PXD018372

PXD018372 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-04 10:17:45	ID requested
⏵ 1	2021-09-09 01:01:39	announced

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]

submitter keyword: Antibiotic Persistence

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

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PRIDE project URI

• PRIDE
  1. PXD018372
     1. Label: PRIDE project
     2. Name: Stress response within the host affects antibiotic persistence and treatment outcome in Staphylococcus aureus infections