Evidence map›Paper›PMID 21606185›Full record

ArticleInfection and immunity2011

The hybrid histidine kinase Hk1 is part of a two-component system that is essential for survival of Borrelia burgdorferi in feeding Ixodes scapularis ticks.

Melissa J Caimano, Melisha R Kenedy, Toru Kairu, Daniel C Desrosiers, Michael Harman, Star Dunham-Ems, Darrin R Akins, Utpal Pal, Justin D Radolf

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

75 citing papers in PubMed, 92 citations in OpenAlex.

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  19. Probing the Role ofInfection and immunity · 2021
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15 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

Melissa J CaimanoDepartment of Medicine, University of Connecticut Health Center, Farmington, CT 06030-3715, USA. mcaima@up.uchc.edu
Melisha R Kenedy
Toru Kairu
Daniel C Desrosiers
Michael Harman
Star Dunham-Ems
Darrin R Akins
Utpal Pal
Justin D Radolf
UConn Health · USUniversity of Maryland, College Park · USUniversity of Oklahoma Health Sciences Center · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI FINBERG, ROBERT WILLIAM · 2003 to 2013
$113.7M
RpoS Regulation of Borrelia burgdorferi Genes in vivoR01AI029735 · NIAID · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI CAIMANO, MELISSA J, RADOLF, JUSTIN D · 1990 to 2022
$10.7M
Outer Membrane Proteins of Borrelia burgdorferiR01AI059373 · NIAID · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI AKINS, DARRIN R. · 2005 to 2022
$4.7M
RpoS Regulation of Borrelia burgdorferi Genes in vivoR56AI029735 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI RADOLF, JUSTIN D · 2012 to 2012
$536k
Surface Lipoproteins and Serum Resistance in Borrelia burgdorferiR21AI085310 · NIAID · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI AKINS, DARRIN R. · 2010 to 2011
$402k
Outer membrane proteins of Borrelia burgdorferiR56AI059373 · NIAID · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI AKINS, DARRIN R. · 2011 to 2011
$329k
Transit of Borrelia burgdorferi through the Ixodes scapularis midgut proceeds inR03AI085248 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI CAIMANO, MELISSA J · 2010 to 2011
$153k
NIAID NIH HHS 3R01AI029735-20S1NIAID NIH HHS AI059373NIAID NIH HHS AI085248NIAID NIH HHS AI085310NIAID NIH HHS AI-29735NIAID NIH HHS R01 AI029735NIAID NIH HHS R01 AI059373NIAID NIH HHS R03 AI085248NIAID NIH HHS R21 AI085310NIAID NIH HHS R56 AI029735NIAID NIH HHS R56 AI059373NIAID NIH HHS U54 AI-057159NIAID NIH HHS U54 AI057159PHS HHS A1080615
6 · The paper itself

Abstract

Two-component systems (TCS) are principal mechanisms by which bacteria adapt to their surroundings. Borrelia burgdorferi encodes only two TCS. One is comprised of a histidine kinase, Hk2, and the response regulator Rrp2. While the contribution of Hk2 remains unclear, Rrp2 is part of a regulatory pathway involving the spirochete's alternate sigma factors, RpoN and RpoS. Genes within the Rrp2/RpoN/RpoS regulon function to promote tick transmission and early infection. The other TCS consists of a hybrid histidine kinase, Hk1, and the response regulator Rrp1. Hk1 is composed of two periplasmic sensor domains (D1 and D2), followed by conserved cytoplasmic histidine kinase core, REC, and Hpt domains. In addition to its REC domain, Rrp1 contains a GGDEF motif characteristic of diguanylate cyclases. To investigate the role of Hk1 during the enzootic cycle, we inactivated this gene in two virulent backgrounds. Extensive characterization of the resulting mutants revealed a dramatic phenotype whereby Hk1-deficient spirochetes are virulent in mice and able to migrate out of the bite site during feeding but are killed within the midgut following acquisition. We hypothesize that the phosphorelay between Hk1 and Rrp1 is initiated by the binding of feeding-specific ligand(s) to Hk1 sensor domain D1 and/or D2. Once activated, Rrp1 directs the synthesis of cyclic dimeric GMP (c-di-GMP), which, in turn, modulates the expression and/or activity of gene products required for survival within feeding ticks. In contrast to the Rrp2/RpoN/RpoS pathway, which is active only within feeding nymphs, the Hk1/Rrp1 TCS is essential for survival during both larval and nymphal blood meals.

Indexed as

Microbial ViabilityAnimalsBorrelia burgdorferiDisease Models, AnimalFemaleGene Knockout TechniquesHistidine KinaseIxodesLyme DiseaseMiceMice, Inbred C3HProtein KinasesRodent DiseasesSignal TransductionStress, PhysiologicalVirulenceHistidine KinaseProtein Kinases

Identifiers

PMID21606185
PMCPMC3147546
OpenAlexW2101665157

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.