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THE POLYMICROBIAL NATURE OF OTITIS MEDIA INFECTIONS Michael Dorrington Bowdish Lab MY INTEREST IN THE HUMAN MICROBIOME Infectious disease models involving the upper respiratory tract Streptococcus pneumoniae Relationships among different bacterial species and how these affect colonization and infection as well as disease outcome Development of intranasal vaccine strategies to prevent colonization of common pathogens TOPICS OF DISCUSSION Upper respiratory tract microbial communities and otitis media Laufer et al. “Microbial Communities of the Upper Respiratory Tract and Otitis Media in Children” Feb 2011 The role of quorum signaling in establishing and maintaining infectious biofilms in otitis media infections Armbruster et al. “Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling” July 2010 OTITIS MEDIA Inflammation of the middle ear From tympanic membrane to the cochlea and including the eustachian tube Caused by viral, bacterial, and fungal pathogens S. pneumoniae Haemophilus influenzae Moraxella catarrhalis More common in children <7 years old http://www.dizziness-and-balance.com/images/master-ear.jpg COLONIZATION OF URT INFECTION OF MIDDLE EAR http://www.mhhe.com/biosci/ap/dynamichuman2/content/gifs/0164.gif http://www.atlasaviation.com/medical/Ear.jpg CHILDREN WITH OTITIS MEDIA COLONIZATION VS. INFECTION POLYMICROBIAL INFECTIONS The majority of infectious diseases have more than one causative agent Modulation of host responses Passive antibiotic resistance Quorum signaling Otitis Media Haemophilus influenzae + Moraxella catarrhalis BIOFILMS A complex community of microbes adhering to a surface that comes in regular contact with a fluid Can be made up of numerous species of bacteria, fungi, and/or protazoa Embedded in a self-produced extracellular matrix Normally very resistant to antibiotic treatment QUORUM SIGNALING Bacteria within a biofilm can communicate via signaling molecules Autoinducers N-acyl homoserine lactones (Gram-negative) Oligopeptides (Gram-positive) Signaling molecules can co-ordinate activities between and among different species Signaling often based on threshold population densities BIOFILM FORMATION IN OTITIS MEDIA PASSIVE ANTIBIOTIC RESISTANCE luxS AI-2 THOUGHTS The addition of a single pathogen can induce changes in resident populations of bateria as well as the host This can promote competition or synergism among bacterial species Intranasal probiotics? Upper respiratory tract infections are often polymicrobial in nature Important to gain further understanding of the interactions between commensals and pathogens and how these affect disease outcome