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PXD017318

PXD017318 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMechanism of BceAB-type transporter: Resistance by lipid II flipping
DescriptionTreatment 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.
HostingRepositoryPRIDE
AnnounceDate2022-05-25
AnnouncementXMLSubmission_2022-05-25_04:28:48.989.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNina Overbeck
SpeciesList scientific name: Lactococcus lactis subsp. cremoris NZ9000; NCBI TaxID: 746361;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-01-29 05:27:07ID requested
12022-05-25 04:28:50announced
Publication List
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]
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: BceAB-type, antibiotic resistance, nisin, bacitracin, lipid II
Contact List
Kai Stühler
contact affiliationInstitute for Molecular Medicine I Medical Faculty Heinrich-Heine-University Duesseldorf Universitaetsstrasse 1 40225 Duesseldorf Germany
contact emailkai.stuehler@hhu.de
lab head
Nina Overbeck
contact affiliationBMFZ/MPL
contact emailnina.overbeck@hhu.de
dataset submitter
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