Modulates Biofilm Dispersion and the Transition from Colonization to Invasive Disease.

and 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 and in the context of colonization and the transition to invasive disease have not been characterized. In this report, we show that and form stable dual-species biofilms on epithelial cells When these biofilms are exposed to physiological changes associated with viral infection, disperses from the biofilm, whereas dispersal is inhibited. These findings were supported by results of an 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 disseminates into the lungs of mice stably colonized with these bacteria following influenza A virus infection, cocolonization with and inhibits dispersal and transition to disease. This study provides novel insight into both the interactions between and during carriage and the transition from colonization to secondary bacterial pneumonia. In this study, we demonstrate that can modulate the pathogenic potential of in a model of secondary bacterial pneumonia. We report that host physiological signals related to viral infection cease to elicit a dispersal response from while in a dual-species setting with , in direct contrast to results of previous studies with each species individually. This study underscores the importance of studying polymicrobial communities and their implications in disease states.