Bacterial infections associated with chronic airway disease (cystic fibrosis, COPD, sinusitis) are composed of complex polymicrobial communities that incite persistent inflammation and airway damage. Despite the recent surge in microbiome studies characterizing the composition of airway microbiota, a lack of effective therapeutics remains, due in part to our limited understanding of how bacterial species interact with one another in vivo, how they adapt to the airway microenvironment, and their co-evolution over time. The overarching research focus of the Hunter lab is to combine genomics, imaging, analytical biochemistry, and bacterial genetics, to better understand the in vivo host chemical environment, how it shapes polymicrobial interactions within, and to manipulate the environmental-microbe dynamic as a novel therapeutic strategy.

Our entry in this research area began with our observation that canonical pathogens of cystic fibrosis (CF) airway (e.g. Pseudomonas aeruginosa, Staphylococcus aureus) are surprisingly inefficient at metabolizing mucin glycoproteins that comprise the major macromolecular constituent (and bioavailable carbon source) of airway mucus. Given that P. aeruginosa and S. aureus can reach densities of >109 cells per gram of mucus, our data suggested that mucin-derived nutrient acquisition may be supported by other processes. Informed by our microbiome sequencing data, we hypothesized that anaerobic “commensal” microbes, which are adept at degrading and fermenting mucins in the oral cavity (i.e. saliva) and also found in abundance in the infected lower airways, could stimulate pathogen growth through mucolytic activity. Indeed, we found that oral-associated anaerobic genera such as Prevotella, Fusobacterium, Streptococcus, and Veillonella spp. generate short-chain fatty acids (propionate, butyrate) and amino acids via mucin degradation that stimulate pathogen growth and virulence. This study, which defined a new role for “commensal” bacteria in CF airway disease opened up an exciting new area of microbial ecology that we and others continue to explore in the context of CF, chronic sinusitis, and other sites of infection.