Evidence map›Paper›PMID 32716926›Full record

ArticlePLoS genetics2020

IgaA negatively regulates the Rcs Phosphorelay via contact with the RcsD Phosphotransfer Protein.

Erin A Wall, Nadim Majdalani, Susan Gottesman

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.9field-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

40 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Structural and functional insights into the Rcs phosphorelay.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
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  5. Review
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  8. Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  14. Survival and genomic stability ofFrontiers in cellular and infection microbiology · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Cyclic Isothiocyanate Goitrin ImpairsPlants (Basel, Switzerland) · 2024
    Article
  19. Article
  20. RcsF-independent mechanisms of signaling within the Rcs Phosphorelay.bioRxiv : the preprint server for biology · 2024
    Article
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

3 authors at 1 institution in 1 country.

Erin A WallNational Cancer Institute, Bethesda, Maryland, United States of America.
Nadim MajdalaniNational Cancer Institute, Bethesda, Maryland, United States of America.
Susan GottesmanNational Cancer Institute, Bethesda, Maryland, United States of America.ORCID 0000-0002-7792-1284
National Cancer Institute · US

Funding

Bacterial Functions Involved in Cell Growth ControlZIABC008714 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GOTTESMAN, SUSAN · 2009 to 2025
$20.3M
The Rcs phosphorelay is a crucial drug target for abrogation of virulent capsule formation in Klebsiella pneumoniae and other Carbapenem-resistant Enterobacteriaceae (CRE)FI2GM123943 · NIGMS · NATIONAL CANCER INSTITUTE · PI WALL, ERIN ASHLEY · 2017 to 2017
–
NIGMS NIH HHS FI2 GM123943
6 · The paper itself

Abstract

Two-component systems and phosphorelays play central roles in the ability of bacteria to rapidly respond to changing environments. In E. coli and related enterobacteria, the complex Rcs phosphorelay is a critical player in the bacterial response to antimicrobial peptides, beta-lactam antibiotics, and other disruptions at the cell surface. The Rcs system is unusual in that an inner membrane protein, IgaA, is essential due to its negative regulation of the RcsC/RcsD/RcsB phosphorelay. While it is known that IgaA transduces signals from the outer membrane lipoprotein RcsF, how it interacts with the phosphorelay has remained unknown. Here we performed in vivo interaction assays and genetic dissection of the critical proteins and found that IgaA interacts with the phosphorelay protein RcsD, and that this interaction is necessary for regulation. Interactions between IgaA and RcsD within their respective periplasmic domains of these two proteins anchor repression of signaling. However, the signaling response depends on a second interaction between cytoplasmic loop 1 of IgaA and a truncated Per-Arndt-Sim (PAS-like) domain in RcsD. A single point mutation in the PAS-like domain increased interactions between the two proteins and blocked induction of the phosphorelay. IgaA may regulate RcsC, the histidine kinase that initiates phosphotransfer through the phosphorelay, indirectly, via its contacts with RcsD. Unlike RcsD, and unlike many other histidine kinases, the periplasmic domain of RcsC is dispensable for the response to signals that induce the Rcs phosphorelay system. The multiple contacts between IgaA and RcsD constitute a poised sensing system, preventing potentially toxic over-activation of this phosphorelay while enabling it to rapidly and quantitatively respond to signals.

Indexed as

Escherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialMembrane ProteinsMultienzyme ComplexesPhosphoproteinsPhosphorylationPhosphotransferasesProtein TransportSalmonella typhimuriumSignal TransductionEscherichia coli ProteinsIgaA protein, E coliIgaA protein, Salmonella typhimuriumMembrane ProteinsMultienzyme ComplexesPhosphoproteinsPhosphotransferasesrcsD protein, E colircsF protein, E coli

Identifiers

PMID32716926
PMCPMC7418988
OpenAlexW3045084911

What OpenQuestion holds

Textmetadata
LicenceCC0
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.