PXD044054

PXD044054 is an original dataset announced via ProteomeXchange.

Title	Lethal Antibiotic Exposure Drives the Convergent Evolution of High Tolerance Phenotype Conferred by nfxB Mutation in clinically relevant Pseudomonas aeruginosa
Description	Fluoroquinolone antibiotics, a common antibiotic for the treatment of Pseudomonas aeruginosa infection, are facing challenges due to the rapid evolution of bacterial resistance. Through designed evolutionary experiments in vitro, we find that there are significant differences in evolutionary trajectories and outcomes of resistant bacteria obtained in different induction modes, among which fitness benefit of resistant strains obtained in high-dose induction mode under high level of antibiotic is significantly higher than that of wild-type strain, and collateral sensitivity to aminoglycosides and some other antibiotics will be obtained. Resistance strains obtained in the low-dose induction mode exhibit higher heterogeneity, which is accompanied by multiple drug resistance (MDR). Through second generation resequencing and proteomic techniques, overexpression of MexCD-OprJ efflux pump induced by mutations in the nfxB gene significantly improved the fitness benefit of Pseudomonas aeruginosa PAO1 under high level of fluoroquinolones. This is the precondition of the further evolution of the fleroxacin-resistant strains in the high dose induction mode, the addition of the efflux pump inhibitor phenylalanyl arginyl β-naphthylamide (PAβN) could effectively repress the evolution of bacterial resistance in the high dose induction mode. Fleroxacin use followed by gentamicin helped drive infectious P.aeruginosa to extinction, causing nfxB mutation to cause collateral sensitivity to gentamicin.
HostingRepository	PRIDE
AnnounceDate	2025-02-15
AnnouncementXML	Submission_2025-02-14_23:16:59.626.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	hanzhong feng
SpeciesList	scientific name: Pseudomonas aeruginosa; NCBI TaxID: 287;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-24 19:34:27	ID requested
⏵ 1	2025-02-14 23:17:00	announced

Dataset with its publication pending

submitter keyword: antibiotic,Pseudomonas aeruginosa,resistance

Yomngxing He
contact affiliation	Lanzhou University, Lanzhou, Gansu, China
contact email	heyx@lzu.edu.cn
lab head
hanzhong feng
contact affiliation	Lanzhou University
contact email	fenghzh19@lzu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044054
     1. Label: PRIDE project
     2. Name: Lethal Antibiotic Exposure Drives the Convergent Evolution of High Tolerance Phenotype Conferred by nfxB Mutation in clinically relevant Pseudomonas aeruginosa