PXD033116

PXD033116 is an original dataset announced via ProteomeXchange.

Title	Chemoproteomics with a Diaryliodonium Probe in Bacteria
Description	The alarming increase in antimicrobial resistance (AMR) will soon limit treatment options for even routine infections, especially those caused by Gram-negative bacteria such as Acinetobacter baumannii. Here, we report a two-pronged approach to identify new vulnerabilities in such pathogens. Staring from diphenyleneiodonium (dPI) salts, which are compounds that have moderate antimicrobial activity against Gram-positive pathogens, we synthesized a focused heterocyclic library and report a new analogue that has much higher inhibitory potency against multidrug-resistant Acinetobacter baumannii and excellent efficacy in reduction of bacterial burden in a mouse neutropenic thigh infection model. The lead compound was also found to synergize with aminoglycosides, which are routinely used in the treatment of such infections in humans. Further, we synthesized an alkyne containing probe and using gel and mass spectrometry base chemoproteomics platforms, we identified proteins that have redox cofactors as putative targets for this class of compounds. Additionally, we also demonstrate that the modification of proteins is covalent and through a cysteine residue. Together, using complementary chemical biology approaches, new vulnerabilities in Gram-negative pathogens were identified that would help address a burgeoning global problem of AMR.
HostingRepository	PRIDE
AnnounceDate	2023-03-29
AnnouncementXML	Submission_2023-03-28_22:42:51.933.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SiddheshKamat
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Acinetobacter baumannii (strain ATCC 17978 / CIP 53.77 / LMG 1025 / NCDC KC755 / 5377); NCBI TaxID: 400667;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-08 10:32:17	ID requested
⏵ 1	2023-03-28 22:42:52	announced

submitter keyword: LC-MS/MS, Chemoproteomics

Siddhesh S.Kamat
contact affiliation	Associate Professor, Department of Biology, IISER Pune
contact email	siddhesh@iiserpune.ac.in
lab head
SiddheshKamat
contact affiliation	Indian Institute of Science Education and Research Pune
contact email	siddhesh@iiserpune.ac.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033116
     1. Label: PRIDE project
     2. Name: Chemoproteomics with a Diaryliodonium Probe in Bacteria