Exogenous maltose enhances Zebrafish immunity to levofloxacin‐resistant Vibrio alginolyticus

Understanding the interplay between bacterial fitness, antibiotic resistance, host immunity and host metabolism could guide treatment and improve immunity against antibiotic‐resistant pathogens. The acquisition of levofloxacin (Lev) resistance affects the fitness of Vibrio alginolyticus in vitro and in vivo. Lev‐resistant (Lev‐R) V. alginolyticus exhibits slow growth, reduced pathogenicity and greater resistance to killing by the host, Danio rerio (zebrafish), than Lev‐sensitive (Lev‐S) V. alginolyticus, suggesting that Lev‐R V. alginolyticus triggers a weaker innate immune response in D. rerio than Lev‐S V. alginolyticus. Differences were detected in the metabolome of D. rerio infected with Lev‐S or Lev‐R V. alginolyticus. Maltose, a crucial metabolite, is significantly downregulated in D. rerio infected with Lev‐R V. alginolyticus, and exogenous maltose enhances the immune response of D. rerio to Lev‐R V. alginolyticus, leading to better clearance of the infection. Furthermore, we demonstrate that exogenous maltose stimulates the host production of lysozyme and its binding to Lev‐R V. alginolyticus, which depends on bacterial membrane potential. We suggest that exogenous exposure to crucial metabolites could be an effective strategy for treating and/or managing infections with antibiotic‐resistant bacteria.