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| Status |
Public on Dec 11, 2020 |
| Title |
Expression data profile of A498 cells infected with E. coli 83972, mutants or stimualted with rNlpD |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Unlike pathogens, which attack the host, commensal bacteria create a state of friendly coexistence. Here, we identify a new mechanism of bacterial adaptation to the host niche, where they reside. Asymptomatic carrier strains are shown to inhibit RNA Polymerase II (Pol II) in host cells by targeting Ser2 phosphorylation; a step required for productive mRNA elongation. Assisted by a rare, spontaneous loss-of-function mutant from a human carrier, the bacterial NlpD protein is identified as a Pol II inhibitor. After internalization by host cells, NlpD is shown to target constituents of the Pol II phosphorylation complex (RPB1 and PAF1C), attenuating host gene expression. Therapeutic efficacy of the rNlpD protein is demonstrated in a urinary tract infection model, by reduced tissue pathology, accelerated bacterial clearance and attenuated Pol II-dependent gene expression. The findings suggest an intriguing, evolutionarily conserved mechanism for bacterial modulation of host gene expression, with a significant therapeutic potential.
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| Overall design |
A498 kidney epithelial cells were infected with 10^5 CFU/ml of E. coli 83972, SN25 or SN25-pRH320 or treated with bacterial supernatants or recombinant NlpD protein for 4 hours. Cells with culture medium with PBS were used as a control. Isolated RNA was subjected to Affymetrix whole genome transcriptome analysis.
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| Contributor(s) |
Ambite I, Svanborg C |
| Citation(s) |
33320835 |
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| Submission date |
Nov 25, 2020 |
| Last update date |
Feb 16, 2021 |
| Contact name |
Ines Ambite |
| E-mail(s) |
[email protected]
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| Organization name |
Lund University
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| Department |
Laboratory Medicine
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| Lab |
MIG
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| Street address |
Klinikgatan 28
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| City |
Lund |
| ZIP/Postal code |
22184 |
| Country |
Sweden |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA680811 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE162190_RAW.tar |
33.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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