PXD025370

PXD025370 is an original dataset announced via ProteomeXchange.

Title	Nucleoside Analogues are Potent Inducers of Bacterial Mutagenesis
Description	Drugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the potential to increase mutagenesis and the development of antimicrobial resistance (AMR). Here we have examined nucleoside analogues (NAs) commonly used in anti-viral and anti-cancer therapies for potential effects on mutagenesis in Escherichia coli using the Rifampicin mutagenicity assay. To further explore the mode of action of the NAs, we appliedanalyzed metabolome and proteome of E.coli deletion mutants., and metabolome and proteome analyses. Five out of the thirteen NAs examined, including three nucleoside reverse transcriptase inhibitors (NRTIs) and two anti-cancer drugs, increased the mutation frequency in E. coli more than 25-fold at doses that were within reported plasma concentration range (Pl.CR), but that did not affect bacterial growth. We show that the SOS response is induced and that the increase in mutation frequency is mediated by the TLS polymerase Pol V. Quantitative mass spectrometry based metabolite profiling did not reveal large changes in nucleoside phosphate or other central carbon metabolite pools, which suggests that the SOS induction is an effect of increased replicative stress. Our results suggest that NAs/NRTIs can contribute to the development of AMR.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:41.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Animesh Sharma
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-13 04:39:44	ID requested
1	2021-07-15 03:04:01	announced
⏵ 2	2023-11-14 08:52:41	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: NA, -clamp, TLS, MDR, Pol V, NRTIs, SOS, AMR

Marit Otterlei
contact affiliation	Professor, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), PO Box 8905, N-7491, Trondheim, Norway Phone: +47 72573075, Fax: +47 72576400
contact email	marit.otterlei@ntnu.no
lab head
Animesh Sharma
contact affiliation	Engineer at NTNU, Norway
contact email	sharma.animesh@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/07/PXD025370

PRIDE project URI

• PRIDE
  1. PXD025370
     1. Label: PRIDE project
     2. Name: Nucleoside Analogues are Potent Inducers of Bacterial Mutagenesis