Various Evolutionary Trajectories Lead to Loss of the Tobramycin-Potentiating Activity of the Quorum-Sensing Inhibitor Baicalin Hydrate in Burkholderia cenocepacia Biofilms

• DOI: 10.1128/aac.02092-18
• Publication Date: 2019-01-23T15:06:15Z
• Authors: Andrea Sass; Lisa Slachmuylders; Heleen Van Acker; Ian Vandenbussche; Lisa Ostyn; Mona Bové; Aurélie Crabbé; Laurent R. Chiarelli; Silvia Buroni; Filip Van Nieuwer...; Emmanuel Abatih; Tom Coenye
• Keywords: Burkholderia cenocepacia; Baicalin; Burkholderia cepacia complex

Combining antibiotics with potentiators that increase their activity is a promising strategy to tackle infections caused by antibiotic-resistant bacteria. As do not interfere essential processes, it has been hypothesized they are less likely induce resistance. However, evidence supporting this hypothesis lacking. In the present study, we investigated whether Burkholderia cenocepacia J2315 biofilms develop reduced susceptibility toward one such adjuvant, baicalin hydrate (BH). Biofilms were repeatedly and intermittently treated tobramycin (TOB) alone or in combination BH for 24 h. After treatment, remaining cells quantified using plate counting. 15 cycles, biofilm susceptible TOB TOB+BH compared start population, potentiating effect of was lost. Whole-genome sequencing performed probe which changes involved BH, mutations 14 protein-coding genes identified (including central metabolism BCAL0296, encoding an ABC transporter). No MIC MBC number persister observed. basal intracellular levels reactive oxygen species (ROS) ROS found after treatment markedly decreased evolved populations. addition, cultures significantly uptake Our results indicate B. rapidly lose antibiotic-potentiating point metabolism, production, as mechanisms.