T HE P OLYMICROBIAL N ATURE OF O TITIS M EDIA I NFECTIONS Michael Dorrington Bowdish Lab

M Y I NTEREST IN THE H UMAN M ICROBIOME 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

T OPICS OF D ISCUSSION 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

O TITIS M EDIA 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

C OLONIZATION OF URT  I NFECTION OF M IDDLE E AR

C HILDREN WITH O TITIS M EDIA

C OLONIZATION VS. I NFECTION

P OLYMICROBIAL I NFECTIONS 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

B IOFILMS 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

Q UORUM S IGNALING 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

B IOFILM FORMATION IN O TITIS M EDIA

P ASSIVE ANTIBIOTIC RESISTANCE

luxS  AI-2

T HOUGHTS 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