PXD010305

PXD010305 is an original dataset announced via ProteomeXchange.

Title	Characterization of F. tularensis LVS outer membrane vesicles
Description	Francisella tularensis is a Gram-negative bacteria responsible for tularemia, a disease for which the high prevalence of failure and relapses is a main concern. Directed evolution experiments carried out in presence of antibiotics revealed that acquisition of fluoroquinolones (FQ) resistance was not exclusively related to mutations in DNA gyrase genes which are the first targets of these molecules. Here, using F. tularensis LVS as model, we investigated the role of FupA/B (Fer-Utilization Protein), whose possible contribution to FQ resistance was suggested by genomic analysis of resistant isolates. Using trans-complementation/mutagenesis approaches we definitely connected FupA/B expression to FQ sensitivity. Furthermore, we showed that the virulent strain F. tularensis subsp. tularensis SCHU S4, lacking the homologous FupA protein, exhibited a lower FQ susceptibility. Importantly, the deletion of this lipoprotein promoted an increased secretion of outer membrane vesicles (OMVs). Mass spectrometry-based quantitative proteomic characterization of OMVs from LVS and LVS-∆fupA/B strains led to the identification of 801 proteins among which a subset of 23 proteins exhibited a differential abundance between OMVs from both strains and may therefore contribute to the observed increased FQ susceptibility. We finally demonstrated that OMVs are structural key elements of F. tularensis LVS biofilms providing protection against FQ. Taken together, these results showed that mutations targeting FupA/B contribute to antimicrobial resistance through quantitative and qualitative modulations of OMV biogenesis and biofilm formation, providing new basis for understanding and fighting against Francisella antibiotic resistance and/or persistence.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:46:31.023.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yohann Couté
SpeciesList	scientific name: Francisella tularensis subsp. holarctica (strain LVS); NCBI TaxID: 376619;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-04 08:41:43	ID requested
1	2019-11-12 12:07:41	announced
⏵ 2	2024-10-22 04:46:31	announced	2024-10-22: Updated project metadata.

10.1080/22221751.2019.1615848;

Siebert C, Lindgren H, Ferr, é S, Villers C, Boisset S, Perard J, Sj, ö, stedt A, Maurin M, Brochier-Armanet C, Cout, é Y, Renesto P, : FupA mutation contributes to fluoroquinolone resistance by increasing vesicle secretion and biofilm formation. Emerg Microbes Infect, 8(1):808-822(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: fluoroquinolone, OMVs, tolerance,Francisella tularensis

Virginie Brun
contact affiliation	EDyP
contact email	virginie.brun@cea.fr
lab head
Yohann Couté
contact affiliation	EDyP
contact email	yohann.coute@cea.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010305
     1. Label: PRIDE project
     2. Name: Characterization of F. tularensis LVS outer membrane vesicles