PXD030906

PXD030906 is an original dataset announced via ProteomeXchange.

Title	Evolutionary collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium
Description	The rise of antibiotic resistance and decline of antibiotic discovery urgently calls for novel mechanistic understanding of pharmacological and evolutionary interactions between antibiotics and multidrug resistant bacteria to revitalize existing antibiotics. The evolutionary cross-resistance to antibiotics has received intensive attention previously. Nevertheless, whether and how bacteria develop negative responses, under the selective pressure of antibiotics by inverting the evolutionary trajectory remains unclear. Here we found an instance of collateral sensitivity, in which clinical vancomycin-resistant Enterococcus faecium (VREfm) pathogens exhibit dramatic and specific susceptibility to pleuromutilin antibiotics, decreased minimal inhibitory concentrations (MICs) from 128 µg/mL to 0.03 µg/mL. The unique trade-off between vancomycin and pleuromutilins is mediated by the epistasis between the van gene cluster and msrC encoding an ABC-F protein protecting bacterial ribosomes. We validated the efficacy of pleuromutilins in vivo through reducing colonization and promoting microbiota restoration. Our findings provide an alternative approach to inverting the selective advantage and reversing the route of vancomycin resistance evolution, and to treat VREfm associated infections.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_05:17:46.105.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	hanzhong feng
SpeciesList	scientific name: Enterococcus faecalis (Streptococcus faecalis); NCBI TaxID: 1351;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-12 00:29:51	ID requested
⏵ 1	2022-05-20 05:17:46	announced

Li Q, Chen S, Zhu K, Huang X, Huang Y, Shen Z, Ding S, Gu D, Yang Q, Sun H, Hu F, Wang H, Cai J, Ma B, Zhang R, Shen J, Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium. Nat Commun, 13(1):1888(2022) [pubmed]

submitter keyword: collateral sensitivity，vancomycin-resistant Enterococcus faecium，pleuromutilin

Kui Zhu
contact affiliation	College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
contact email	zhukcau@163.com
lab head
hanzhong feng
contact affiliation	Lanzhou University
contact email	fenghzh19@lzu.edu.cn
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/2022/05/PXD030906

PRIDE project URI

• PRIDE
  1. PXD030906
     1. Label: PRIDE project
     2. Name: Evolutionary collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium