PXD053955

PXD053955 is an original dataset announced via ProteomeXchange.

Title	The polyamino-isoprenyl enhancer NV716 potentializes the antibacterial activity of two families of multitarget inhibitors against the ESKAPEE bacterium Enterobacter cloacae, Part1bis (Enterobacter cloacae)
Description	The spread of antimicrobial resistance (AMR), coupled with the decline in antibiotic development, has become a major public health concern. Recent studies estimate that around 700,000 people die each year from infections caused by multidrug-resistant (MDR) bacteria. This led the WHO to publish the ESKAPEE list of high priority pathogens for AMR, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli. Among these, Gram-negative bacteria (K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., and E. coli) are particularly overrepresented. This is mainly due to their high propensity to develop multiple resistance mechanisms, in addition to their intrinsic resistance to many antimicrobials, which is due to their membrane composition and the expression of broad-spectrum efflux pumps. One strategy to combat such AMR is the use of drug enhancers that are able to restore the antibacterial activity of poorly active antibiotics. In this context, we demonstrated that the polyamino-isoprenyl enhancer, NV716, efficiently potentiates the antibacterial activity of two families of multi-target Ser/Cys-based enzyme inhibitors, namely the oxadiazolone derivatives (OX) and the Cyclipostins and Cyclophostin analogs (CyC), against Enterobacter cloacae, while remaining inactive against other Gram-negative bacteria. We confirmed that NV716 potentiates some OX & CyC compounds by permeabilizing the outer membrane and thus by increasing the inhibitor accumulation as shown by fluorescence confocal microscopy. By using bio-orthogonal click-chemistry activity-based protein profiling (CC-ABPP) approach coupled to proteomic analysis, we also identified the target proteins of the best OX & CyC inhibitors from E. cloacae lysate, thereby confirming their multi-target nature. Interestingly, 6 of the latter proteins were also captured via CC-ABPP in P. aeruginosa lysate, and are highly conserved in all Gram-negative bacteria. These results provide proof of concept that both OX & CyC, if successfully potentiated, could be used against a wide range of ESKAPEE Gram-negative bacteria.
HostingRepository	PRIDE
AnnounceDate	2025-02-27
AnnouncementXML	Submission_2025-02-27_09:44:12.545.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AUDEBERT Stephane
SpeciesList	scientific name: Enterobacter cloacae; NCBI TaxID: 550;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-15 10:05:53	ID requested
⏵ 1	2025-02-27 09:44:12	announced

Dataset with its publication pending

submitter keyword: Gram-negative bacteria

Antibiotic resistance

drug enhancers

Oxadiazolone derivatives

Cyclipostins & Cyclophostin analogs

Activity based-protein profiling

Dr Jean-François CAVALIER,
contact affiliation	Lipolysis and Bacterial Pathogenicity Team, LISM UMR7255 CNRS, 32 chemin Joseph Aiguier - CS 70071, F-13402 Marseille cedex 09 (lab head)
contact email	jfcavalier@imm.cnrs.fr
lab head
AUDEBERT Stephane
contact affiliation	Marseille Proteomic, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact email	stephane.audebert@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053955
     1. Label: PRIDE project
     2. Name: The polyamino-isoprenyl enhancer NV716 potentializes the antibacterial activity of two families of multitarget inhibitors against the ESKAPEE bacterium Enterobacter cloacae, Part1bis (Enterobacter cloacae)