"You stay here, I'm leaving" - S. aureus & S. pneumoniae cocolonisation under influenza A infection
Streptococcus pneumoniae prevents biofilm dispersal of Staphylococcus aureus in dual-species biofilm
- S. aureus and S. pneumoniae shown to coexist in dual species model
- Individually, both species respond to elevated temperature by dispersing
- In co-culture, elevated temperature produced dispersal in only S. pneumoniae
As we all know too well, when our bodies become infected with influenza A virus (IAV), they react in a number of unpleasant ways. One of the characteristics of an influenza infection is fever or elevated temperature, but we are not the only ones who notice, the bacteria in our bodies also feel the heat.
Work done over the past five years has established that two opportunistic pathogens in the upper respiratory tract respond to physiological changes brought about during an IAV infection by dispersing from their biofilms (1,2,3). The bugs in question are Staphylococcus aureus and Streptococcus pneumoniae and the result of this biofilm dispersal is often a serious lung infection.
A collaboration between the State University of New York at Buffalo and Lund University has studied cocolonisation of S. aureus and S. pneumoniae in response to elevated temperatures mimicking fever from an IAV infection. The first exciting finding from the study was that despite previous reports in the literature, both species were capable of coexisting. This is surprising given the strong antagonism between S. aureus and S. pneumoniae.
Secondly, when the mixed species biofilm was subject to elevated temperatures, only the S. pneumoniae was dispersed. The research team led by Anthony Campagnari hypothesise that this is because S. pneumoniae actively modulates the biofilm dispersal of S. aureus.
While it could be argued that the in vitro model is simplistic, the findings were replicated in a murine infection model. The results could help to explain clinical observations of increased rates of cocolonisation in the upper respiratory tract with only S. pneumoniae lung infections significantly increasing.
Streptococcus pneumoniae and Staphylococcus aureus are ubiquitous upper respiratory opportunistic pathogens. Individually, these Gram-positive microbes are two of the most common causative agents of secondary bacterial pneumonia following influenza A virus infection, and they constitute a significant source of morbidity and mortality. Since the introduction of the pneumococcal conjugate vaccine, rates of cocolonization with both of these bacterial species have increased, despite the traditional view that they are antagonistic and mutually exclusive. The interactions between S. pneumoniae and S. aureus in the context of colonization and the transition to invasive disease have not been characterized. In this report, we show that S. pneumoniae and S. aureus form stable dual-species biofilms on epithelial cells in vitro. When these biofilms are exposed to physiological changes associated with viral infection, S. pneumoniae disperses from the biofilm, whereas S. aureus dispersal is inhibited. These findings were supported by results of an in vivo study in which we used a novel mouse cocolonization model. In these experiments, mice cocolonized in the nares with both bacterial species were subsequently infected with influenza A virus. The coinfected mice almost exclusively developed pneumococcal pneumonia. These results indicate that despite our previous report that S. aureus disseminates into the lungs of mice stably colonized with these bacteria following influenza A virus infection, cocolonization with S. pneumoniae in vitro and in vivo inhibits S. aureus dispersal and transition to disease. This study provides novel insight into both the interactions between S. pneumoniae and S. aureus during carriage and the transition from colonization to secondary bacterial pneumonia.
Reddinger RM, Luke-Marshall NR, Sauberan SL, Hakansson AP, Campagnari AA. 2018. Streptococcus pneumoniae modulates Staphylococcus aureus biofilm dispersion and the transition from colonization to invasive disease. mBio 9:e02089-17. https://doi.org/10.1128/mBio.02089-17.
1) Marks LR, Davidson BA, Knight PR, Hakansson AP. 2013. Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. mBio 4:e00438-13. 10.1128/mBio.00438-13.
2) Chao Y, Marks LR, Pettigrew MM, Hakansson AP. 2014. Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease. Front Cell Infect Microbiol 4:194. 10.3389/fcimb.2014.00194.
3) Reddinger RM, Luke-Marshall NR, Hakansson AP, Campagnari AA. 2016. Host physiologic changes induced by influenza A virus lead to Staphylococcus aureus biofilm dispersion and transition from asymptomatic colonization to invasive disease. mBio 7:e01235-16. 10.1128/mBio.01235-16.