PXD033396-1

PXD033396 is an original dataset announced via ProteomeXchange.

Title	Mechanisms of chlorate toxicity and resistance in Pseudomonas aeruginosa
Description	Pseudomonas aeruginosa is an opportunistic pathogen known to cause both acute and chronic infections. P. aeruginosa often encounters hypoxic/anoxic environments within the host, which increases its tolerance to many conventional antibiotics. Towards identifying novel therapeutic treatments, we have been exploring the potential of chlorate, a pro-drug that kills hypoxic/anoxic, antibiotic-tolerant P. aeruginosa populations. Chlorate kills P. aeruginosa when it is enzymatically reduced by hypoxically-induced nitrate reductase, thereby generating the toxic oxidizing agent, chlorite. To better assess its therapeutic potential, we investigated mechanisms of chlorate toxicity and resistance in P. aeruginosa. We combined transposon mutagenesis and high-throughput sequencing to identify genes that alter P. aeruginosa fitness during chlorate treatment. We found that methionine sulfoxide reductase (msr) genes, whose products repair oxidized methionine residues, support survival during chlorate stress. We showed that chlorate treatment leads to proteome-wide methionine oxidation, which is exacerbated in a ∆msrA∆msrB strain. Highly abundant proteins were the likeliest targets of methionine oxidation, including proteins that are abundant under standard conditions (e.g. ribosomes) and proteins that increase in abundance in response to chlorate stress (e.g. protein chaperones). The addition of exogenous methionine partially rescued P. aeruginosa survival during chlorate treatment, suggesting that widespread methionine oxidation contributes to cell death. Finally, we found that decreased nitrate reductase activity is a common mechanism of chlorate resistance. Because nitrate respiration likely sustains P. aeruginosa anaerobic growth and survival within the host, developing chlorate resistance would be expected to hinder pathogen fitness in such environments.
HostingRepository	PRIDE
AnnounceDate	2023-10-24
AnnouncementXML	Submission_2023-10-24_11:17:12.057.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JeffJones
SpeciesList	scientific name: Pseudomonas aeruginosa (strain UCBPP-PA14); NCBI TaxID: 208963;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-23 15:33:58	ID requested
⏵ 1	2023-10-24 11:17:12	announced
2	2023-11-14 09:07:33	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:08:47	announced	2024-10-22: Updated project metadata.

Spero MA, Jones J, Lomenick B, Chou TF, Newman DK, Mechanisms of chlorate toxicity and resistance in Pseudomonas aeruginosa. Mol Microbiol, 118(4):321-335(2022) [pubmed]

submitter keyword: resistance,chlorate toxicity, Pseudomonas aeruginosa

Tsui-FenChou
contact affiliation	Faculity Director: Caltech, Beckman Institute, Proteome Exploration Laboratory
contact email	tfchou@caltech.edu
lab head
JeffJones
contact affiliation	California Institute of Technology
contact email	jeffj@caltech.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033396
     1. Label: PRIDE project
     2. Name: Mechanisms of chlorate toxicity and resistance in Pseudomonas aeruginosa