PXD018347

PXD018347 is an original dataset announced via ProteomeXchange.

Title	Triclocarban vs Triclosan: A look into the protein targets of chlorinated biphenyl antimicrobials
Description	Triclocarban (TCC), a formerly used disinfectant, kills bacteria via an unknown mechanism of action. A structural hallmark is its N,N'-diaryl urea motif which is also present in other antibiotics including the recently reported small molecule PK150. Like PK150, TCC exhibited a similar inhibitory effect on menaquinone metabolism via inhibition of the biosynthesis protein MenG, suggesting a contribution of this pathway to its mode of action. However, the activity spectrum (MIC90) of TCC across a broad range of resistant staphylococci and enterococci strains was much narrower compared to PK150. Accordingly, TCC did not cause an overactivation of signal peptidase SpsB, a hallmark of the PK150 scaffold. Furthermore, we were able to rule out inhibition of FabI, a confirmed target of the diaryl ether antibiotic triclosan (TCS). Differences in the target profile of TCC and TCS were further investigated by proteomic analysis, showing complex, but rather distinct changes in the protein expression profile of the bacteria. Additional evidence for an effect on bacterial energy metabolism was provided for TCC. Taken together, this study shows that N,N'-diaryl urea motifs exhibit shared and distinct molecular targets and for the first time highlights MenG as a target of TCC.
HostingRepository	PRIDE
AnnounceDate	2020-06-04
AnnouncementXML	Submission_2020-06-04_03:09:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robert Macsics
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-03 02:14:38	ID requested
⏵ 1	2020-06-04 03:21:04	announced

Dataset with its publication pending

submitter keyword: Triclocarban, triclosan, antibacterials, full proteome analysis, Q Exactive Plus, LFQ

Stephan Axel Sieber
contact affiliation	Department of Chemistry Chair of Organic Chemistry II Technical University of Munich Germany
contact email	stephan.sieber@tum.de
lab head
Robert Macsics
contact affiliation	Technical University of Munich
contact email	robert.macsics@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018347
     1. Label: PRIDE project
     2. Name: Triclocarban vs Triclosan: A look into the protein targets of chlorinated biphenyl antimicrobials