ArticleThe Journal of clinical investigation2021
Active bacterial modification of the host environment through RNA polymerase II inhibition.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Targeting the Disease Response With NlpD and LytM for Effective Nonantibiotic Treatment of Urinary Tract Infections.The Journal of infectious diseases · 2026Article
- Transposon-insertion sequencing reveals NlpD as a vulnerability in intracellular survival and pathogenesis of Salmonella 4,[5],12:i:.PLoS pathogens · 2026Article
- Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.International journal of molecular sciences · 2024Article
- Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains.Pathogens (Basel, Switzerland) · 2023Article
- Immunomodulation therapy offers new molecular strategies to treat UTI.Nature reviews. Urology · 2022Review
- Collateral effects of deletion of nlpD on rpoS and rpoS-dependent genes. Reply.The Journal of clinical investigation · 2021Article
- Collateral effects of deletion of nlpD on rpoS and rpoS-dependent genes.The Journal of clinical investigation · 2021Article
- Molecular determinants of disease severity in urinary tract infection.Nature reviews. Urology · 2021Review
- A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer.Nature biotechnology · 2021Article
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unlike pathogens, which attack the host, commensal bacteria create a state of friendly coexistence. Here, we identified a mechanism of bacterial adaptation to the host niche, where they reside. Asymptomatic carrier strains were 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 was identified as a Pol II inhibitor. After internalization by host cells, NlpD was shown to target constituents of the Pol II phosphorylation complex (RPB1 and PAF1C), attenuating host gene expression. Therapeutic efficacy of a recombinant NlpD protein was 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 remarkable therapeutic potential.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.