Evidence map›Paper›PMID 26902724›Full record

ArticleInfection and immunity2016

The Protease Locus of Francisella tularensis LVS Is Required for Stress Tolerance and Infection in the Mammalian Host.

Lihong He, Manoj Kumar Mohan Nair, Yuling Chen, Xue Liu, Mengyun Zhang, Karsten R O Hazlett, Haiteng Deng, Jing-Ren Zhang

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Lihong HeCenter for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
Manoj Kumar Mohan NairCenter for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Yuling ChenMOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Xue LiuCenter for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
Mengyun ZhangCenter for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
Karsten R O HazlettCenter for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Haiteng DengMOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China dengh@biomed.tsinghua.edu.cn zhanglab@tsinghua.edu.cn.
Jing-Ren ZhangCenter for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China dengh@biomed.tsinghua.edu.cn zhanglab@tsinghua.edu.cn.
Tsinghua University · CNAlbany Medical Center Hospital · USSichuan University · CN

Funding

TLR2/NLR Signal Regulation of Protective Immunity to F. TularensisP01AI056320 · NIAID · ALBANY MEDICAL COLLEGE · PI METZGER, DENNIS W · 2003 to 2016
$22.9M
Criteria-Directed Vaccine Generation Via Ag Mimicry, Adjuvancy, And APC-TargetingR01AI100138 · NIAID · ALBANY MEDICAL COLLEGE · PI GOSSELIN, EDMUND J, HAZLETT, KARSTEN R.O. · 2013 to 2017
$2.9M
Functional analysis of the Francisella capBCA gene locusR21AI083963 · NIAID · ALBANY MEDICAL COLLEGE · PI ZHANG, JING-REN · 2009 to 2010
$430k
NIAID NIH HHS P01 AI056320NIAID NIH HHS R01 AI100138NIAID NIH HHS R21 AI083963
6 · The paper itself

Abstract

Francisella tularensis is the causative agent of tularemia and a category A potential agent of bioterrorism, but the pathogenic mechanisms of F. tularensis are largely unknown. Our previous transposon mutagenesis screen identified 95 lung infectivity-associated F. tularensis genes, including those encoding the Lon and ClpP proteases. The present study validates the importance of Lon and ClpP in intramacrophage growth and infection of the mammalian host by using unmarked deletion mutants of the F. tularensis live vaccine strain (LVS). Further experiments revealed that lon and clpP are also required for F. tularensis tolerance to stressful conditions. A quantitative proteomic comparison between heat-stressed LVS and the isogenic Lon-deficient mutant identified 29 putative Lon substrate proteins. The follow-up protein degradation experiments identified five substrates of the F. tularensis Lon protease (FTL578, FTL663, FTL1217, FTL1228, and FTL1957). FTL578 (ornithine cyclodeaminase), FTL663 (heat shock protein), and FTL1228 (iron-sulfur activator complex subunit SufD) have been previously described as virulence-associated factors in F. tularensis Identification of these Lon substrates has thus provided important clues for further understanding of the F. tularensis stress response and pathogenesis. The high-throughput approach developed in this study can be used for systematic identification of the Lon substrates in other prokaryotic and eukaryotic organisms.

Indexed as

Stress, PhysiologicalAnimalsCell LineDisease Models, AnimalEndopeptidase ClpFemaleFrancisella tularensisGene DeletionGenetic LociHumansMacrophagesMice, Inbred BALB CProtease LaTularemiaVirulence FactorsEndopeptidase ClpProtease LaVirulence Factors

Identifiers

PMID26902724
PMCPMC4862698
OpenAlexW2275507140

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.