Evidence map›Paper›PMID 31648246›Full record

ArticlePloS one2019

Stringent response governs the oxidative stress resistance and virulence of Francisella tularensis.

Zhuo Ma, Kayla King, Maha Alqahtani, Madeline Worden, Parthasarathy Muthuraman, Christopher L Cioffi, Chandra Shekhar Bakshi, Meenakshi Malik

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  4. Journal of bacteriology · 2025
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  10. Diverse roles of low-molecular weight thiol GSH inCurrent research in microbial sciences · 2024
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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 2 institutions in 1 country.

Zhuo MaDepartment of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.
Kayla KingDepartment of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.
Maha AlqahtaniDepartment of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America.
Madeline WordenDepartment of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.
Parthasarathy MuthuramanDepartment of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.
Christopher L CioffiDepartment of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.
Chandra Shekhar BakshiDepartment of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America.
Meenakshi MalikDepartment of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.ORCID 0000-0003-0051-4485
Albany College of Pharmacy and Health Sciences · USNew York Medical College · US

Funding

Repression of Inflammasome by Francisella tularensisR15AI107698 · NIAID · ALBANY COLLEGE OF PHARMACY · PI MALIK, MEENAKSHI · 2013 to 2024
$1.9M
Modulation of host innate immune response by Francisella tularensisR56AI101109 · NIAID · NEW YORK MEDICAL COLLEGE · PI BAKSHI, CHANDRA SHEKHAR · 2013 to 2013
$390k
Modulation of macrophage function by Francisella tularensisR56AI090072 · NIAID · NEW YORK MEDICAL COLLEGE · PI BAKSHI, CHANDRA SHEKHAR · 2010 to 2010
$316k
NIAID NIH HHS R15 AI107698NIAID NIH HHS R56 AI090072NIAID NIH HHS R56 AI101109
6 · The paper itself

Abstract

Francisella tularensis is a Gram-negative bacterium responsible for causing tularemia in the northern hemisphere. F. tularensis has long been developed as a biological weapon due to its ability to cause severe illness upon inhalation of as few as ten organisms and, based on its potential to be used as a bioterror agent is now classified as a Tier 1 Category A select agent by the CDC. The stringent response facilitates bacterial survival under nutritionally challenging starvation conditions. The hallmark of stringent response is the accumulation of the effector molecules ppGpp and (p)ppGpp known as stress alarmones. The relA and spoT gene products generate alarmones in several Gram-negative bacterial pathogens. RelA is a ribosome-associated ppGpp synthetase that gets activated under amino acid starvation conditions whereas, SpoT is a bifunctional enzyme with both ppGpp synthetase and ppGpp hydrolase activities. Francisella encodes a monofunctional RelA and a bifunctional SpoT enzyme. Previous studies have demonstrated that stringent response under nutritional stresses increases expression of virulence-associated genes encoded on Francisella Pathogenicity Island. This study investigated how stringent response governs the oxidative stress response of F. tularensis. We demonstrate that RelA/SpoT-mediated ppGpp production alters global gene transcriptional profile of F. tularensis in the presence of oxidative stress. The lack of stringent response in relA/spoT gene deletion mutants of F. tularensis makes bacteria more susceptible to oxidants, attenuates survival in macrophages, and virulence in mice. This work is an important step forward towards understanding the complex regulatory network underlying the oxidative stress response of F. tularensis.

Indexed as

Oxidative StressVirulenceAnimalsBacterial ProteinsFrancisella tularensisGene Expression Regulation, BacterialLigasesMacrophagesMiceMice, Inbred C57BLRibosomesTularemiaBacterial Proteinsguanosine 3',5'-polyphosphate synthetasesLigases

Identifiers

PMID31648246
PMCPMC6812791
OpenAlexW2981353467

What OpenQuestion holds

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LicenceCC BY
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.