Co-infection of the cotton rat ( Sigmodon hispidus) with Staphylococcus aureus and influenza A virus results in synergistic disease

• Published in: Microbial pathogenesis Vol. 43; no. 5; pp. 208 - 216
• Main Authors: Braun, LoRanee E., Sutter, Deena E., Eichelberger, Maryna C., Pletneva, Lioubov, Kokai-Kun, John F., Blanco, Jorge C.G., Prince, Gregory A., Ottolini, Martin G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier India Pvt Ltd 01.11.2007; Elsevier
• Subjects: Animals; Antibodies, Viral - blood; Bacteriology; Biological and medical sciences; Co-infection; Cotton Rat; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Influenza; Influenza A virus; Influenza A Virus, H3N2 Subtype - isolation & purification; Lung - pathology; Lung - virology; Microbiology; Miscellaneous; Orthomyxoviridae Infections - complications; Sigmodon hispidus; Sigmodontinae; Staphylococcal Infections - complications; Staphylococcus aureus; Staphylococcus aureus - isolation & purification; Virology; Co-infection; Influenza; Sigmodon hispidus; Staphylococcus aureus; Cotton Rat; Malvaceae; Mixed infection; Rat; Orthomyxoviridae; Fiber crop; Dicotyledones; Angiospermae; Bacteria; Micrococcales; Micrococcaceae; Rodentia; Infection; Virus; Vertebrata; Influenzavirus A; Mammalia; Influenza A virus; Viral disease; Spermatophyta; Gossypium hirsutum
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2007.03.005

Bacterial super-infection of influenza patients is the primary cause of excess mortality during influenza pandemics, with Staphylococcus aureus ( S. aureus) having the highest fatality rate. The cotton rat ( Sigmodon hispidus) is an excellent model for both influenza and S. aureus pathogenesis, and therefore a potential tool to model co-infection. We compared physiologic and pathologic changes in cotton rats infected with both S. aureus and influenza A/Wuhan/359/95 (H3N2), with animals infected with each pathogen alone. Co-infected cotton rats demonstrated significantly higher mortality, lower temperatures on 2 and 3 days post-inoculation (p.i.), higher levels of bacteremia and pulmonary bacterial load 4 days p.i., and worse pathology 7 days p.i. Early indicators of exacerbated disease coincided with higher pulmonary mRNA levels for IL-1 β, IL-6, IL-10 and IFNy, supporting the idea that these may contribute to disease severity. Our results demonstrate that the cotton rat is a good model of influenza and S. aureus co-infection, with increased mortality and hypothermia as well as prolonged bacterial duration indicative of synergistic disease that may be the result of increased induction of both pro- and anti-inflammatory cytokines.