Streptococcus pneumoniae Modulates Staphylococcus aureus Biofilm Dispersion and the Transition from Colonization to Invasive Disease

Abstract

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.

Co-carriage of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis among three different age categories of children in Hungary

“…Reddinger et al have performed an interesting experiment in mice: when artificially colonizing the airways of mice with the two bacteria, and then infecting them with influenza virus, only the pneumococcus was able to disperse from the biofilm state and cause pneumonia. This indicated that the pathogenic potential of S. aureus was reduced in the presence of pneumococcus [60]. In the current study, the negative association was obvious.…”

Selective colonization ability of human fecal microbes in different mouse gut environments

“…Second, the composition of the colonizers can also influence colonization ability. For example, Streptococcus pneumoniae and Staphylococcus aureus can form dualspecies biofilms leading to stable co-colonization of the upper respiratory tract, even in a vaccinated host [23]. Finally, intrinsic host factors other than the microbiome can also influence colonization ability of exogenous microbes, for not all microbes can colonize the gut of a germ-free mouse [13].…”

Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia

“…These data imply that influenza infection perturbs the respiratory microbiome, leading to the production of secondary metabolites including immune-modulating molecules. Viruses have also been found to impair bacterial biofilm formation and disrupt existing biofilm ( 141 – 144 ). Influenza has been shown to affect the S. pneumoniae transcriptome in terms of downregulating expression of genes associated with the colonizer state and upregulations of bacteriocins ( 142 ).…”