Evidence map›Paper›PMID 22753374›Full record

ArticleInfection and immunity2012

Phosphate groups of lipid A are essential for Salmonella enterica serovar Typhimurium virulence and affect innate and adaptive immunity.

Qingke Kong, David A Six, Qing Liu, Lillian Gu, Shifeng Wang, Praveen Alamuri, Christian R H Raetz, Roy Curtiss

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
8.1field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 84 citations in OpenAlex.

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  17. The Anti-Inflammatory Effects ofMolecules (Basel, Switzerland) · 2023
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  20. Review
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

8 authors at 3 institutions in 1 country.

Qingke KongCenter for Infectious Diseases and Vaccinology, Biodesign Institute, Arizona State University, Tempe, Arizona, USA. Qingke.kong@asu.edu
David A Six
Qing Liu
Lillian Gu
Shifeng Wang
Praveen Alamuri
Christian R H Raetz
Roy Curtiss
Arizona State University · USDuke University Hospital · USDuke Medical Center · US

Funding

STEROL LIPIDSU54GM069338 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 2003 to 2013
$72.2M
Recombinant Attenuated Salmonella Vaccines for HumansR01AI056289 · NIAID · WASHINGTON UNIVERSITY · PI CLARK-CURTISS, JOSEPHINE E, CURTISS III, ROY · 2003 to 2018
$5.8M
LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIAR37GM051796 · NIGMS · DUKE UNIVERSITY · PI RAETZ, CHRISTIAN R · 1999 to 2008
$3.0M
Salmonella Vaccines Against Bacterial EnteropathogensR01AI060557 · NIAID · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI CURTISS III, ROY · 2010 to 2014
$2.2M
Lipid A Modification Systems in Gram-Negative BacteriaR01GM051796 · NIGMS · DUKE UNIVERSITY · PI ZHOU, PEI · 1995 to 2012
$1.5M
S. typhimiurium Vaccine Against Bacterial EnteropathogensU01AI060557 · NIAID · WASHINGTON UNIVERSITY · PI CURTISS, ROY · 2003 to 2007
$1.4M
NIAID NIH HHS AI056289NIAID NIH HHS AI060557NIAID NIH HHS R01 AI056289NIAID NIH HHS R01 AI060557NIAID NIH HHS U01 AI060557NIGMS NIH HHS GM-069338NIGMS NIH HHS GM-51796NIGMS NIH HHS R01 GM051796NIGMS NIH HHS R37 GM051796NIGMS NIH HHS U54 GM069338
6 · The paper itself

Abstract

Lipid A is a key component of the outer membrane of Gram-negative bacteria and stimulates proinflammatory responses via the Toll-like receptor 4 (TLR4)-MD2-CD14 pathway. Its endotoxic activity depends on the number and length of acyl chains and its phosphorylation state. In Salmonella enterica serovar Typhimurium, removal of the secondary laurate or myristate chain in lipid A results in bacterial attenuation and growth defects in vitro. However, the roles of the two lipid A phosphate groups in bacterial virulence and immunogenicity remain unknown. Here, we used an S. Typhimurium msbB pagL pagP lpxR mutant, carrying penta-acylated lipid A, as the parent strain to construct a series of mutants synthesizing 1-dephosphorylated, 4'-dephosphorylated, or nonphosphorylated penta-acylated lipid A. Dephosphorylated mutants exhibited increased sensitivity to deoxycholate and showed increased resistance to polymyxin B. Removal of both phosphate groups severely attenuated the mutants when administered orally to BALB/c mice, but the mutants colonized the lymphatic tissues and were sufficiently immunogenic to protect the host from challenge with wild-type S. Typhimurium. Mice receiving S. Typhimurium with 1-dephosphorylated or nonphosphorylated penta-acylated lipid A exhibited reduced levels of cytokines. Attenuated and dephosphorylated Salmonella vaccines were able to induce adaptive immunity against heterologous (PspA of Streptococcus pneumoniae) and homologous antigens (lipopolysaccharide [LPS] and outer membrane proteins [OMPs]).

Indexed as

Adaptive ImmunityAnimalsDisease Models, AnimalFemaleHumansImmunity, InnateLipid AMiceMice, Inbred BALB CPhosphatesSalmonella InfectionsSalmonella typhimuriumSalmonella VaccinesStreptococcus pneumoniaeVaccines, AttenuatedVirulenceLipid APhosphatesSalmonella VaccinesVaccines, AttenuatedVirulence Factors

Identifiers

PMID22753374
PMCPMC3418755
OpenAlexW2150292428

What OpenQuestion holds

Textmetadata
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.