Alkali–earth metal bridges formed in biofilm matrices regulate the uptake of fluoroquinolone antibiotics and protect against bacterial apoptosis

Bacterially extracellular biofilms play a critical role in relieving toxicity of fluoroquinolone antibiotic (FQA) pollutants, yet it is unclear whether antibiotic attack may be defused by a bacterial one-two punch strategy associated with metal-reinforced detoxification efficiency. Our findings help to assign functions to specific structural features of biofilms, as they strongly imply a molecularly regulated mechanism by which freely accessed alkali–earth metals in natural waters affect the cellular uptake of FQAs at the water-biofilm interface. Specifically, formation of alkali-earth-metal (Ca2+ or Mg2+) bridge between modeling ciprofloxacin and biofilms of Escherichia coli regulates the trans-biofilm transport rate of FQAs towards cells (135-nm-thick biofilm). As the addition of Ca2+ and Mg2+ (0–3.5 mmol/L, CIP: 1.25 μmol/L), the transport rates were reduced to 52.4% and 63.0%, respectively. Computational chemistry analysis further demonstrated a deprotonated carboxyl in the tryptophan residues of biofilms acted as a major bridge site, of which one side is a metal and the other is a metal girder jointly connected to the carboxyl and carbonyl of a FQA. The bacterial growth rate depends on the bridging energy at anchoring site, which underlines the environmental importance of metal bridge formed in biofilm matrices in bacterially antibiotic resistance. [Display omitted] •Weak interactions at the molecular level are quantitatively associated with a macroscopically biological effect.•Metal bridge formed in extracellular biofilms acts through a suppressive trans-biofilm transport to protect bacterial cells.•Bacterial growth rate depends on the bridging energy at the anchoring site. Alkali–earth metal bridges formed in biofilm matrices regulate the uptake of fluoroquinolone antibiotics and protect against bacterial apoptosis.