TY - JOUR T1 - Synergism and antagonism of bacterial-viral co-infection in the upper respiratory tract JF - bioRxiv DO - 10.1101/2020.11.11.378794 SP - 2020.11.11.378794 AU - Sam Manna AU - Julie McAuley AU - Jonathan Jacobson AU - Cattram D. Nguyen AU - Md Ashik Ullah AU - Victoria Williamson AU - E. Kim Mulholland AU - Odilia Wijburg AU - Simon Phipps AU - Catherine Satzke Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/11/2020.11.11.378794.abstract N2 - Streptococcus pneumoniae (the pneumococcus) is a leading cause of pneumonia in children under five years old. Co-infection by pneumococci and respiratory viruses enhances disease severity. Little is known about pneumococcal co-infections with Respiratory Syncytial Virus (RSV). Here, we developed a novel infant mouse model of co-infection using Pneumonia Virus of Mice (PVM), a murine analogue of RSV, to examine the dynamics of co-infection in the upper respiratory tract, an anatomical niche that is essential for host-to-host transmission and progression to disease. Coinfection increased damage to the nasal tissue and increased production of the chemokine CCL3. Pneumococcal nasopharyngeal density and shedding in nasal secretions were increased by co-infection. In contrast, co-infection reduced PVM loads in the nasopharynx, an effect that was independent of pneumococcal strain and the order of infection. We showed this ‘antagonistic’ effect was abrogated using a pneumococcal mutant deficient in capsule production and incapable of nasopharyngeal carriage. The pneumococcal-mediated reduction in PVM loads was caused by accelerated viral clearance from the nasopharynx. Although these synergistic and antagonistic effects occurred with both wild-type pneumococcal strains used in this study, the magnitude of the effects was strain dependent. Lastly, we showed that pneumococci can also antagonize influenza virus. Taken together, our study has uncovered multiple novel facets of bacterial-viral co-infection. Our findings have important public health implications, including for bacterial and viral vaccination strategies in young children.Competing Interest StatementSM, OW and CS have each received a Robert Austrian Research Award in Pneumococcal Vaccinology funded by Pfizer unrelated to this study. CS is an investigator on an unrelated study funded by Pfizer. ER -