Evidence map›Paper›PMID 35475643›Full record

ArticlemBio2022

Bma-LAD-2, an Intestinal Cell Adhesion Protein, as a Potential Therapeutic Target for Lymphatic Filariasis.

Alexander F Flynn, Rebekah T Taylor, Marzena E Pazgier, Sasisekhar Bennuru, Alyssa R Lindrose, Spencer L Sterling, C Paul Morris, Brynna I Gleeson, Tim K Maugel, Thomas B Nutman and 1 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 51% 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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 5 institutions in 1 country.

Alexander F FlynnDepartment of Microbiology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.ORCID 0000-0002-0348-8983
Rebekah T TaylorDepartment of Biology, Frostburg State Universitygrid.256103.3, Frostburg, Maryland, USA.ORCID 0000-0003-3601-5346
Marzena E PazgierDepartment of Medicine, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.ORCID 0000-0003-0594-5057
Sasisekhar BennuruNational Institute of Allergy and Infectious Disease, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA.
Alyssa R LindroseDepartment of Microbiology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.
Spencer L SterlingDepartment of Microbiology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.
C Paul MorrisDepartment of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Brynna I GleesonDepartment of Microbiology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.
Tim K MaugelLaboratory for Biological Ultrastructure, Department of Biology, University of Maryland, Silver Spring, Maryland, USA.
Thomas B NutmanNational Institute of Allergy and Infectious Disease, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA.ORCID 0000-0001-6887-4941
Edward MitreDepartment of Microbiology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.ORCID 0000-0001-7506-3266
Uniformed Services University of the Health Sciences · USNational Institutes of Health · USFrostburg State University · USHenry M. Jackson Foundation · USJohns Hopkins Hospital · US

Funding

Molecular Definition Of Filarial And Related Nonfilarial Genes And ProteinsZIAAI000512 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NUTMAN, THOMAS · 2009 to 2025
$9.9M
6 · The paper itself

Abstract

Lymphatic filariasis is a debilitating disease that afflicts over 70 million people worldwide. It is caused by the parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Despite substantial success, efforts to eliminate LF will likely require more time and resources than predicted. Identifying new drug and vaccine targets in adult filariae could help elimination efforts. This study's aim was to evaluate intestinal proteins in adult Brugia malayi worms as possible therapeutic targets. Using short interfering RNA (siRNA), we successfully targeted four candidate gene transcripts: Bma-Serpin, Bma-ShTK, Bma-Reprolysin, and Bma-LAD-2. Of those, Bma-LAD-2, an immunoglobulin superfamily cell adhesion molecule (IgSF CAM), was determined to be essential for adult worm survival. We observed a 70.42% knockdown in Bma-LAD-2 transcript levels 1 day post-siRNA incubation and an 87.02% reduction in protein expression 2 days post-siRNA incubation. This inhibition of Bma-LAD-2 expression resulted in an 80% decrease in worm motility over 6 days, a 93.43% reduction in microfilaria release (Mf) by day 6 post-siRNA incubation, and a dramatic decrease in (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Transmission electron microscopy revealed the loss of microvilli and unraveling of mitochondrial cristae in the intestinal epithelium of Bma-LAD-2 siRNA-treated worms. Strikingly, Bma-LAD-2 siRNA-treated worms exhibited an almost complete loss of pseudocoelomic fluid. A luciferase immunoprecipitation system assay did not detect anti-Bma-LAD-2 IgE in the serum of 30 LF patients, indicating that LF exposure does not result in IgE sensitization to this antigen. These results indicate that Bma-LAD-2 is an essential protein for adult Brugia malayi and may be an effective therapeutic target.

Indexed as

Brugia malayiCell Adhesion MoleculesElephantiasis, FilarialHelminth ProteinsAnimalsCell AdhesionHumansImmunoglobulin ERNA, Small InterferingCell Adhesion MoleculesHelminth ProteinsImmunoglobulin ERNA, Small InterferingBrugia malayiBrugia pahangiBrugia timorifilariafilariasishelminthneglected tropical diseasessiRNAvaccineWuchereria bancrofti

Identifiers

PMID35475643
PMCPMC9239158
OpenAlexW4226229849

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.