PXD066928

PXD066928 is an original dataset announced via ProteomeXchange.

Title	p1/s1, a 3’-nucleotidase/nuclease, allows Leishmania to circumvent innate immune response mechanisms
Description	3’-nucleotidases/nucleases, distinct class I nucleases of protozoan parasites, play a pivotal role in extracellular purine salvage. As Leishmania are purine auxotroph and lack de novo synthesis, ectoenzymes facilitating nucleotide and nucleic acid cleavage are indispensable for subsequent uptake. Employing quantitative proteomics, we identified a class I nuclease p1/s1 cluster in L. major that comprises enzymes exhibiting dual 3’-nucleotidase and endonuclease activity. Expression of these enzymes is induced upon miltefosine or staurosporine treatment and was specifically detected in stationary phase, but not in logarithmic phase promastigotes. After confirming secretion of p1/s1, ecto-enzymatic activity was detected on parasites and in the culture supernatant. Viable null mutants deficient for the p1/s1 cluster were only obtained when a diCre-based inducible knockout system was applied, whereas direct deletion approaches were lethal. The viable knockout strains exhibited significantly reduced 3’-nucleotidase/nuclease activity. Notably, these parasites adapted by compensatory enrichment of various alternative purine salvage proteins on the proteomic level. Furthermore, both enzymatic functions implied mechanisms of host-pathogen interactions to facilitate infection establishment: Utilizing 3’-nucleotidase activity, Leishmania generate extracellular adenosine to suppress inflammatory cytokine secretion from macrophages and reduce lymphocyte proliferation in a human primary cell model. The presence of ecto-nucleases also allowed these parasites to degrade and survive neutrophil extracellular traps, a potent first-line innate immune mechanism in pathogen defense. In summary, our integrative approach combining proteomics, immunological and genome editing methods expands current knowledge about Leishmania major 3’-nucleotidases/nucleases. By offering new insights into the diverse involvements in host-pathogen interactions, we highlight p1/s1 as pivotal infection factor and potential drug target.
HostingRepository	jPOST
AnnounceDate	2026-05-05
AnnouncementXML	Submission_2026-05-05_01:13:57.678.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tanja Ziesmann
SpeciesList	scientific name: Leishmania major; NCBI TaxID: 5664;
ModificationList	S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide
Instrument	timsTOF SCP; Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-04 07:40:16	ID requested
⏵ 1	2026-05-05 01:13:58	announced

Dataset with its publication pending

submitter keyword: Leishmania major, 3‘-nucleotidase/nuclease, host-pathogen-interactions, purine metabolism, stress-related proteins

Ger van Zandbergen
lab head
Tanja Ziesmann
contact affiliation	Insitute of Immunology, University Medical Center Mainz
dataset submitter

jPOST dataset URI

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