PXD034987-1

PXD034987 is an original dataset announced via ProteomeXchange.

Title	The proteomic responses of carbapenemase-producing and non-producing carbapenem-resistant Pseudomonas aeruginosa strains to subminimal-inhibitory concentrations of meropenem revealed by quantitative tandem mass spectrometry
Description	Pseudomonas aeruginosa is a major opportunistic pathogen causing a wide range of infections and one of the most problematic bacteria regarding antibiotic resistance, with an increasing incidence of multidrug and extensively-drug resistant strains, including resistance to last resource antibiotics such as carbapenems. Resistances are often due to complex interplays of naturally and acquired resistance mechanisms which are enhanced by its remarkably large regulatory network. Thus, the use of non-targeted shotgun methodologies such as mass spectrometry-based proteomics is crucial to understand these interplays and to reveal possible strain and species-specific novel mechanisms of antibiotic resistance. The aim of this study was to determine the proteomic response of two carbapenem-resistant and extensively-drug-resistant P. aeruginosa strains to subminimal inhibitory concentrations (sub-MICs) of meropenem. The strains belonged to high-risk clones ST235 and ST395, one carrying a class 1 integron-encoded VIM-4 metallo-β-lactamase and one carrying no acquired antibiotic resistance genes. Each strain was cultivated with three different sub-MICs of meropenem, and a quantitative shotgun proteomic approach was applied, using tandem mass tag (TMT) isobaric labeling followed by nano-liquid chromatography tandem-mass spectrometry, to determine significantly up- or down-regulated proteins and enriched groups of proteins and pathways. Cultivation of both strains with ½ and ¼ of the MIC, resulted in hundreds of differentially regulated proteins, including several β-lactamases, transport-related proteins (including multiple porins and efflux pumps), proteins associated with peptidoglycan metabolism and cell wall organization and dozens of regulatory proteins. Remarkably, all components of the H1 type VI secretion system were up-regulated in one of the strains. Enrichment analyses revealed that multiple metabolic pathways were affected. Additionally, numerous proteins of unknown function were also differentially-regulated in each strain. In conclusion, high subminimal-inhibitory concentrations of meropenem cause massive changes in the proteomes of carbapenem-resistant P. aeruginosa strains, involving a wide range of common and strain-specific mechanisms and proteins, many still uncharacterized which might potentially play a role in the susceptibility of P. aeruginosa to meropenem.
HostingRepository	PRIDE
AnnounceDate	2023-01-05
AnnouncementXML	Submission_2023-01-05_05:53:10.256.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JohannesFuchs
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-30 02:57:14	ID requested
⏵ 1	2023-01-05 05:53:10	announced

Dataset with its publication pending

submitter keyword: multidrug resistance, high-risk clones, opportunistic pathogen,antibiotic resistance, tandem mass spectrometry, tandem mass tag (TMT), quantitative proteomics, carbapenem, Pseudomonas aeruginosa, meropenem, antimicrobial resistance, LC-MS/MS

RogerKarlsson
contact affiliation	Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden
contact email	roger.karlsson@vgregion.se
lab head
JohannesFuchs
contact affiliation	Gothenburg University
contact email	johannes.fuchs@gu.se
dataset submitter

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/2023/01/PXD034987

PRIDE project URI

• PRIDE
  1. PXD034987
     1. Label: PRIDE project
     2. Name: The proteomic responses of carbapenemase-producing and non-producing carbapenem-resistant Pseudomonas aeruginosa strains to subminimal-inhibitory concentrations of meropenem revealed by quantitative tandem mass spectrometry