title: Subinhibitory concentrations of antibiotics affect stress and virulence gene expression in Listeria monocytogenes and cause enhanced stress sensitivity but do not affect Caco-2 cell invasion.
abstract: OBJECTIVE
  Antibiotics can act as signal molecules and affect bacterial gene expression, physiology and virulence. The purpose of this study was to determine whether subinhibitory antibiotic concentrations alter gene expression and physiology of Listeria monocytogenes.
  
  
  RESULTS
  Using an agar-based screening assay with promoter fusions, 14 of 16 antibiotics induced or repressed expression of one or more stress and/or virulence genes. Despite ampicillin-induced up-regulation of PinlA-lacZ expression, Caco-2 cell invasion was not affected. Subinhibitory concentrations of ampicillin and tetracycline caused up- and down-regulation of stress response genes, respectively, but both antibiotics caused increased sensitivity to acid stress. Six combinations of gene-antibiotic were quantified in broth cultures and five of the six resulted in the same expression pattern as the agar-based assay.
  
  
  CONCLUSIONS
  Antibiotics affect virulence and/or stress gene expression; however, altered expression could not predict changes in phenotypic behaviour. Subinhibitory concentrations of antibiotics led to increased acid sensitivity, and we speculate that this is attributed to changes in cell envelope or reduced σ(B) -dependent gene expression.
  
  
  CONCLUSIONS
  Although subinhibitory concentrations of antibiotics affect gene expression in L. monocytogenes, the changes did not increase virulence but did enhance the acid sensitivity.
authors.affiliation: National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark. gmkn@food.dtu.dk
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: A
authors.initials: A
authors.lastname: Holch
authors.forename: L
authors.initials: L
authors.lastname: Gram
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D015536:Down-Regulation / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005798:Genes, Bacterial / Q000187:drug effects; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013312:Stress, Physiological; D013752:Tetracycline / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000667:Ampicillin; D013752:Tetracycline