title: Inhibition of bacterial adhesion by sub-inhibitory concentrations: brodimoprim vs trimethoprim.
abstract: There is accumulating evidence that sub-inhibitory concentrations (sub-MICs) of many antibiotics are not without effect on bacteria and even though they do not kill bacteria, they are still able to interfere with some important aspects of bacterial cell function. The aim of the present study was to investigate the effect of sub-MICs of brodimoprim and trimethoprim on Escherichia coli and Staphylococcus aureus adhesiveness to human mucosal cells. Sub-MICs of brodimoprim down to 1/32 MIC (0.03 microgram/ml) significantly reduced the E. coli adhesion to human buccal epithelial cells and this inhibition was significantly higher than the corresponding pattern for trimethoprim. Adhesion of S. aureus was significantly reduced down to 1/16 MIC for both brodimoprim and trimethoprim but no significant differences resulted between the two patterns. 2,4 Diaminopyrimidines and related structures have a high affinity for the enzyme dihydrofolate reductase and this causes a reduction in the synthesis of essential purines, thus reducing also DNA and the synthesis or expression of surface adhesins.
authors.affiliation: Dept. of Pharmacology, School of Medicine, University of Milan, Italy.
authors.forename: P C
authors.initials: PC
authors.lastname: Braga
authors.forename: G
authors.initials: G
authors.lastname: Piatti
authors.forename: A
authors.initials: A
authors.lastname: Limoli
authors.forename: M
authors.initials: M
authors.lastname: Santoro
authors.forename: T
authors.initials: T
authors.lastname: Gazzola
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005493:Folic Acid Antagonists; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D005493:Folic Acid Antagonists; D014295:Trimethoprim; C037079:brodimoprim