PXD043195

PXD043195 is an original dataset announced via ProteomeXchange.

Title	Same same but different – The global response of Escherichia coli to five different LpxC inhibitors
Description	A promising but yet clinically unexploited antibiotic target in difficult-to-treat Gram-negative bacteria is LpxC, the key enzyme in the biosynthesis of lipopolysaccharides (LPS), which are the major constituents of the outer membrane. To gain insights into the mode of action of five different LpxC inhibitors, we conducted a comparative phenotypic and proteomic analysis. All five compounds bound to purified LpxC from Escherichia coli. Treatment of E. coli with these compounds changed the cell shape and stabilized LpxC indicating that the inhibitor-bound enzyme is not degraded by the FtsH protease. LpxC inhibition sensitized E. coli to the cell wall antibiotic vancomycin, which typically does not cross the outer membrane. Four of the five compounds led to an accumulation of lyso-PE, a cleavage product of phosphatidylethanolamine (PE), generated by the phospholipase PldA. The combined results suggested an imbalance in phospholipid (PL) and LPS biosynthesis, which was corroborated by the global proteome response to treatment with the LpxC inhibitors. Apart from LpxC itself, FabA and FabB responsible for the biosynthesis of unsaturated fatty acids were consistently upregulated. Our work also shows that antibiotics targeting the same enzyme do not necessarily elicit identical cellular responses. Compound-specific marker proteins belonged to different functional categories, like stress responses, nucleotide or amino acid metabolism and quorum sensing. These findings provide new insights into common and distinct cellular defense mechanisms against LpxC inhibition. Moreover, they support a delicate balance between LPS and PL biosynthesis with great potential as point of attack for antimicrobial intervention.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:48.204.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sina Schäkermann
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Waters raw format

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-21 22:24:14	ID requested
1	2024-10-08 11:14:46	announced
⏵ 2	2024-10-22 06:45:51	announced	2024-10-22: Updated project metadata.

10.1016/j.jbc.2024.107143;

M, ö, ller AM, V, á, zquez-Hern, á, ndez M, Kutscher B, Brysch R, Br, ü, ckner S, Marino EC, Kleetz J, Senges CHR, Sch, ä, kermann S, Bandow JE, Narberhaus F, Common and varied molecular responses of Escherichia coli to five different inhibitors of the lipopolysaccharide biosynthetic enzyme LpxC. J Biol Chem, 300(4):107143(2024) [pubmed]

submitter keyword: lipopolysaccharide, LPS, antibiotics, phospholipid,Outer membrane, FtsH

Prof. Dr. Julia E. Bandow
contact affiliation	Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany
contact email	julia.bandow@rub.de
lab head
Sina Schäkermann
contact affiliation	Ruhr-Universität Bochum
contact email	Sina.Langklotz@rub.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043195
     1. Label: PRIDE project
     2. Name: Same same but different – The global response of Escherichia coli to five different LpxC inhibitors