Evidence map›Paper›PMID 35367613›Full record

ArticleAnaerobe2022

Identification of Clostridium innocuum hypothetical protein that is cross-reactive with C. difficile anti-toxin antibodies.

K E Cherny, A Balaji, J Mukherjee, Y A Goo, A R Hauser, E Ozer, K J F Satchell, K E R Bachta, T J Kochan, S D Mitra and 1 more

Open access · greenAbstract read
In one paragraph

Article in Anaerobe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Co-Colonization of Non-Antibiotics (Basel, Switzerland) · 2025
    Article
  3. Article
  4. Virulence · 2023
    Article
  5. Article
  6. Association Between Clostridium innocuum and Antibiotic-Associated Diarrhea in Adults and Children: A Cross-sectional Study and Comparative Genomics Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Article
  7. Can Clostridium innocuum Masquerade as Clostridioides difficile?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    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

11 authors at 2 institutions in 1 country.

K E ChernyAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. Electronic address: kcherny@luriechildrens.org.
A BalajiAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
J MukherjeeAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Y A GooNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA.
A R HauserNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA.
E OzerNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA.
K J F SatchellNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA; Center for Structural Genomics of Infectious Diseases, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
K E R BachtaNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA.
T J KochanNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA.
S D MitraNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA.
L K KociolekAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Northwestern University · USLurie Children's Hospital · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9M
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
TR&D 7: Cell Specific ProteomicsP41GM108569 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2015 to 2024
$13.6M
Acquisition of a Thermo Fisher Scientific Q Exactive UHMR mass spectrometerS10OD025194 · OD · NORTHWESTERN UNIVERSITY · PI COMPTON, PHILIP DANIEL · 2018 to 2018
$795k
Clostridium innocuum as an emerging multidrug-resistant antibiotic-associated diarrheal pathogenR21AI144549 · NIAID · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI KOCIOLEK, LARRY K · 2019 to 2020
$440k
NCATS NIH HHS UL1 TR001422NCI NIH HHS P30 CA060553NIAID NIH HHS HHSN272201700060CNIAID NIH HHS R21 AI144549NIGMS NIH HHS P41 GM108569NIH HHS S10 OD025194
6 · The paper itself

Abstract

objectivesPreviously considered solely an opportunistic pathogen, Clostridium innocuum (CI) was recently reported in Taiwan to be an emerging cause of antibiotic-associated diarrhea and clinically indistinguishable from Clostridioides difficile (CD) infection. We previously identified CI culture supernatant being cross-reactive with commercial CD toxin enzyme immunoassays. We aimed to identify and characterize the cross-reacting protein and determine whether it functioned as a human toxin.

methodsWe performed western blots using CI culture supernatants and CD anti-toxin antibodies and identified interacting bands. We identified protein(s) using tandem mass spectrometry and evaluated them by cytotoxicity assays.

resultsCI, but not CD, was isolated from stool of 12 children and adults with diarrhea. Culture supernatant from 6/12 CI isolates, and an ATCC reference strain, tested positive for CD toxins (total 7/13 isolates) by commercial EIA. Using two of these isolates, we identified two ∼40 kDa hypothetical proteins, CI_01447 and CI_01448, and confirmed cross-reactivity with CD anti-toxin antibodies by enzyme immunoassay and Western blot. Whole-genome sequencing confirmed all 13 isolates contained both genes, which were highly conserved. We observed no cytopathic or cytotoxic effects to HeLa cells when treated with these proteins. We identified amino acid sequence similarity to the NlpC/P60 family of proteins.

conclusionsOur findings do not suggest CI proteins CI_01448 and CI_01447, which cross-react with antibodies against CD toxins A and B, are toxic to HeLa cells. Further studies are needed to determine the function of these cross-reacting proteins and the potential virulence factors that could be responsible for CI diarrheal disease.

Indexed as

Bacterial ToxinsClostridioides difficileClostridium InfectionsAdultBacillotaBacterial ProteinsChildDiarrheaEnterotoxinsFecesHeLa CellsHumansBacterial ProteinsBacterial ToxinsEnterotoxinsAntibiotic-associated diarrheaClostridioides difficileClostridium innocuumNlpC/P60Toxin AToxin B

Identifiers

PMID35367613
PMCPMC9197939
OpenAlexW4220721257

What OpenQuestion holds

Textmetadata
LicenceTDM
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.