Exposure to trace levels of live seaweed-derived antibacterial 2,4,6-tribromophenol modulates β-lactam antibiotics resistance in Vibrio

Non-antibiotic substances have been found to contribute to the spread of antibiotic resistance. Bromophenols (BPs) are special anti-bacterial substances obtained from seaweed. This study explored the modulatory effect of trace BPs from a live seaweed on the antibiotic resistance of pathogenic Vibrio (V.) strains. A hydroponic solution of Ulva fasciata was found to contain trace levels (9–333 μg L−1) of 2,4,6-tribromophenol (TBP), a typical BP. TBP at a concentration of 165 μg L−1 significantly increased the inhibition zone diameter of widely used β-lactam antibiotics (amoxicillin and ampicillin) against V. alginolyticus M7 (Va. M7) and V. parahaemolyticus M3 (Vp. M3) as well as reduced the minimum inhibitory concentration by 2–4 fold against Va. M7. Whole genome re-sequencing analysis demonstrated that Va. M3 (53−60) had more mutant genes than Vp. M7 (44) in β-lactam resistance pathway. Transcriptome sequencing analysis, along with verification through RT-qPCR, further showed that oligopeptide permease (opp) was the only differentially expressed gene (DEG) among the mutated genes in the β-lactam resistance pathway. The opp transport activity and membrane permeability of Vibrio were both enhanced at 165 μg L−1 of TBP, and the ability of biofilm formation was also decreased. Thus, antibiotics resistance improvement of Vibrio by TBP was potentially related with the promoted opp transport activity, membrane permeability and inhibited biofilm formation.