Evidence map›Paper›PMID 25936376›Full record

ArticleApplied microbiology and biotechnology2015

Targeting surface-layer proteins with single-domain antibodies: a potential therapeutic approach against Clostridium difficile-associated disease.

Hiba Kandalaft, Greg Hussack, Annie Aubry, Henk van Faassen, Yonghong Guan, Mehdi Arbabi-Ghahroudi, Roger MacKenzie, Susan M Logan, Jamshid Tanha

Open access · hybridAbstract read
In one paragraph

Article in Applied microbiology and biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

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  13. TargetingFrontiers in microbiology · 2018
    Review
  14. Article
  15. Clostridium difficile infection.Nature reviews. Disease primers · 2016
    Review
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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

9 authors at 2 institutions in 1 country.

Hiba KandalaftHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Greg HussackHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Annie AubryHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Henk van FaassenHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Yonghong GuanHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Mehdi Arbabi-GhahroudiHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Roger MacKenzieHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Susan M LoganHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Jamshid TanhaHuman Health Therapeutics Portfolio, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada. jamshid.tanha@nrc-cnrc.gc.ca.
National Research Council Canada · CAUniversity of Guelph · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clostridium difficile is a leading cause of death from gastrointestinal infections in North America. Antibiotic therapy is effective, but the high incidence of relapse and the rise in hypervirulent strains warrant the search for novel treatments. Surface layer proteins (SLPs) cover the entire C. difficile bacterial surface, are composed of high-molecular-weight (HMW) and low-molecular-weight (LMW) subunits, and mediate adherence to host cells. Passive and active immunization against SLPs has enhanced hamster survival, suggesting that antibody-mediated neutralization may be an effective therapeutic strategy. Here, we isolated a panel of SLP-specific single-domain antibodies (VHHs) using an immune llama phage display library and SLPs isolated from C. difficile hypervirulent strain QCD-32g58 (027 ribotype) as a target antigen. Binding studies revealed a number of VHHs that bound QCD-32g58 SLPs with high affinity (K D = 3-6 nM) and targeted epitopes located on the LMW subunit of the SLP. The VHHs demonstrated melting temperatures as high as 75 °C, and a few were resistant to the gastrointestinal protease pepsin at physiologically relevant concentrations. In addition, we demonstrated the binding specificity of the VHHs to the major C. difficile ribotypes by whole cell ELISA, where all VHHs were found to bind 001 and 027 ribotypes, and a subset of antibodies were found to be broadly cross-reactive in binding cells representative of 012, 017, 023, and 078 ribotypes. Finally, we showed that several of the VHHs inhibited C. difficile QCD-32g58 motility in vitro. Targeting SLPs with VHHs may be a viable therapeutic approach against C. difficile-associated disease.

Indexed as

Anti-Bacterial AgentsAntibodies, BacterialBacterial ProteinsClostridioides difficileEpitopesLocomotionMembrane GlycoproteinsPeptide LibraryProtein BindingSingle-Domain AntibodiesAnti-Bacterial AgentsAntibodies, BacterialBacterial ProteinsEpitopesMembrane GlycoproteinsPeptide LibrarySingle-Domain AntibodiesS-layer proteinsClostridium difficileNanobodySingle-domain antibodySurface layer proteinVHH

Identifiers

PMID25936376
PMCPMC4768215
OpenAlexW1983387742

What OpenQuestion holds

Textmetadata
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.