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Published on: December 14, 2019
Antibiotic modulation of mucins in otitis media; should this change our approach to watchful waiting?
Wenzhou Hong1, Pawjai Khampang1, Abigail R Kerschner1
1Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, USA.
Background:
Gel-forming mucins (GFMs) play important roles in otitis media (OM) pathogenesis. Increased mucin expression is activated by pathogens and proinflammatory cytokines. Bacterial biofilms influence inflammation and resolution of OM and may contribute to prolonged mucin production. The influence of specific pathogens on mucin expression and development of chronic OM with effusion (OME) remains an area of significant knowledge deficit.
Objectives:
To assess the relationship between GFM expression, specific pathogens, middle ear mucosal (MEM) changes, biofilm formation, and antibiotic utilization.
Methods:
Mixed gender chinchillas were inoculated with nontypeable Haemophilus influenzae (NTHi) strain 86028NP or Streptococcus pneumoniae (SP) strain TIGR4 via transbulla injection. Antibiotic was administered on day 3-5 post inoculation. GFM expression was measured by quantitative PCR. Biofilm formation was identified and middle ear histologic changes were measured.
Results:
SP infection resulted in higher incidence of biofilm and ME effusion compared with NTHi infection. However, NTHi persisted in the ME longer than SP with no substantive bacterial clearance detected on day 10 compared with complete bacterial clearance on day 10 for 50-60% of the SP-infected chinchillas. Both infections increased MEM inflammatory cell infiltration and thickening. NTHi upregulated the Muc5AC, Muc5B and Muc19 expression on day 10 (p = 0.0004, 0.003, and 0.002 respectively). SP-induced GFM upregulations were trended toward significant. In both NTHi and SP infections, the degree of GFM upregulation had a direct relationship to increased MEM hypertrophy, inflammatory cell infiltration and biofilm formation. Antibiotic treatment reduced the incidence of ME effusion and biofilm, limited the MEM changes and reversed the GFM upregulation. In NTHi infection, the rate of returning to baseline level of GFMs in treated chinchillas was quicker than those without treatment.
Conclusions:
In an animal model of OM, GFM genes are upregulated in conjunction with MEM hypertrophy and biofilm formation. This upregulation is less robust and more quickly ameliorated to a significant degree in the NTHi infection with appropriate antibiotic therapy. These findings contribute to the understanding of pathogen specific influences on mucin expression during OM pathogenesis and provide new data which may have implications in clinical approach for OM treatment.
Insights
Gel-forming mucins (GFMs) increase with otitis media (OM) and bacterial biofilms. Antibiotic treatment effectively reduces mucin production and middle ear changes in this animal model.
Area of Science:
- Otolaryngology
- Microbiology
- Pathogenesis
Background:
- Gel-forming mucins (GFMs) are implicated in otitis media (OM) pathogenesis.
- Bacterial biofilms and pathogens contribute to inflammation and prolonged mucin production in OM.
- The specific impact of pathogens on mucin expression and chronic OM with effusion (OME) requires further investigation.
Purpose of the Study:
- To investigate the relationship between GFM expression, specific pathogens, middle ear mucosal changes, biofilm formation, and antibiotic use.
- To understand pathogen-specific influences on mucin expression during OM.
Main Methods:
- Chinchillas were infected with nontypeable Haemophilus influenzae (NTHi) or Streptococcus pneumoniae (SP).
- Antibiotic treatment was administered post-infection.
- GFM expression was quantified using qPCR, and middle ear mucosal changes and biofilm formation were assessed histologically.
Main Results:
- SP infection led to more biofilm and middle ear effusion than NTHi.
- NTHi persisted longer in the middle ear, while SP showed significant bacterial clearance.
- Both pathogens increased middle ear mucosal inflammation and thickening; NTHi significantly upregulated Muc5AC, Muc5B, and Muc19.
- GFM upregulation correlated with middle ear hypertrophy, inflammation, and biofilm formation.
- Antibiotic treatment reduced effusion, biofilm, and mucosal changes, and reversed GFM upregulation, with faster GFM normalization in NTHi-infected, treated animals.
Conclusions:
- GFM genes are upregulated with middle ear hypertrophy and biofilm formation in an OM animal model.
- NTHi infection showed less robust GFM upregulation, which was more effectively ameliorated by antibiotic therapy.
- Findings enhance understanding of pathogen-specific effects on mucin expression in OM and may inform clinical treatment strategies.
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