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Mueller Brown, K.

Publications and source records attributed to Mueller Brown, K..

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Detection of Influenza virus and Streptococcus pneumoniae in air sampled from co-infected ferrets and analysis of their influence on pathogen stability

Secondary infection with Streptococcus pneumoniae has contributed significantly to morbidity and mortality during multiple influenza virus pandemics and remains a common threat today. During a concurrent infection, both pathogens can influence the transmission of each other, but the mechanisms behind this are unclear. In this study, condensation air sampling and cyclone bioaerosol sampling were performed using ferrets first infected with the 2009 H1N1 pandemic influenza virus (H1N1pdm09) and secondarily infected with S. pneumoniae strain D39 (Spn). We detected viable pathogens and microbial nucleic acid in expelled aerosols from co-infected ferrets, suggesting that these microbes could be present in the same respiratory expulsions. To assess whether microbial communities impact pathogen stability within an expelled droplet, we performed experiments measuring viral and bacterial persistence in 1 L droplets. We observed that H1N1pdm09 stability was unchanged in the presence of Spn. Further, Spn stability was moderately increased in the presence of H1N1pdm09, although the degree of stabilization differed between airways surface liquid collected from individual patient cultures. These findings are the first to collect both pathogens from the air and in doing so, they provide insight into the interplay between these pathogens and their hosts. ImportanceThe impact of microbial communities on transmission fitness and environmental persistence is under-studied. Environmental stability of microbes is crucial to identifying transmission risks and mitigation strategies, such as removal of contaminated aerosols and decontamination of surfaces. Co-infection with S. pneumoniae is very common during influenza virus infection, but little work has been done to understand whether S. pneumoniae alters stability of influenza virus, or vice versa, in a relevant system. Here, we demonstrate that influenza virus and S. pneumoniae are expelled by co-infected hosts. Our stability assays did not reveal any impact of S. pneumoniae on influenza virus stability, and a trend towards increased stability of S. pneumoniae in the presence of influenza viruses. Future work characterizing environmental persistence of viruses and bacteria should include microbially-complex solutions to better mimic physiologically relevant conditions.

microbiology↗

Coinfection of Streptococcus pneumoniae reduces airborne transmission of influenza virus

Secondary bacterial infection, especially with Streptococcus pneumoniae (Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naive recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one. SignificanceAirborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection with Streptococcus pneumoniae reduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.

microbiology↗