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
Article first published online: 12 SEP 2012
© 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 113, Issue 5, pages 1273–1286, November 2012
How to Cite
Knudsen, G.M., Holch, A. and Gram, L. (2012), 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. Journal of Applied Microbiology, 113: 1273–1286. doi: 10.1111/j.1365-2672.2012.05435.x
- Issue published online: 17 OCT 2012
- Article first published online: 12 SEP 2012
- Accepted manuscript online: 24 AUG 2012 12:08AM EST
- Manuscript Accepted: 15 AUG 2012
- Manuscript Revised: 14 AUG 2012
- Manuscript Received: 9 MAY 2012
- Danish Council for Independent Research, Technology and Production Sciences (FTP). Grant Number: 09-066098 274-08-0531
- gene expression;
- Listeria monocytogenes ;
- stress response;
- subinhibitory antibiotic concentrations;
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.
Methods and 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.
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 σB-dependent gene expression.
Significance and Impact of the Study
Although subinhibitory concentrations of antibiotics affect gene expression in L. monocytogenes, the changes did not increase virulence but did enhance the acid sensitivity.