In Vivo Localization of Staphylococcus aureus in Nasal Tissues of Healthy and Influenza A Virus-Infected Ferrets

Abstract

An in vivo ferret model was used to study the association of Staphylococcus aureus with specific tissues of the nasal cavity in both control and influenza A virus-infected animals. Ferrets were inoculated intranasally with various doses of influenza A3/Hong Kong/1/68 virus. On Days 2, 5, 9 and 14, four or five virus-inoculated and two uninoculated controls were challenged intranasally with a 1-ml volume of radiolabeled S. aureus (3 mg dry wt), a clinical isolate of low passage history. Ferrets were allowed to clear the staphylococci in vivo for 60 to 90 min before sacrifice. The animals were anesthetized, exsanguinated, and decapitated, and the lower jaw was removed. The nasal fossae were exposed by dissection and turbinates from the left nasal fossa were used for virus isolation. The median septum and tissues from the right nasal fossa, which included vestibule and anterior and posterior turbinates, were harvested and processed for radioassay. The percentage of recoverable staphylococci from virus-infected ferrets (Days 2 and 5) was ≥ 10-fold higher compared with controls and animals infected with suboptimal doses of virus; ≥ 76% of the recoverable staphylococci, whether from controls or virus-infected animals, was associated with the anterior turbinates. Histologic examination of the anterior turbinates from virus-infected ferrets, particularly on Days 2 and 5 postexposure to virus, showed that the staphylococci were adhering to desquamating respiratory epithelial cells. In contrast, the anterior turbinates from control ferrets uninoculated with virus and posterior turbinates from both control and virus-infected animals showed no evidence of bacteria adhering to host cells; instead, the staphylococci were found in association with the mucus gel layer of respiratory mucosa. Examination of vestibular tissue showed staphylococci in association with cells of the stratum granulosum in both virus-infected and control animals. Results of this study suggest that the early events of S. aureus interaction with different sites of ferret nasal tissues are effected by different mechanisms, and that the interaction is significantly enhanced by virus-infection.