Evaluation of risedronate as an antibiofilm agent.
Escherichia coli cra null mutants have been reported in the literature to be impaired in biofilm formation. To develop E. coli biofilm-inhibiting agents for prevention and control of adherent behaviour, analogues of a natural Cra ligand, fructose-1,6-bisphosphate, were identified based on two-dimensional similarity to the natural ligand. Of the analogues identified, those belonging to the bisphosphonate class of drug molecules were selected for study, as these are approved for clinical use in humans and their safety has been established. Computational and in vitro studies with purified Cra protein showed that risedronate sodium interacted with residues in the fructose-1,6-bisphosphate-binding site. Using a quantitative biofilm assay, risedronate sodium, at a concentration of 300-400 μM, was found to decrease E. coli and Salmonella pullorum biofilm formation by >60 %. Risedronate drastically reduced the adherence of E. coli cells to a rubber Foley urinary catheter, demonstrating its utility in preventing the formation of biofilm communities on medical implant surfaces. The use of risedronate, either alone or in combination with other agents, to prevent the formation of biofilms on surfaces is a novel finding that can easily be translated into practical applications.
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Shamlan M S
SMS
Reshamwala
Department of Electrical Engineering, Indian Institute of Technology Bombay, Mumbai, India.
Chandrasekhar
C
Mamidipally
Molecular Simulations Group, Department of Pharmaceutical Chemistry, Goa College of Pharmacy, , Panaji, India.
Raghuvir R S
RRS
Pissurlenkar
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, , Mumbai, India.
Evans C
EC
Coutinho
Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India.
Santosh B
SB
Noronha
D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects*; D005635:Fructosediphosphates / Q000737:chemistry; D017353:Gene Deletion; D012097:Repressor Proteins / Q000378:metabolism; D000068296:Risedronic Acid / Q000494:pharmacology*; D012475:Salmonella / Q000187:drug effects; D014546:Urinary Catheterization; D056968:Lac Repressors
D001426:Bacterial Proteins; D005635:Fructosediphosphates; D012097:Repressor Proteins; D000068296:Risedronic Acid; C068837:FruR protein, Bacteria; D056968:Lac Repressors; C029063:fructose-1,6-diphosphate