The otic microbiome and its role in middle ear decompression and barotrauma prevention
Abstract
The proposed research seeks to gain fundamental understanding of the otic microbiome and itscontribution to middle ear decompressio"n and barotrauma prevention. The middle ear comprisesthe tympanic cavity and its extension into the nasopharynx, the Eustachian Tub""e (ET), whichprovides a passage for nasopharyngeal bacteria. Bacterial colonization of the otic mucosainvolves specific recognitio""n of mucosal antigens (such as mucins) by the bacteria and celllocomotion by swarming, a flagellum-driven motility that relies on s"urfactant lubrication topropel cells through the viscous mucoid fluid that coats the ET walls. The discovery thatbacterial microcolonies grow within the mucosal epithelium of the tympanic cavity suggests thatnasopharyngeal swarmers may also colonize the seclude"d middle ear microenvironment. Aerialcell dispersion may also be significant. Indeed, the middle portion of the ET is collapsed but""opens rhythmically with swallowing (and yawning) to aerate the middle ear, equalize pressureacross the tympanic membrane, and drai"n excess mucus into the nasopharynx. Surfactants in themucus reduce its surface tension and facilitate ET patency. We hypothesize that some of thesame surfactants produced by bacteria for locomotion will have the activity needed to modulateET mechanics. Further"more, protease production may be significant, as reduces the mucusviscosity and facilitates colonization of the mucosa. By influenc""ing the viscoelastic properties ofthe mucus, bacterial proteases modulate ET patency and fluid drainage. To test these hypotheses,""we propose three tasks, which cover the base project (task 1) and two options (tasks 2 and 3):Base: To isolate surfactant-producing" bacteria from the ET of healthy individuals (task 1).Option 1: To identify strains that express surfactants with highest surface a"ctivity (task 2).Option 2: To develop synthetic otic communities for surfactant-controlled, middle earventilation (task 3).The ba""se project (task 1, $295,954) is planned for 15 months and will begin with the collectionof ET secretions from divers and non-diver""s, which will provide the samples needed to sequencethe otic metagenome and to isolate surfactant-producing bacteria under conditio"ns ofpressurization and aeration relevant to the middle ear and ET microenvironment. Successfulcompletion of this task will allow" us to pursue the next tasks. Option 1 (task 2, 12 months,$242,025) will investigate the properties of the bacterial surfactants, t""heir molecular basis, andgenetic manipulation. Option 2 (task 3, 9 months, $187,013) will harness this information todevelop synth"etic otic communities for functional studies (transcriptomics) that will reveal howthe community responds and acclimates to the mid"dle ear and ET microenvironment.PI Reguera will lead the efforts of a team comprised of three additional members: co-PI Kashefi,a"" postdoc, and an undergraduate student helper. Together, we will gain fundamentalunderstanding of the otic community structure and" its contribution(s) to host functions and otichomeostasis. Findings from this work are relevant to ONR because increasing our understandingof the otic microbiome can potentially lead to the development of bacterial replacement therapiesthat promote middle ear" decompression and prevent barotrauma in ~Navy and Marine Corpspersonnel during training, routine and special operations, and in ti"me of war.~.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 01, 2017
- Source ID
- N000141712678
Entities
People
- Gemma Reguera
Organizations
- Michigan State University
- Office of Naval Research
- United States Navy