Effects of subinhibitory concentrations of menthol on adaptation, morphological, and gene expression changes in enterohemorrhagic Escherichia coli.
Menthol (C(10)H(20)O) possesses antibacterial activity; nevertheless, bacterial adaptation to this compound has never been studied. Here we report that precultivation of enterohemorrhagic Escherichia coli (EHEC) strains in increasing subinhibitory (SI) concentrations of menthol significantly elevates (4- to 16-fold) their resistance to menthol. Concomitant morphological alterations included the appearance of mucoid colonies and reduced biofilm production. Scanning electron microscopy (SEM) examination revealed suppressed curli formation in menthol-adapted cells. Expression of the gene cpsB10 (encoding one of the enzymes responsible for colanic acid production) was elevated in response to SI concentrations of menthol in a laboratory E. coli strain, whereas expression in an rcsC null mutant was reduced, implicating a partial role for the Rcs phosphorelay system in mediating the menthol signal. Adaptation to menthol also reduced expression of the locus of enterocyte effacement-encoded regulator (Ler). This reduction, together with reduced curli and biofilm formation and elevated mucoidity, suggests a general reduction in bacterial virulence following adaptation to menthol. Our results thus suggest menthol as a potential lead in the recently emerging alternative strategy of targeting bacterial virulence factors to develop new types of anti-infective agents.
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Elad
E
Landau
Roni
R
Shapira
D000220:Adaptation, Biological / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000235:genetics / Q000502:physiology*; D054324:Enterohemorrhagic Escherichia coli / Q000187:drug effects* / Q000472:pathogenicity / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000502:physiology; D049452:Green Fluorescent Proteins; D008610:Menthol / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D014774:Virulence; D001616:beta-Galactosidase
D049452:Green Fluorescent Proteins; D008610:Menthol; D001616:beta-Galactosidase