Frenemies: Microbial Interactions in Respiratory Diseases

No microbe exists in isolation. When we become infected with a respiratory pathogen, like influenza, our bodies harbor not just the current influenza strain making the news; they share space with other drug-resistant variants and bacterial species. Together, these “bugs” set off a complex set of interactions that impact viral evolutionary dynamics and skew clinical outcome and can lead, for example, to pneumonia. They also keep bad company with other infections that likewise can affect the host’s immune response, such as HIV, which can modulate the interactions among the members of the respiratory microbiome. For all the damage they do, however, these interactions in the human respiratory tract are essentially uncharted territory in the scientific realm. Our work has begun to make inroads into this territory by characterizing in animal models and clinical samples the microbial ecology in the upper and lower respiratory tract in the context of two infections—influenza and HIV—and lung diseases like chronic obstructive pulmonary disease (COPD). What we have found so far is a restructuring of the microbial environment during disease, including interactions among and between bacteria and fungi. The latter, which are often present at a much lower abundance, nevertheless play a leading role in the organization and stability of the microbial community. I’ll show how this works and how we plan to probe the microbial environment and networks of interaction so that we can develop predictive modeling of disease severity, potentially leading to novel therapies.