Data · study · 2026
Expression data from mice kidneys with urinary tract infection treated with NlpD or LytM
Listed in NCBI GEO
Finding new ways of treating bacterial infections is essential.
Description
The NlpD protein, which inhibits RNA Polymerase II (Pol II), has shown therapeutic efficacy against urinary tract infection. This study investigated the mechanism of Pol II inhibition and protection by NlpD and its LytM peptide.
Recombinant NlpD and LytM were screened for interactions with constituents of the RNA Polymerase II complex, using AlphaFold predictions and protein interaction technology. Treatment effects were quantified in infected tissues and regulated host response pathways identified by genome-wide transcriptomics analysis in models of acute pyelonephritis and acute cystitis in Irf3-/- and Asc-/- mice, respectively. LytM was shown to interact with constituents of the Pol II multiprotein complex, inhibiting the CDK12 kinase from phosphorylating the Pol II subunit RPB1 and disrupting Pol II complex formation by interfering with the interaction between PAF1C and RPB1.
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The protection by LytM against acute pyelonephritis was accompanied by a reduction in gene expression in infected kidneys from >1,900 significantly regulated genes (FC>6) in the placebo group to about 150 in LytM treated mice. The inhibition of gene expression in infected kidneys particularly targeted the excessive innate immune response. A similar effect was observed in acute cystitis.
Bacterial clearance was accelerated in both model by LytM treatment, with effects against antibiotic sensitive and resistant Escherichia coli strains. The results suggest that inhibiting the disease response of the host, using NlpD or LytM, may offer an efficient alternative to antibiotics in these models.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330388 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330388 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1463761 ncbi.nlm.nih.gov/bioproject/PRJNA1463761 ↗
project · from NCBI GEO
- PubMed 42090567 pubmed.ncbi.nlm.nih.gov/42090567 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by array · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE330388 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-array | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |