Evidence map›Paper›PMID 35618711›Full record

ArticleNature communications2022

Transgenic Anopheles mosquitoes expressing human PAI-1 impair malaria transmission.

Tales V Pascini, Yeong Je Jeong, Wei Huang, Zarna R Pala, Juliana M Sá, Michael B Wells, Christopher Kizito, Brendan Sweeney, Thiago L Alves E Silva, Deborah J Andrew and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. 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
3.7field-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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  13. Peptides with Antimicrobial Activity in the Saliva of the Malaria VectorInternational journal of molecular sciences · 2024
    Article
  14. Article
  15. bioRxiv : the preprint server for biology · 2023
    Article
  16. Review
  17. 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

12 authors at 2 institutions in 1 country.

Tales V PasciniLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA.
Yeong Je JeongLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA.
Wei HuangDepartment of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Zarna R PalaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA.
Juliana M SáLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA.ORCID http://orcid.org/0000-0003-3813-8104
Michael B WellsDepartment of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, G10 Hunterian, Baltimore, MD, 21205, USA.
Christopher KizitoDepartment of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Brendan SweeneyLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA.
Thiago L Alves E SilvaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA.
Deborah J AndrewDepartment of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, G10 Hunterian, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0003-1051-6935
Marcelo Jacobs-LorenaDepartment of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Joel Vega-RodríguezLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rm 2E20A, Rockville, MD, 20852, USA. joel.vega-rodriguez@nih.gov.ORCID http://orcid.org/0000-0002-9576-0058
National Institutes of Health · USJohns Hopkins University · US

Funding

ZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI BELCHER, HAROLYN MILLICENT EDITH · 1985 to 2007
$37.3M
Malaria Drug Resistance and Disease VirulenceZIAAI000483 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WELLEMS, THOMAS E · 2009 to 2025
$24.5M
FORMATION OF THE DROSOPHILA SALIVARY GLANDR01DE013899 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI Deborah J Andrew · 2001 to 2026
$11.2M
Host-parasite-vector interactions during malaria transmissionZIAAI001250 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI VEGA-RODRIGUEZ, JOEL · 2019 to 2025
$9.9M
Targeting mosquito organs with phage display librariesR01AI031478 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JACOBS-LORENA, MARCELO · 1991 to 2018
$6.0M
Molecular mechanisms of Plasmodium fertilizationR01AI127405 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JACOBS-LORENA, MARCELO · 2017 to 2021
$2.0M
Generation of transmission-compromised mosquitoesR21AI153588 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ANDREW, DEBORAH J · 2020 to 2021
$450k
NCRR NIH HHS M01 RR000052NIAID NIH HHS R01 AI031478NIAID NIH HHS R01 AI127405NIAID NIH HHS R21 AI153588NIDCR NIH HHS R01 DE013899
6 · The paper itself

Abstract

In mammals, the serine protease plasmin degrades extracellular proteins during blood clot removal, tissue remodeling, and cell migration. The zymogen plasminogen is activated into plasmin by two serine proteases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), a process regulated by plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor that specifically inhibits tPA and uPA. Plasmodium gametes and sporozoites use tPA and uPA to activate plasminogen and parasite-bound plasmin degrades extracellular matrices, facilitating parasite motility in the mosquito and the mammalian host. Furthermore, inhibition of plasminogen activation by PAI-1 strongly blocks infection in both hosts. To block parasite utilization of plasmin, we engineered Anopheles stephensi transgenic mosquitoes constitutively secreting human PAI-1 (huPAI-1) in the midgut lumen, in the saliva, or both. Mosquitoes expressing huPAI-1 strongly reduced rodent and human Plasmodium parasite transmission to mosquitoes, showing that co-opting plasmin for mosquito infection is a conserved mechanism among Plasmodium species. huPAI-1 expression in saliva induced salivary gland deformation which affects sporozoite invasion and P. berghei transmission to mice, resulting in significant levels of protection from malaria. Targeting the interaction of malaria parasites with the fibrinolytic system using genetically engineered mosquitoes could be developed as an intervention to control malaria transmission.

Indexed as

AnophelesMalariaPlasmodiumAnimalsAnimals, Genetically ModifiedFibrinolysinHumansMammalsMiceMosquito VectorsPlasminogenPlasminogen Activator Inhibitor 1SporozoitesFibrinolysinPlasminogenPlasminogen Activator Inhibitor 1

Identifiers

PMID35618711
PMCPMC9135733
OpenAlexW4281563653

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.