PXD067190

PXD067190 is an original dataset announced via ProteomeXchange.

Title	Upregulation of the AcrAB2NodT efflux pump confers antibiotic resistance at the cost of collateral metal sensitivity
Description	Bacterial resistance to antibiotics (AB) such as β-lactams, fluoroquinolones, and aminoglycosides often emerges through mutations that alter AB targets, reduce membrane permeability, or increase the activity of AB-modifying enzymes and efflux pumps. Yet the physiological costs associated with AB resistance remain poorly understood. In Caulobacter vibrioides, a ∆tipR mutant that which constitutively upregulates the RND pump AcrAB2nodT, displays heightened sensitivity to copper (Cu), revealing a physiological vulnerability driven by the energetic burden imposed by excessive efflux activity. Deletion of acrAB2nodT in the ∆tipR background restored Cu resistance to wild-type levels, confirming the role of pump overexpression in metal sensitivity. Morphological and microscopy analyses revealed that pump overexpression leads to cell envelope defects and compromised fitness. To disentangle the effects of pump abundance from efflux activity, we engineered an AcrB2 transport-impaired mutant. This variant also rescued Cu resistance, demonstrating that high expression and active transport contribute to the observed toxicity. Notably, this sensitivity was not limited to Cu; the ∆tipR mutant also exhibited increased susceptibility to other transition metals, including zinc (Zn), nickel (Ni) and cadmium (Cd), suggesting a broader vulnerability linked to metal stress. Mechanistically, pump overexpression depleted the proton motive force, reduced ATP levels, and impaired motility, all of which are essential for Cu stress adaptation. This physiological tradeoff highlights the importance of precise efflux regulation and reveals a potential therapeutic vulnerability: targeting the cost of pump upregulation could enhance the efficacy of antimicrobial treatments.
HostingRepository	PRIDE
AnnounceDate	2026-03-02
AnnouncementXML	Submission_2026-03-01_18:12:56.338.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD067190
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marc Dieu
SpeciesList	scientific name: Caulobacter vibrioides; NCBI TaxID: NEWT:155892;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-11 04:25:01	ID requested
⏵ 1	2026-03-01 18:12:57	announced

10.1038/s42003-026-09606-x;

10.6019/PXD067190;

Ote M, Lardinois L, Hendrickx E, Dieu M, Jur, ė, nas D, Matroule JY, NodT overexpression links antibiotic resistance to metal sensitivity in Caulobacter vibrioides. Commun Biol, 9(1):(2026) [pubmed]

submitter keyword: Antibiotics, heavy metals, metal sensitivity, stress response, Caulobacter, efflux pumps, antibiotic resistance, copper

Jean-Yves Matroule
contact affiliation	Research Unit in Biology of Microorganisms (URBM), Department of Biology, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium.
contact email	jean-yves.matroule@unamur.be
lab head
Marc Dieu
contact affiliation	University of Namur - MaSUN
contact email	marc.dieu@unamur.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067190
     1. Label: PRIDE project
     2. Name: Upregulation of the AcrAB2NodT efflux pump confers antibiotic resistance at the cost of collateral metal sensitivity