Evidence map›Paper›PMID 31740807›Full record

ArticleNature chemical biology2020

Site-specific acylation of a bacterial virulence regulator attenuates infection.

Zhenrun J Zhang, Virginia A Pedicord, Tao Peng, Howard C Hang

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 84 citations in OpenAlex.

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  14. Propionylation of Fis K32 inFuture microbiology · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 3 countries.

Zhenrun J ZhangLaboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY, USA.
Virginia A PedicordLaboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY, USA.
Tao PengLaboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY, USA.
Howard C HangLaboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY, USA. hhang@rockefeller.edu.ORCID http://orcid.org/0000-0003-4053-5547
Rockefeller University · USPeking University · CNUniversity of Cambridge · GB

Funding

Studies on Protein LipidationR01GM087544 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI HANG, HOWARD C · 2010 to 2023
$4.4M
Mechanistic analysis of flavonoids on bacterial virulenceR01AT007671 · NCCIH · ROCKEFELLER UNIVERSITY · PI GALAN, JORGE E, HANG, HOWARD C · 2012 to 2016
$2.4M
Distal gut microbiome targets of host anti-proteolytic proteins during colitisR21AI156674 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI HANG, HOWARD C · 2021 to 2022
$488k
NCCIH NIH HHS R01 AT007671NIAID NIH HHS R21 AI156674NIGMS NIH HHS R01 GM087544U.S. Department of Health & Human Services | NIH | National Center for Complementary and Integrative Health (NCCIH) R01AT007671U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM087544
6 · The paper itself

Abstract

Microbiota generates millimolar concentrations of short-chain fatty acids (SCFAs) that can modulate host metabolism, immunity and susceptibility to infection. Butyrate in particular can function as a carbon source and anti-inflammatory metabolite, but the mechanism by which it inhibits pathogen virulence has been elusive. Using chemical proteomics, we found that several virulence factors encoded by Salmonella pathogenicity island-1 (SPI-1) are acylated by SCFAs. Notably, a transcriptional regulator of SPI-1, HilA, was acylated on several key lysine residues. Subsequent incorporation of stable butyryl-lysine analogs using CRISPR-Cas9 gene editing and unnatural amino acid mutagenesis revealed that site-specific modification of HilA impacts its genomic occupancy, expression of SPI-1 genes and attenuates Salmonella enterica serovar Typhimurium invasion of epithelial cells, as well as dissemination in vivo. Moreover, a multiple-site HilA lysine acylation mutant strain of S. Typhimurium was resistant to butyrate inhibition ex vivo and microbiota attenuation in vivo. Our results suggest that prominent microbiota-derived metabolites may directly acylate virulence factors to inhibit microbial pathogenesis in vivo.

Indexed as

Gene Expression Regulation, BacterialGenomic IslandsVirulenceAnimalsArginineBacterial ProteinsBinding SitesButyratesCRISPR-Cas SystemsFatty AcidsGenome, BacterialGenomicsLysineMiceMice, Inbred C57BLMutagenesisArginineBacterial ProteinsButyratesFatty AcidsLysineTrans-ActivatorsVirulence Factors

Identifiers

PMID31740807
PMCPMC8439376
OpenAlexW2986694036

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.