Coinfection of Streptococcus pneumoniae reduces airborne transmission of influenza virus

Mueller Brown, K.; Le Sage, V.; French, A. J.; Jones, J. E.; Padovani, G. H.; Avery, A. J.; Myerburg, M. M.; Schultz-Cherry, S.; Rosch, J. W.; Hiller, N. L.; Lakdawala, S. S.

doi:10.1101/2020.11.10.376442

bioRxiv · 10.1101/2020.11.10.376442

Coinfection of Streptococcus pneumoniae reduces airborne transmission of influenza virus

Mueller Brown, K.·Le Sage, V.·French, A. J.·Jones, J. E.·Padovani, G. H.·Avery, A. J.·Myerburg, M. M.·Schultz-Cherry, S.·Rosch, J. W.·Hiller, N. L.·Lakdawala, S. S.

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Abstract

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.

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Mueller Brown, K., Le Sage, V., French, A. J., Jones, J. E., Padovani, G. H., Avery, A. J., Myerburg, M. M., Schultz-Cherry, S., Rosch, J. W., Hiller, N. L., Lakdawala, S. S.. 2020-11-10. Coinfection of Streptococcus pneumoniae reduces airborne transmission of influenza virus. https://doi.org/10.1101/2020.11.10.376442

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