Download Bacterial Otitis Media, the Chinchilla Middle Ear, and Biofilms

EDITORIAL COMMENTARY
Bacterial Otitis Media, the Chinchilla Middle Ear,
and Biofilms
Michael A. Apicella
Department of Microbiology, University of Iowa, Iowa City
(See the article by Reid et al., on pages 786 –94.)
Otitis media in children has a significant
impact on heath care and health-care economics [1]. It is the number one reason
children are seen in physicians’ offices
and the most common reason children
are given antibiotics [2]. The economic
impact was estimated in 1998 to be between $3 billion and $5 billion per year in
the United States. This estimate does not
take into consideration the indirect costs
associated with lost time at work for the
parents of children with chronic and recurrent middle ear infections. In addition, the widespread use of antibiotics for
children treated for otitis media is believed to play an important role in the
marked increase in the extent of antibiotic
resistance as well as the increasing number of resistant strains isolated worldwide. The importance of understanding
the pathogenesis of otitis media, the host
adaptive and innate immune responses,
and the mechanisms for vetting reasonable vaccine candidates is great. Central to
Received 9 June 2008; accepted 11 June 2008; electronically published 30 January 2009.
Potential conflicts of interest: none reported.
Financial support: National Institute of Allergy and Infectious Diseases (grants AI024616, AI30040, and AI045728).
Professor and Head, Department of Microbiology, The
University of Iowa, 51 Newton Road, Iowa City, Iowa 52242
([email protected]).
The Journal of Infectious Diseases 2009; 199:774 –5
© 2009 by the Infectious Diseases Society of America. All
rights reserved.
0022-1899/2009/19906-0002$15.00
DOI: 10.1086/597043
774
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these goals is an animal model that mimics human disease.
The chinchilla inner and middle ear are
uniquely suited to serve as a relevant
model for human otological diseases. The
inner ear has been used by audiologists
and otolaryngologists since 1970 for studies on hearing loss [3]. Giebink et al. demonstrated over 30 years ago that the chinchilla middle ear could be used as a model
for pneumococcal otitis media [4]. Since
that time, Haemophilus influenzae and
Moraxella catarrhalis have been shown to
be capable of inducing bacterial otitis media in the chinchilla [5, 6]. The model
bears many similarities to human disease
and can be induced by intranasal instillation of bacteria after inoculation with a
respiratory virus such as influenza or adenovirus. In 2001, Post showed that both
chinchillas and children with otitis media
had evidence of biofilm formation on
middle ear epithelial surfaces, in their
middle ear secretions, and on tympanostomy tubes [7].
In the article by Reid et al. in this issue
of the Journal [8], the formation of biofilms by pneumococci in a chinchilla middle ear model is clearly demonstrated.
The authors propose that the existence of
the biofilms leads to bacterial persistence.
Using live-dead staining, the authors have
shown that viable bacteria are present in
the entire biofilm and have confirmed
pneumococcal identity by staining with
labeled antibodies for 4 different well-
EDITORIAL COMMENTARY
defined pneumococcal proteins. There
was a considerable amount of neutrophilic infiltration in this biofilm. It appears that neutrophil extracellular traps
(NET) are formed in the biofilm in otitis
media. These NET are made by activated
neutrophils and have been characterized
as bacterial traps [9]. They are formed by
the release of granule proteins and chromatin to form extracellular fibers 15–17
nm in thickness alternating with globular
domains ⬃25 nm in size. Immunochemical analysis has shown that these fibers
contain proteins from the azurophilic
granules such as neutrophil elastase, cathepsin G, and myeloperoxidase [9]. This
observation in the chinchilla is important
in relation to the innate immune mechanisms that operate to clear this infection.
Much additional work is necessary to understand the requirements for pneumococcal biofilm formation, including the
structural features and composition of
the biofilm and the role of quorum sensing in biofilm evolution.
It is clear to all who have worked with
the chinchilla model of otitis media that it
replicates almost all aspects of human disease. To exploit this model fully, a number of important resources are needed.
Most importantly, the genome of this animal should be sequenced. Currently,
studies into the chinchilla innate (or acquired) immune response to otitis media
rely on seeking proteins homologous to
human or murine receptors or effectors
so as to use commercially available reagents.
The implications of biofilm formation
by organisms that colonize and infect humans have undergone considerable discussion in the scientific community. The
studies of Costerton et al. in the 1980s led
the way to the realization that bacterial
biofilms could form on the inert surfaces
of indwelling urinary and vascular catheters [10, 11]. This view was at the time
very controversial, but it is taken for
granted today. The studies of Pearson et
al. demonstrated that quorum sensing
was involved in biofilm formation [12,
13] by the human opportunistic pathogen
Pseudomonas aeruginosa. Since that time,
the importance of biofilm formation as a
component of human disease and colonization has evolved to include an increasing list of microbes and now includes the
concept that biofilms can form on biological surfaces, such as the airway of patients
with cystic fibrosis or the middle ear of a
young child. The concept that organisms
in biofilms are significantly more resistant
to antimicrobial therapy than the same
organisms under standard culture conditions has implications for the management of infections, emerging antimicro-
bial resistance, and the role of biofilm
formation in disease outcome and recurrence. The chinchilla model of otitis can
serve as an excellent tool to study the contribution biofilms may make to the evolution of antimicrobial resistance in pneumococcal and nontypeable H. influenzae
infections.
Many factors influence the frequency
and severity of otitis media in children including genetics, age, anatomy, and environment. The goal of limiting or eliminating this childhood infection by
vaccination or enhancement of innate
immune responses should be a priority
for future biomedical research funding.
5.
6.
7.
8.
9.
10.
References
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