Z-Form Extracellular DNA in Pediatric CRS May Provide a Mechanism for Recalcitrance to Treatment.


Journal

The Laryngoscope
ISSN: 1531-4995
Titre abrégé: Laryngoscope
Pays: United States
ID NLM: 8607378

Informations de publication

Date de publication:
Apr 2024
Historique:
revised: 21 07 2023
received: 19 05 2023
accepted: 09 08 2023
pmc-release: 19 02 2025
medline: 18 3 2024
pubmed: 19 8 2023
entrez: 19 8 2023
Statut: ppublish

Résumé

We examined sinus mucosal samples recovered from pediatric chronic rhinosinusitis (CRS) patients for the presence of Z-form extracellular DNA (eDNA) due to its recently elucidated role in pathogenesis of disease. Further, we immunolabeled these specimens for the presence of both members of the bacterial DNA-binding DNABII protein family, integration host factor (IHF) and histone-like protein (HU), due to their known role in converting common B-DNA to the rare Z-form. Sinus mucosa samples recovered from 20 patients during functional endoscopic sinus surgery (FESS) were immunolabelled for B- and Z-DNA, as well as for both bacterial DNABII proteins. Nineteen of 20 samples (95%) included areas rich in eDNA, with the majority in the Z-form. Areas positive for B-DNA were restricted to the most distal regions of the mucosal specimen. Labeling for both DNABII proteins was observed on B- and Z-DNA, which aligned with the role of these proteins in the B-to-Z DNA conversion. Abundant Z-form eDNA in culture-positive pediatric CRS samples suggested that bacterial DNABII proteins were responsible for the conversion of eukaryotic B-DNA that had been released into the luminal space by PMNs during NETosis, to the Z-form. The presence of both DNABII proteins on B-DNA and Z-DNA supported the known role of these bacterial proteins in the B-to-Z DNA conversion. Given that Z-form DNA both stabilizes the bacterial biofilm and inactivates PMN NET-mediated killing of trapped bacteria, we hypothesize that this conversion may be contributing to the chronicity and recalcitrance of CRS to treatment. NA Laryngoscope, 134:1564-1571, 2024.

Identifiants

pubmed: 37597166
doi: 10.1002/lary.30986
pmc: PMC10875147
mid: NIHMS1932891
doi:

Substances chimiques

DNA, Z-Form 0
DNA, B-Form 0
Integration Host Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1564-1571

Subventions

Organisme : NIDCD NIH HHS
ID : R01 DC003915
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC011818
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC003915
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC011818
Pays : United States

Informations de copyright

© 2023 The American Laryngological, Rhinological and Otological Society, Inc.

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Auteurs

Llwyatt K Hofer (LK)

Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

Joseph A Jurcisek (JA)

Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

Charles Elmaraghy (C)

The Ohio State University College of Medicine, Columbus, Ohio, U.S.A.
Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, U.S.A.
Department of Pediatric Otolaryngology, Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

Steven D Goodman (SD)

Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.
The Ohio State University College of Medicine, Columbus, Ohio, U.S.A.

Lauren O Bakaletz (LO)

Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.
The Ohio State University College of Medicine, Columbus, Ohio, U.S.A.

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