title: Alkali-earth metal bridges formed in biofilm matrices regulate the uptake of fluoroquinolone antibiotics and protect against bacterial apoptosis.
abstract: 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.
authors.affiliation: Institute of Organic Contaminant Control and Soil Remediation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Jiangsu 210095, China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Jiangsu 210008, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Organic Contaminant Control and Soil Remediation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Jiangsu 210095, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Shou
authors.affiliation: Soil Research Centre, University of Reading, Whiteknights, Reading RG6 6DW, UK.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Collins
authors.affiliation: Institute of Organic Contaminant Control and Soil Remediation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Jiangsu 210095, China. Electronic address: gaoyanzheng@njau.edu.cn.
authors.forename: Yanzheng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects*; D001673:Biodegradation, Environmental / Q000187:drug effects; D018441:Biofilms; D002939:Ciprofloxacin / Q000378:metabolism / Q000493:pharmacokinetics; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D024841:Fluoroquinolones / Q000378:metabolism* / Q000493:pharmacokinetics; D008672:Metals, Alkali / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D008672:Metals, Alkali; D002939:Ciprofloxacin
keywords: Alkali–earth metals; Biofilms; Bridging energy; Computational chemistry; Escherichia coli; Fluoroquinolone antibiotics