Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2021

Synergistic and antagonistic interactions between Streptococcus pneumoniae and respiratory viruses in an infant mouse model (#39)

Sam Manna 1 2 3 , Julie McAuley 3 , Jonathan Jacobson 1 , Cattram Nguyen 1 , Ashik Ullah 4 , Victoria Williamson 1 , E. Kim Mulholland 1 2 , Odilia Wijburg 3 , Simon Phipps 4 , Catherine Satzke 1 2 3
  1. Murdoch Childrens Research Institute, Parkville, VIC, Australia
  2. Department of Paediatrics,, The University of Melbourne, Parkville, VIC, Australia
  3. Department of Microbiology & Immunology at the Peter Doherty Institute for Infection & Immunity,, The University of Melbourne, Parkville, VIC, Australia
  4. QIMR Berghofer Medical Research Institute, Brisbane, QLD

Streptococcus pneumoniae (the pneumococcus) is a leading cause of pneumonia in children and co-infection with respiratory viruses enhances disease severity. Although pneumococcal-influenza co-infections have been well investigated, less is known about pneumococcal co-infections with Respiratory Syncytial Virus (RSV), a major cause of bronchiolitis in infants.

In this study, we developed an infant mouse co-infection model using Pneumonia Virus of Mice (PVM, a murine analogue of RSV). Our study focuses on bacterial-viral interactions in the upper respiratory tract (the nasopharynx), which serves as a pre-cursor to disease and a reservoir for host-to-host transmission. We demonstrated that PVM infection increased pneumococcal nasopharyngeal density and shedding in nasal secretions, but not acquisition of pneumococci by naive hosts. These data suggest the virus enhances the early stages of pneumococcal transmission. Co-infection increased damage to the nasal tissue and production of the chemokine CCL3.

Unexpectedly, mice colonised with pneumococci had reduced viral loads 11 days post-PVM infection. This ‘antagonistic’ effect was not dependent on pneumococcal strain and occurred regardless of the order of infection. We showed that the antagonism is absent when using a pneumococcal mutant deficient in capsule production. Examination of viral loads over time revealed that the antagonism was due to accelerated clearance of the virus from the nasopharynx. Lastly, we showed that pneumococci can also antagonize influenza by restricting viral replication. While the consensus in the field is that pneumococcal-viral co-infection is synergistic, our study has uncovered novel aspects of the relationship that are antagonistic. Future studies will focus on uncovering the mechanism of this antagonism and the public health implications of our findings for bacterial and viral vaccination strategies in young children.