Bacterial superinfections following influenza A virus (IAV) are predominant causes of morbidity in humans. The recent emergence of methicillin-resistant Staphylococcus aureus (MRSA) and highly virulent IAV strains has reduced treatment options. Development of an appropriate animal model to study secondary S. aureus infections may provide important information regarding disease pathogenesis. Pigs are natural hosts to both IAV and S. aureus and have respiratory physiology and immune response comparable to humans. To establish a time course of susceptibility to S. aureus after IAV infection, nursery pigs infected intranasally with IAV were challenged with MRSA at different time points. Lung pathology scores and MRSA CFU were evaluated in dual-infected animals after IAV infection. Flow cytometric analysis of bronchoalveolar lavage fluid indicated differences between treatments. These results demonstrate the appropriateness of an intranasal challenge model in nursery pigs for studying the pathogenesis of IAV and S. aureus coinfection and provide insights into the timeframe for susceptibility of IAV-infected pigs to secondary S. aureus infection. 1. Introduction Influenza A virus (IAV) infections in humans are generally mild and not often fatal; however, morbidity and mortality significantly increase with bacterial superinfections [1, 2]. Staphylococcus aureus commonly causes pneumonia in influenza patients, and methicillin-resistant strains currently account for 20–40% of all community-acquired pneumonia (CAP) [3]. The increasing prevalence of antibiotic-resistant bacteria, emergence of highly virulent IAV strains, and recent pandemics necessitate development of an appropriate animal model of polymicrobial infections to understand the pathogenesis and to identify intervention strategies. The majority of animal studies use adapted strains of IAV, which induce fatal respiratory disease atypical of human infection [4, 5]. Development of appropriate animal models to study the mechanisms of pathogenesis may provide important information for disease prevention, diagnosis, and treatment. Mice have traditionally been used to study IAV and bacterial coinfection. Although mice coinfected with Streptococcus pneumoniae and IAV suffer from more severe bronchopneumonia than mice with a single infection [6], disease synergy is not evident in the mouse model of S. aureus and influenza [7]. Furthermore, the IAV strains used in mouse coinfection studies are adapted to replicate effectively within the mouse, limiting the likeness of this model to human infection.
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