PXD059583-1

PXD059583 is an original dataset announced via ProteomeXchange.

Title	Francisella tularensis virulence is dependent on a conserved putative catalytic triad within the Type VI secretion system component PdpC
Description	Many Gram-negative bacteria utilize the ubiquitous and versatile type VI secretion systems (T6SS) for diverse purposes, such as outcompeting other microbes or to successfully colonize hosts. T6SS of common pathogens are classified as T6SSi, but an outlier is the T6SSii and it is present only in the genus Francisella. The highly virulent human pathogen Francisella tularensis harbors a variant of the T6SSii distinct from that of many other species of the genus, e.g., aquatic pathogens and tick endosymbionts. At the gene level, the most distinctive difference between the two variants is the presence in F. tularensis of a putative T6SS effector denoted PdpC. We here provide bioinformatic evidence that PdpC contains a conserved amino acid triad homologous to motifs present in toxins of the family Make Caterpillars Floppy. By site-directed mutagenesis, each of the three amino acids was substituted in cis in the live vaccine strain, LVS, of F. tularensis. Since the T6SS of F. tularensis is essential for the intracellular life cycle and virulence of the pathogen, the effects of the mutations were tested in mammalian cells and in a mouse model. It was observed that the resulting mutants demonstrated distinct phenotypes, evidenced as delayed, or no intramacrophage phagosomal escape, variable degrees of intramacrophage replication, and marked attenuation in mice. The corresponding mutants were also generated in the related species F. novicida, a commonly used model for F. tularensis, which conveniently allows studies of T6SS-mediated secretion. A mass spectrometry analysis of secreted proteins demonstrated that PdpC is one of several T6SS-dependent substrates, and that the lack of PdpC, or the presence of each of the amino acid-substituted mutant PdpC proteins, did not affect the secretion pattern of F. novicida. Collectively, the data demonstrate that the markedly attenuated phenotypes of the mutants were due to essential roles of the amino acid triad of PdpC.
HostingRepository	PRIDE
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-08_18:00:19.655.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shaochun Zhu
SpeciesList	scientific name: Francisella tularensis subsp. novicida (strain U112); NCBI TaxID: NEWT:401614;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-09 05:11:17	ID requested
⏵ 1	2026-03-08 18:00:21	announced

10.1093/femsmc/xtag009;

Br, ö, ms JE, Golovliov I, Alam A, Zhu S, Mateus A, Henry T, Sj, ö, stedt A, virulence relies on a conserved putative catalytic triad within the Type VI secretion system component PdpC. FEMS Microbes, 7():xtag009(2026) [pubmed]

submitter keyword: Virulence, Type VI Secretion System, Amino acid triad,Francisella tularensis, PdpC

Anders Sjöstedt
contact affiliation	Department of Clinical Microbiology,Umeå University, Umeå, Sweden
contact email	anders.sjostedt@umu.se
lab head
Shaochun Zhu
contact affiliation	Umea University
contact email	shaochunzhu@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059583
     1. Label: PRIDE project
     2. Name: Francisella tularensis virulence is dependent on a conserved putative catalytic triad within the Type VI secretion system component PdpC