|
| Status |
Public on Jul 01, 2010 |
| Title |
Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence |
| Organism |
Staphylococcus aureus |
| Experiment type |
Expression profiling by array
|
| Summary |
Staphylococcus aureus is a major human pathogen and resistant to numerous clinically used antibiotics. The first antibiotic developed for S. aureus infections was the nonribosomal petide secondary metabolite penicillin. We discovered cryptic nonribosomal peptide secondary metabolites, the aureusimines, made by S. aureus itself that are not antibiotics, but function as small molecule regulators of virulence factor expression. Using established rules and codes for nonribosomal peptide assembly we predicted these nonribosomal peptides, and used these predictions to identify them from S. aureus culture broths. Functional studies using global microarray and mouse bacteremia models established that the aureusimines control virulence factor expression and are necessary for productive infections. This is the first report of the aureusimines and has important implications for the treatment of drug resistant S. aureus. Targeting aureusimine synthesis may provide novel anti-infectives.
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| |
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| Overall design |
Commerically available S. aureus GeneChips (Affymetrix) were used to compare biological replicates of early and late exponential phase wild type (Newman) and aureusimine defective (ausA) organisms.
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| |
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| Contributor(s) |
Wyatt AM, Wang W, Roux CM, Beasley F, Heinrichs DE, Dunman PM, Magarvey NA |
| Citation(s) |
20522739 |
| |
| Submission date |
Apr 16, 2010 |
| Last update date |
Oct 18, 2012 |
| Contact name |
Paul M Dunman |
| E-mail(s) |
[email protected]
|
| Phone |
402 559-7745
|
| Fax |
402 559-4077
|
| URL |
http://dunmanlab.com
|
| Organization name |
University of Nebraska Medical Center
|
| Department |
Pathology and Microbiology
|
| Street address |
986495 Nebraska Medical Center
|
| City |
Omaha |
| State/province |
NE |
| ZIP/Postal code |
68198-6495 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL1339 |
[S_aureus] Affymetrix S. aureus Genome Array |
|
| Samples (8)
|
| GSM533913 |
Newman early exponential replicate 1 |
| GSM533914 |
Newman early exponential replicate 2 |
| GSM533915 |
Newman (ausA) early exponential replicate 1 |
| GSM533916 |
Newman (ausA) early exponential replicate 2 |
| GSM533917 |
Newman late exponential replicate 1 |
| GSM533918 |
Newman late exponential replicate 2 |
| GSM533919 |
Newman (ausA) late exponential replicate 1 |
| GSM533920 |
Newman (ausA) late exponential replicate 2 |
|
| Relations |
| BioProject |
PRJNA126083 |
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