Small-Molecule Modulators of Listeria monocytogenes Biofilm Development
| Autor: | Lori L. Burrows, Uyen Nguyen, Iwona B. Wenderska, Matthew A. Chong, Kalinka Koteva, Gerard D. Wright |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.drug_class
Microbial Sensitivity Tests medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Palmitic acid Structure-Activity Relationship chemistry.chemical_compound Listeria monocytogenes Sphingosine medicine Enzyme Inhibitors Protein kinase C Ecology biology Fatty Acids Palmitoylcarnitine Biofilm Protein kinase inhibitor biology.organism_classification Small molecule Anti-Bacterial Agents Biochemistry chemistry Biofilms Food Microbiology Listeria Protein Kinases Bacteria Food Science Biotechnology |
| Zdroj: | Applied and Environmental Microbiology. 78:1454-1465 |
| ISSN: | 1098-5336 0099-2240 |
| Popis: | Listeria monocytogenes is an important food-borne pathogen whose ability to form disinfectant-tolerant biofilms on a variety of surfaces presents a food safety challenge for manufacturers of ready-to-eat products. We developed here a high-throughput biofilm assay for L. monocytogenes and, as a proof of principle, used it to screen an 80-compound protein kinase inhibitor library to identify molecules that perturb biofilm development. The screen yielded molecules toxic to multiple strains of Listeria at micromolar concentrations, as well as molecules that decreased (≤50% of vehicle control) or increased (≥200%) biofilm formation in a dose-dependent manner without affecting planktonic cell density. Toxic molecules—including the protein kinase C antagonist sphingosine—had antibiofilm activity at sub-MIC concentrations. Structure-activity studies of the biofilm inhibitory compound palmitoyl- d,l -carnitine showed that while Listeria biofilm formation was inhibited with a 50% inhibitory concentration of 5.85 ± 0.24 μM, d,l -carnitine had no effect, whereas palmitic acid had stimulatory effects. Saturated fatty acids between C 9:0 and C 14:0 were Listeria biofilm inhibitors, whereas fatty acids of C 16:0 or longer were stimulators, showing chain length specificity. De novo -synthesized short-chain acyl carnitines were less effective biofilm inhibitors than the palmitoyl forms. These molecules, whose activities against bacteria have not been previously established, are both useful probes of L. monocytogenes biology and promising leads for the further development of antibiofilm strategies. |
| Databáze: | OpenAIRE |
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