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

Abstract

ObjectivesWe 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.MethodsSinus 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.ResultsNineteen 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.ConclusionsAbundant 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.Level of EvidenceNot applicable Laryngoscope, 2023