PXD056440-1

PXD056440 is an original dataset announced via ProteomeXchange.

Title	Blockage of O-linked glycan biosynthesis in Burkholderia is toxic: OgcX complementation
Description	Burkholderia species are associated with several life-threatening human infections, often resulting in high morbidity and mortality rates due to their innate resistance to antibiotics. To improve clinical outcomes, new therapies targeting conserved, yet unique, Burkholderia pathways are needed. One such pathway is the Burkholderia O-linked protein glycosylation system, essential for virulence in Burkholderia cenocepacia and Burkholderia pseudomallei. This system relies on the O-Glycosylation gene Cluster (OGC), a five-gene cluster sufficient and required for the generation of a trisaccharide β-Gal-(1,3)–α-GalNAc-(1,3)–β-GalNAc used for protein glycosylation, and the distally encoded oligosaccharyltransferase, pglL, responsible for ligating glycans to glycoproteins. Previous work has shown that the OGC cluster can be removed, but individual mutations associated with late-stage glycan biosynthesis are essential. Here, we explore the essentiality of late-stage O-linked glycan biosynthesis in B. cenocepacia, revealing that the completion and translocation of the O-linked trisaccharide is necessary for viability and bacterial fitness. Using inducible systems, we demonstrate toxicity dependent on multiple OGC genes and the initiation of O-linked glycan biosynthesis. Upon loss of late-stage biosynthesis, mutants exhibit notable growth defects and profound sensitivity to stresses. Proteomics and glycoproteomic analysis show that blocking late-stage glycan biosynthesis inhibits protein glycosylation and drives large membrane proteomic changes. Finally, we demonstrate that OGC mediated toxicity is not limited to blockages but can also occur via the overexpression of steps within O-linked glycan biosynthesis. Combined, these findings suggest that the O-linked glycan biosynthesis pathway of B. cenocepacia is extremely sensitive to dysregulation and may be an ideal target for the development of antimicrobial therapies.
HostingRepository	PRIDE
AnnounceDate	2025-10-22
AnnouncementXML	Submission_2025-10-22_01:28:02.444.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nichollas Scott
SpeciesList	scientific name: Burkholderia cenocepacia K56-2Valvano; NCBI TaxID: NEWT:985076;
ModificationList	complex glycosylation
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-02 01:47:45	ID requested
⏵ 1	2025-10-22 01:28:03	announced

10.1016/j.jbc.2025.108515;

Jebeli L, McDaniels TA, Ho DTT, Tahir H, Kai-Ming NL, Mcgaw M, Karlic KI, Lewis JM, Scott NE, The late-stage steps of Burkholderia cenocepacia protein O-linked glycan biosynthesis are conditionally essential. J Biol Chem, 301(6):108515(2025) [pubmed]

submitter keyword: glycosylation,Burkholderia

Nichollas E. Scott
contact affiliation	Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for infection and immunity, Melbourne, 3000, Australia
contact email	nichollas.scott@unimelb.edu.au
lab head
Nichollas Scott
contact affiliation	University of Melbourne
contact email	nichollas.scott@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056440
     1. Label: PRIDE project
     2. Name: Blockage of O-linked glycan biosynthesis in Burkholderia is toxic: OgcX complementation