikacin (AMK), aztreonam (AZT), ceftazidime (CTZ) and imipenem (IMP) with three concentrations of OligoG (2%, 6%, 10%). Disruption of bacterial biofilms by OligoG therapy was also assessed. The effect of OligoG on PSA and BC biofilms was studied using confocal laser scanning microscopy (CLSM); employing live/dead staining or BODIPY® 630/650-X, SE and FM®1-43 (Invitrogen) labelling. Results. MICs with 10% OligoG reduced the MIC values 8-64 fold for AZT, 8-64 fold for IMP, 832-fold for CTZ, 4-8-fold for AZM, 2-8-fold for ERM with BC and BV strains. For PSA, the greatest synergy was seen with AZM (4-32 fold decrease), ERM (2-16 fold decrease), CLR (2-16 fold decrease) CTZ (2-16 fold decrease) and (2-8 fold decrease). The effects with 6% OligoG were similar, but less pronounced. No change in the tetracycline MICs were observed and minor antagonism was seen with aminoglycosides. The addition of 6% and 10% OligoG decreased the PSA and BC biofilms by approx. 80%.