Evidence map›Paper›PMID 41349531›Full record

ArticleCell reports2025

Allele-specific zinc metalloprotease B influences cardiac damage during invasive pneumococcal disease.

Jennifer N Luck, Adonis D'Mello, Vipin Chembilikandy, Jessica R Lane, Katherine Kruckow, Eriel Martínez, Efrain Rodriguez, Mohammed Mohasin, Ian Berg, Katherine D Porter and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. 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
–field-weighted citation impact
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.

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

13 authors.

Jennifer N LuckDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Adonis D'MelloInstitute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
Vipin ChembilikandyDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Jessica R LaneDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Katherine KruckowDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Eriel MartínezDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Efrain RodriguezDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Mohammed MohasinDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Ian BergDivision of Cardiovascular Diseases, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Katherine D PorterDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Palanappian SethuDivision of Cardiovascular Diseases, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Hervé TettelinInstitute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
Carlos J OrihuelaDepartment of Microbiology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: corihuel@uab.edu.

Funding

Cardiac microlesion formation during invasive pneumococcal diseaseR01AI114800 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Carlos J Orihuela, Herve S TETTELIN · 2015 to 2026
$5.1M
Molecular mechanisms underlying organ penetration in disseminated pneumococcal infectionR01AI172796 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Carlos J Orihuela, Min Xie · 2023 to 2026
$2.6M
NIAID NIH HHS R01 AI114800NIAID NIH HHS R01 AI172796
6 · The paper itself

Abstract

During severe infection, Streptococcuspneumoniae invades the myocardium, causing life-threatening cardiac complications. Bacterial genome-wide association studies implicate a specific allele of the gene encoding zinc metalloprotease B (ZmpB) as a key determinant of S. pneumoniae-mediated cardiac damage. In mouse models, ZmpB-deficient S. pneumoniae show reduced cardiac microlesion formation, and immunization with recombinant ZmpB confers protection. ZmpB-deficient S. pneumoniae are also attenuated in their ability to impair contractility of human induced pluripotent stem cell (iPSC)-derived 3D cardiac organoids and exhibit reduced invasion and intracellular survival in mouse cardiac vascular endothelial cell (MCEC) and atrial cardiomyocyte (HL-1) cell lines. ZmpB varies in the number of FIVAR (found in various architectures) domains at its N terminus, with FIVAR-rich variants being prevalent in strains linked to human cardiac complications. Using clinical isolates and isogenic mutants producing ZmpB with different FIVAR domain counts, we confirm this association. These findings indicate that FIVAR-rich ZmpB variants enhance S. pneumoniae's invasive capacity, increasing the risk of cardiac pathology.

Indexed as

Bacterial ProteinsMetalloproteasesMyocardiumPneumococcal InfectionsStreptococcus pneumoniaeAllelesAnimalsCell LineEndothelial CellsHumansInduced Pluripotent Stem CellsMiceMice, Inbred C57BLMyocytes, CardiacOrganoidsBacterial ProteinsMetalloproteasesbGWAScardiac microlesionsCP: immunologyCP: microbiologyFIVARintracellular bacteriainvasive pneumococcal diseasemajor adverse cardiac eventsStreptococcus pneumoniaezinc metalloproteasesZmpB

Identifiers

PMID41349531
PMCPMC13112766

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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.