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| Status |
Public on Oct 23, 2008 |
| Title |
Transcriptional profiles of Staphylococcus aureus strains in the presence of the lantibiotic mersacidin. |
| Platform organism |
Staphylococcus aureus subsp. aureus N315 |
| Sample organism |
Staphylococcus aureus |
| Experiment type |
Expression profiling by array
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| Summary |
The lantibiotic mersacidin is an antimicrobial peptide of 20 amino acids that is ribosomally produced by Bacillus sp. strain HIL Y-85,54728. Mersacidin acts by complexing the sugar phosphate head group of the peptidoglycan precursor lipid II, thereby inhibiting the transglycosylation reaction of peptidoglycan biosynthesis.
Here, we studied the transcriptomic response of S. aureus to subinhibitory concentrations of mersacidin using microarray and qRT-PCR techniques. The transcriptomics revealed an extensive induction of the cell wall stress response of S. aureus, which is partly controlled by the two-component regulatory system VraSR. In contrast to other cell wall-active antibiotics such as vancomycin, 0.2 x MIC of mersacidin was sufficient for induction. Interestingly, the cell wall stress response was equally induced in vancomycin intermediate resistant S. aureus (VISA) as well as in a highly susceptible strain. Furthermore, the efficiency of mersacidin was not affected by an increased cell wall thickness, which is part of the VISA-type resistance mechanism. Since the transcription of the VraDE ABC transporter genes was induced up to 1700-fold in our experiments, we analyzed the role of VraDE in the response of S. aureus to mersacidin. Unexpectedly, the deletion of the vraE gene did not result in an increased susceptibility to mersacidin compared to the wild type strain. In conclusion, mersacidin appears to be a strong inducer of the cell wall stress response of S. aureus at very low concentrations, which reflects its general mode of action as a cell wall-active peptide as well as its use of a unique target site on lipid II.
Keywords: antibiotic induced response
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| Overall design |
In this experiment, the transcriptomic response of S. aureus was assayed via microarray analysis.
To this end, S. aureus strains SA137/93A [mersacidin MIC 35 mg/L] and SA137/93G [mersacidin MIC 30 mg/L] were grown without or with mersacidin [16 mg/L] to determine the genes being induced or repressed by the lantibiotic. SA137/93G was additionally grown in the presence of 4 mg/L mersacidin. Furthermore, the highly susceptible S. aureus strain SG511 [mersacidin MIC 1 mg/L] was also grown without or with mersacidin [1 mg/L].
Each experiment was performed 4 times including a dye swap resulting in four chips per competitive comparison to increase reproducibility. Only strain SA137/93G incubated with 0.2 x MIC of mersacidin was reproduced in duplicate. All hybridizations were done with equal amounts of cDNA probes displaying similar picomoles of incorporated dye.
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| Contributor(s) |
Sass P |
| Citation(s) |
18947397 |
| |
| Submission date |
Oct 08, 2007 |
| Last update date |
Mar 17, 2012 |
| Contact name |
Peter Sass |
| E-mail(s) |
[email protected]
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| Organization name |
University of Bonn
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| Department |
Institute for Microbiology (IMMIP)
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| Street address |
Sigmund-Freud-Straße 25
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| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
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| Platforms (2) |
| GPL5421 |
sciTracer Staphylococcus aureus N315 Scienion2005 |
| GPL5429 |
sciTracer Staphylococcus aureus N315 Scienion2004 |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA102887 |
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