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

Llwyatt K Hofer1, Joseph A Jurcisek1, Charles Elmaraghy2,3,4

  • 1Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, U.S.A.

The Laryngoscope
|August 19, 2023
PubMed
Abstract

Insights

Pediatric chronic rhinosinusitis (CRS) samples showed abundant Z-form extracellular DNA (eDNA). Bacterial DNABII proteins likely convert B-DNA to Z-form eDNA, potentially causing persistent CRS.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Chronic rhinosinusitis (CRS) is a prevalent condition with complex pathogenesis.
  • Extracellular DNA (eDNA) plays a role in bacterial biofilm formation and host immune response.
  • Z-form DNA is a rare DNA conformation with implications in cellular processes.

Purpose of the Study:

  • To investigate the presence and form of eDNA in pediatric CRS.
  • To identify bacterial DNABII proteins involved in DNA conformation.
  • To explore the role of Z-form eDNA in CRS pathogenesis.

Main Methods:

  • Sinus mucosal samples from 20 pediatric CRS patients were analyzed.
  • Immunolabeling was used to detect B-DNA, Z-DNA, and bacterial DNABII proteins (IHF and HU).
  • Samples were obtained during functional endoscopic sinus surgery (FESS).

Main Results:

  • Ninety-five percent of samples (19/20) contained eDNA, predominantly in the Z-form.
  • B-DNA was mainly found in distal mucosal regions.
  • DNABII proteins were detected on both B- and Z-DNA, confirming their role in B-to-Z DNA conversion.

Conclusions:

  • Abundant Z-form eDNA in pediatric CRS suggests bacterial DNABII proteins convert released eukaryotic B-DNA to Z-form.
  • This conversion may stabilize bacterial biofilms and evade host defenses (NETosis).
  • The findings hypothesize that Z-form eDNA contributes to the chronicity and treatment resistance of CRS.
Keywords:
BiofilmDNABII ProteinsFESSPMNs

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