Interference of sub-inhibitory concentrations of gatifloxacin on various determinants of bacterial virulence.
The physico-chemical characteristics of the molecular array on the outermost surface of bacteria modulate various bacterial functions which, when expressed in the human environment, constitute important determinants of bacterial virulence. The present study investigated the ability of subinhibitory concentrations of gatifloxacin to interfere with various virulence determinants of Escherichia coli and with the adhesiveness of Staphylococcus aureus. The adhesiveness of S. aureus and E. coli to human epithelial cells was inhibited at gatifloxacin concentrations down to 1/32 and 1/64 the minimum inhibitory concentration (MIC). Sub-MICs of gatifloxacin down to 1/8-MIC significantly reduced hemagglutination and hydrophobicity, which are correlated with fimbriation and provide clues relating to the physico-chemical characteristics of the outer surface of bacteria. Swarming (motility) was reduced at concentrations down to 1/8 MIC. Phagocytosis was not affected but killing significantly increased from 1/8 to 1/2 MIC. The respiratory bursts of neutrophils investigated by a chemiluminescence procedure were not modified. The interpolation of these pharmacodynamic findings with pharmacokinetic curves indicates that the effect of sub-MIC concentrations of gatifloxacin can engender activity, prolonging antimicrobial effects on virulence determinants over 30 hours after the antimicrobial concentration has fallen below the MIC.
Dal Sasso
M
M
Center of Respiratory Pharmacology, Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy.
Bovio
C
C
Culici
M
M
Braga
P C
PC
D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity*; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D010587:Phagocytosis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D014774:Virulence
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D000077734:Gatifloxacin