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PXD031065

PXD031065 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUptake mechanisms and regulatory responses to MECAM- and DOTAM-based artificial siderophores and their antibiotic conjugates in Pseudomonas aeruginosa
DescriptionThe development of new antibiotics against Gram-negative bacteria has to deal with the low permeability of the outer membrane. This obstacle can be overcome by utilizing siderophore-dependent iron uptake pathways as gates for antibiotic uptake. Iron-chelating siderophores are actively imported by bacteria, and their conjugation to antibiotics allows smuggling the latter into bacterial cells. Synthetic siderophore mimetics based on MECAM and DOTAM cores, both chelating iron via catechol groups, have been recently applied as versatile carriers of functional cargo. In the present study, we show that MECAM and the MECAM-ampicillin conjugate 3 transport iron into Pseudomonas aeruginosa cells via the catechol-type outer membrane transporters PfeA and PirA, and DOTAM solely via PirA. Differential proteomics and RTqPCR showed that MECAM import induced the expression of pfeA, whereas 3 led to an increase in the expression of pfeA and ampc, a gene conferring ampicillin resistance. The presence of DOTAM did not induce the expression of pirA, but upregulated the expression two zinc transporters (cntO and PA0781), pointing out that bacteria become zinc starved in the presence of this compound. Kinetic experiments with radioactive 55Fe demonstrated that iron uptake was as efficient as with the natural prototype siderophore enterobactin. The study provides a mechanistic and functional validation for DOTAM- and MECAM-based artificial siderophore mimetics as vehicles for the delivery of cargo into Gram-negative bacteria.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:25:13.344.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD031065
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterLauriane Kuhn
SpeciesList scientific name: Pseudomonas aeruginosa PAO1; NCBI TaxID: 208964;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-19 02:39:10ID requested
12022-10-28 06:46:44announced
22023-11-14 08:25:15announced2023-11-14: Updated project metadata.
Publication List
10.6019/PXD031065;
Fritsch S, Gasser V, Peukert C, Pinkert L, Kuhn L, Perraud Q, Normant V, Br, ö, nstrup M, Schalk IJ, . ACS Infect Dis, 8(6):1134-1146(2022) [pubmed]
Keyword List
submitter keyword: antibiotic conjugate, Pseudomnas, DOTAM,siderophore, MECAM
Contact List
Isabelle Schalk
contact affiliationCNRS, University of Strasbourg, UMR7242, UMR7242, ESBS, Bld Sébastien Brant, F-67412 Illkirch, Strasbourg, France. University of Strasbourg, UMR7242, ESBS, Bld Sébastien Brant, F-67412 Illkirch, Strasbourg, France.
contact emailisabelle.schalk@unistra.fr
lab head
Lauriane Kuhn
contact affiliationCNRS, IBMC, FRC1589
contact emaill.kuhn@ibmc-cnrs.unistra.fr
dataset submitter
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Dataset FTP location
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