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| Status |
Public on Jul 31, 2024 |
| Title |
Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection |
| Organism |
Staphylococcus aureus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S. aureus from initial and chronic infections. We observed upregulated collagenase and proline transporter gene expression in chronic infection isolates. Metabolomics of bronchiolar lavage fluid, fibroblast infection, growth assays and analysis of bacterial mutant strains showed that airway fibroblasts produce collagen during S. aureus infection. Host-adapted bacteria upregulate collagenase, which degrades collagen and releases proline. S. aureus then imports proline, which fuels oxidative metabolism via the tricarboxylic acid cycle. Proline metabolism provides host-adapted S. aureus with a metabolic benefit enabling out-competition of non-adapted strains. These data suggest that clinical settings characterized by airway repair processes and fibrosis provide a milieu that promotes S. aureus adaptation and supports infection.
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| Overall design |
S. aureus was grown to OD1 in LB plus/minus 100uM proline. RNA was extracted and DNAse treatment performed. RNA was sent for sequencing.
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Azenta Life Sciences
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| Contributor(s) |
Urso A, Prince A |
| Citation missing |
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| Submission date |
May 29, 2024 |
| Last update date |
Jul 31, 2024 |
| Contact name |
ALICE PRINCE |
| E-mail(s) |
ASP7@cumc.columbia.edu
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| Organization name |
COLUMBIA UNIVERSITY
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| Department |
PEDIATRICS ID
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| Lab |
PRINCE LAB
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| Street address |
650 W 168TH ST
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| City |
NEW YORK |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL26273 |
Illumina HiSeq 3000 (Staphylococcus aureus) |
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| Samples (8)
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| GSM8295808 |
bacteria, OD1, subculture,WT-Proline R2 |
| GSM8295809 |
bacteria, OD1, subculture, ADSA R1 |
| GSM8295810 |
bacteria, OD1, subculture, ADSA R2 |
| GSM8295811 |
bacteria, OD1, subculture, adsa-Proline R1 |
| GSM8295812 |
bacteria, OD1, subculture, adsa-Proline R2 |
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| Relations |
| BioProject |
PRJNA1117949 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE268637_Differential_expression_analysis_table_A_VS_B.csv.gz |
157.3 Kb |
(ftp)(http) |
CSV |
| GSE268637_Differential_expression_analysis_table_A_VS_C.csv.gz |
48.1 Kb |
(ftp)(http) |
CSV |
| GSE268637_Differential_expression_analysis_table_B_VS_D.csv.gz |
50.5 Kb |
(ftp)(http) |
CSV |
| GSE268637_Differential_expression_analysis_table_C_VS_D.csv.gz |
167.9 Kb |
(ftp)(http) |
CSV |
| GSE268637_RAW.tar |
20.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
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