Bacterial adherence in otitis media: Determination of N-acetylgalactosamine (GalNAc) residues in the submucosal glands and surface epithelium of the normal and diseased Eustachian tube

Kirkeby, Svend; Friis, Mogens Laue; Mikkelsen, Hanne B.; Cayé‐Thomasen, Per

doi:10.1016/j.micpath.2011.03.008

Cited by 14 publications

(14 citation statements)

References 38 publications

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“…GALNT14 belongs to a large subfamily of glycosyltransferases that catalyse the transfer of N-acetyl-D-galactosamine (GalNAc) in O-glycosylation of mucin substrates such as MUC2, MUC5AC, MUC7, and MUC13 [41]. GalNAc containing sugar residues are essential for initial adherence of respiratory bacteria epithelial cell surfaces [42]. As is the case for FBXO11 [43], which regulates anti-inflammatory TGFβ via SMAD2 [44], this could include a role in response to commensal bacteria in determining OM pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

et al. 2012

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BackgroundOtitis media (OM) is a common childhood disease characterised by middle ear inflammation and effusion. Susceptibility to recurrent acute OM (rAOM; ≥3 episodes of AOM in 6 months) and chronic OM with effusion (COME; MEE ≥3 months) is 40–70% heritable. Few underlying genes have been identified to date, and no genome-wide association study (GWAS) of OM has been reported.Methods and FindingsData for 2,524,817 single nucleotide polymorphisms (SNPs; 535,544 quality-controlled SNPs genotyped by Illumina 660W-Quad; 1,989,273 by imputation) were analysed for association with OM in 416 cases and 1,075 controls from the Western Australian Pregnancy Cohort (Raine) Study. Logistic regression analyses under an additive model undertaken in GenABEL/ProbABEL adjusting for population substructure using principal components identified SNPs at CAPN14 (rs6755194: OR = 1.90; 95%CI 1.47–2.45; Padj-PCA = 8.3×10−7) on chromosome 2p23.1 as the top hit, with independent effects (rs1862981: OR = 1.60; 95%CI 1.29–1.99; Padj-PCA = 2.2×10−5) observed at the adjacent GALNT14 gene. In a gene-based analysis in VEGAS, BPIFA3 (PGene = 2×10−5) and BPIFA1 (PGene = 1.07×10−4) in the BPIFA gene cluster on chromosome 20q11.21 were the top hits. In all, 32 genomic regions show evidence of association (Padj-PCA<10−5) in this GWAS, with pathway analysis showing a connection between top candidates and the TGFβ pathway. However, top and tag-SNP analysis for seven selected candidate genes in this pathway did not replicate in 645 families (793 affected individuals) from the Western Australian Family Study of Otitis Media (WAFSOM). Lack of replication may be explained by sample size, difference in OM disease severity between primary and replication cohorts or due to type I error in the primary GWAS.ConclusionsThis first discovery GWAS for an OM phenotype has identified CAPN14 and GALNT14 on chromosome 2p23.1 and the BPIFA gene cluster on chromosome 20q11.21 as novel candidate genes which warrant further analysis in cohorts matched more precisely for clinical phenotypes.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

et al. 2012

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“…106,107 Increased GalNAc residues are present along the eustachian tube and in submucosal serous glands during infection and may serve as receptors for adherence. 73,108 …”

Section: Discussionmentioning

confidence: 99%

Panel 4: Report of the Microbiology Panel

Barenkamp

Chonmaitree

Håkansson

et al. 2017

Otolaryngol.--head neck surg.

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Objective To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.

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“…Early in 1992, there have been studies indicating removal of sialic acid residues from the salivary mucin preventing adherence of Streptococcus sanguis, suggesting that this saccharide mediates binding and play an important role in governing bacterial adherence [26]. Researches from Kirkeby [11] showed that GalNAc residues increased in both the submucosal serous glands and in the surface epithelium of the eustachian tube after middle ear infection with S. pneumonia, which may be important in relation to subsequent formation of a bacterial biofilm in the middle ear. Another study from Lorwai Tan [27], observed a strong positive correlation between the aberrant terminal sugar patterns in this subgroup of CRS patients with biofilms formation.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients

Mao¹,

Chen²,

Wang³

et al. 2015

Auris Nasus Larynx

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Bacterial adherence in otitis media: Determination of N-acetylgalactosamine (GalNAc) residues in the submucosal glands and surface epithelium of the normal and diseased Eustachian tube

Cited by 14 publications

References 38 publications

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

Panel 4: Report of the Microbiology Panel

Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients

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