PXD017318

PXD017318 is an original dataset announced via ProteomeXchange.

Title	Mechanism of BceAB-type transporter: Resistance by lipid II flipping
Description	Treatment of bacterial infections are the great challenge of our era due to the evolved resistance mechanisms against antibiotics. The Achilles heel of bacteria is the cell wall especially during the needs of its synthesis and cell division. Here lipid II is an essential precursor component synthesized in the cytosol and flipped into the outer leaflet of the membrane prior to application into the cell wall. Compounds targeting the cell wall or its biosynthesis precursors have been around for decades and have been used as antibiotics against bacterial infections like meningitis, pneumonia and endocarditis. In the last decades however resistance against those antibiotics evolved and antimicrobial peptides (AMPs) have been found to be promising alternative antibiotics. The Bacitracin efflux (BceAB)-type ATP binding cassette transporters expressed in the membrane of human pathogenic bacteria confer resistance against these alternative antibiotics and thereby their medical development is hampered. Here we elucidated the mechanism of the BceAB-type transporter NsrFP from Streptococcus agalactiae COH1 (SaNsrFP), described to confer high resistance against the antimicrobial peptide nisin, a member of the lantibiotic subfamily. We showed that SaNsrFP is using a novel mechanism of resistance by flipping lipid II back into the cytosol thereby preventing the binding of nisin as well as other lipid II targeting compounds. This trick is intriguing since it uses a relative simple mechanism resulting in the resistance of the human pathogenic bacteria against a structurally divers group of potent antibiotics.
HostingRepository	PRIDE
AnnounceDate	2022-05-25
AnnouncementXML	Submission_2022-05-25_04:28:48.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nina Overbeck
SpeciesList	scientific name: Lactococcus lactis subsp. cremoris NZ9000; NCBI TaxID: 746361;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-29 05:27:07	ID requested
⏵ 1	2022-05-25 04:28:50	announced

Gottstein J, Zaschke-Kriesche J, Unsleber S, Voitsekhovskaia I, Kulik A, Behrmann LV, Overbeck N, St, ü, hler K, Stegmann E, Smits SHJ, New insights into the resistance mechanism for the BceAB-type transporter SaNsrFP. Sci Rep, 12(1):4232(2022) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: BceAB-type, antibiotic resistance, nisin, bacitracin, lipid II

Kai Stühler
contact affiliation	Institute for Molecular Medicine I Medical Faculty Heinrich-Heine-University Duesseldorf Universitaetsstrasse 1 40225 Duesseldorf Germany
contact email	kai.stuehler@hhu.de
lab head
Nina Overbeck
contact affiliation	BMFZ/MPL
contact email	nina.overbeck@hhu.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017318
     1. Label: PRIDE project
     2. Name: Mechanism of BceAB-type transporter: Resistance by lipid II flipping