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infection (4,5,6,7) , and a significant correlation has been demonstrated between
the colonizing strains of S. aureus and the strains of S. aureus in infected
individuals. As the incidence of community-associated methicillin-resistant S.
aureus infections continues to rise (8) , there appears to be a parallel increase in
nasal colonization with methicillin-resistant S. aureus (MRSA) (1) . Strategies
to reduce S. aureus nasal colonization and thus reduce infection rates have
met with mixed success (9,10,11,12,13) , but this type of prophylaxis may still
prove to be an important intervention that can effectively reduce overall S.
aureus infection rates. This chapter details an animal model for studying S.
aureus nasal colonization, which allows for both investigation of staphylococcal
factors that play a role in nasal colonization as well as allowing for screening
of potential therapies to eradicate S. aureus nasal colonization.
The cotton rat ( Sigmodon hispidus ) is a well-established model for a number
of human pathogens, especially viral respiratory pathogens (14,15) . The model
detailed in this chapter is an adaptation of a model of S. aureus nasal
colonization originally described in mice (16) but now adapted to cotton rats.
The cotton rat's nasal histology is comparable to that of humans (17) and pre-
treatment of cotton rats with antibiotics like streptomycin is not required as it
is in mice (16) to establish nasal colonization by S. aureus . We have success-
fully used the cotton rat S. aureus nasal colonization model to demonstrate the
efficacy of lysostaphin as a therapy for S. aureus nasal colonization (18) as
well as to study the roles of wall teichoic acid (19) and IsdA and IsdH (20) of
S. aureus in nasal colonization.
This chapter will describe in detail the materials and methods necessary for
studying this cotton rat model of S. aureus nasal colonization. These steps
include (1) instillation of the S. aureus to establish nasal colonization, (2)
treatment of the nares with various therapeutic agents, and (3) recovery and
enumeration of colonizing S. aureus .
2. Materials
2.1. Instillation
1. Cotton rats ( Sigmodon hispidus ) (14) may be purchased from Harlan (Hsd:Cotton
Rat, Indianapolis, IN). There are also several breeding colonies that may be able
to provide animals, including colonies at Virion Systems (Gaithersburg, MD)
and Baylor College of Medicine (Houston, TX). Cotton rats should be 6 weeks
old or older for use in this model ( see Note 1 ).
2. Frozen stocks of S. aureus ( see Note 2 ).
3. Tryptic soy broth (TSB): As per the manufacturer's instructions, 30 g/L in
ddH 2 O.
 
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