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| Status |
Public on May 14, 2024 |
| Title |
The coordinated adaptation of Staphylococcus aureus to calprotectin dependent metal sequestration [RNA-Seq] |
| Organism |
Staphylococcus aureus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The host protein calprotectin inhibits the growth of a variety of bacterial pathogens through metal sequestration in a process known as 'nutritional immunity'. Staphylococcus aureus growth is inhibited by calprotectin in vitro and calprotectin is localized in vivo to staphylococcal abscesses during infection. However, the staphylococcal adaptations that provide defense against nutritional immunity and the role of metal-responsive regulators are not fully characterized. In this work, we define the transcriptional response of S. aureus and the role of the metal-responsive regulators, Zur, Fur, and MntR, in response to metal limitation by calprotectin exposure. Additionally, we identified genes affecting the fitness of S. aureus during metal limitation through a Transposon sequencing (Tn-seq) approach. Loss of function mutations in clpP, which encodes a proteolytic subunit of the ATP-dependent Clp protease, demonstrate reduced fitness of S. aureus to the presence of calprotectin. ClpP contributes to pathogenesis in vivo in a calprotectin-dependent manner. These studies establish a critical role for ClpP to combat metal limitation by calprotectin and reveal the genes required for S. aureus to outcompete the host for metals.
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| Overall design |
To study the response of S. aureus to nutrient metal limitation by treatment with CP, a global transcriptomic analysis by RNA-seq was performed on a wild-type (WT) S. aureus strain, or metal-sensing regulator mutants (Fur, Zur, MntR) grown in media with either WT calprotectin (WTCP) which restricts bacteria from Zn, Fe, Mn, Cu, and Ni, or a His6 site mutant calprotectin (∆s1CP) that only restricts Zn and Cu. A vehicle control using CP buffer and TSB was used.
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| Contributor(s) |
Reyes Ruiz VM, Freiberg JA, Weiss A, Green ER, Jobson M, Felton E, Shaw LN, Chazin WJ, Skaar EP |
| Citation(s) |
38920392 |
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| Submission date |
Apr 26, 2024 |
| Last update date |
Aug 09, 2024 |
| Contact name |
Eric P Skaar |
| Organization name |
Vanderbilt University Medical Center
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| Department |
Pathology, Microbiology, and Immunology
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| Lab |
Eric Skaar
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| Street address |
1161 21st Avenue South
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| City |
Nashville |
| State/province |
Tennessee |
| ZIP/Postal code |
37232 |
| Country |
USA |
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| Platforms (1) |
| GPL27158 |
Illumina NovaSeq 6000 (Staphylococcus aureus) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA1105033 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE265954_RNAseq_Mastersheet_4635_VR.xlsx |
1.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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