PXD018372 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Stress response within the host affects antibiotic persistence and treatment outcome in Staphylococcus aureus infections |
Description | Staphylococcus aureus can cause severe invasive infections that require prolonged antibiotic treatment. Although S. aureus can easily acquire antibiotic resistance, even fully susceptible bacteria can persist and survive antibiotic therapy, thus complicating treatment. These so-called persisters are phenotypic variants of bacteria characterized by an arrested-growth phenotype that can tolerate high concentrations of chemotherapeutics and are associated with chronic and recurrent infections. Here, we show that S. aureus recovered directly from infection sites, displayed an increased bacterial lag-phase heterogeneity, forming more non-stable small colonies, indicating the presence of dormant bacteria. Infection modelling showed that host-mediated stress, including acidic pH, neutrophil exposure and murine abscesses, as well as antibiotic treatment, promoted formation of persisters both in vitro and in vivo. Proteomics and RNA-sequencing revealed molecular changes in bacteria in response to acidic stress leading to an overall more virulent population. However, after persister-enrichment, S. aureus displayed downregulation of pathways involved in virulence, cell division, and DNA replication, while ribosomal proteins, nucleotide-, and amino acid- metabolic pathways were upregulated, suggesting their requirement to fuel and maintain the persister phenotype. We demonstrate that decreased aconitase activity and ATP-levels as well as accumulation of insoluble proteins correlated with dormancy and growth reactivation cycles. Combination of antibiotics with retinoid derivatives, especially CD1530, significantly reduced both persisters and total bacterial load in a murine infection model. Our study provides an in-depth characterization of S. aureus persisters and shows that treatment failure due to antibiotic persistence could be addressed by using retinoid derivatives in combination with conventional antibiotics. |
HostingRepository | PRIDE |
AnnounceDate | 2021-09-09 |
AnnouncementXML | Submission_2021-09-09_01:01:37.193.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD018372 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Thomas Bock |
SpeciesList | scientific name: Staphylococcus aureus; NCBI TaxID: 1280; |
ModificationList | Oxidation; Acetyl; monohydroxylated residue; acetylated residue; Carbamidomethyl; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-04-04 10:17:45 | ID requested | |
⏵ 1 | 2021-09-09 01:01:39 | announced | |
Publication List
Huemer M, Mairpady Shambat S, Bergada-Pijuan J, S, ö, derholm S, Boumasmoud M, Vulin C, G, ó, mez-Mejia A, Antelo Varela M, Tripathi V, G, ö, tschi S, Marques Maggio E, Hasse B, Brugger SD, Bumann D, Schuepbach RA, Zinkernagel AS, lead to high antibiotic persistence and affect therapy success. Proc Natl Acad Sci U S A, 118(7):(2021) [pubmed] |
Keyword List
submitter keyword: Antibiotic Persistence |
Contact List
Alexander Schmidt |
contact affiliation | University of Basel, Biozentrum, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland, Tel. +41 61 207 2059 |
contact email | alex.schmidt@unibas.ch |
lab head | |
Thomas Bock |
contact affiliation | Proteomics Core Facility, Biozentrum, University of Basel, Switzerland |
contact email | thomas.bock@unibas.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD018372 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018372
- Label: PRIDE project
- Name: Stress response within the host affects antibiotic persistence and treatment outcome in Staphylococcus aureus infections