Browsing by Subject "Mucin"

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    Bacterial communities associated with chronic rhinosinusitis and the impact of mucin degradation on Staphylococcus aureus physiology
    (2020-08) Lucas, Sarah
    Chronic rhinosinusitis (CRS) is a heterogeneous disease of the paranasal sinuses. Anatomic variation, genetic mutation, viral infection, and allergic response, are all considered to play etiological roles in CRS. Contributors to pathogenesis include immune dysfunction, impaired mucociliary clearance, increased mucus production and stasis, and bacterial virulence mechanisms, however their importance and order of occurrence is not well understood. Microbiological surveys have implicated Staphylococcus aureus as one of the most frequent bacteria in the CRS sinuses. Paradoxically, S. aureus asymptomatically colonizes the nasal passages of ~50% of healthy adults. This work aimed to further describe the diversity of bacterial communities in the paranasal sinuses of patients with CRS using genomic and bioinformatic methods, and reveal new insights into the balance between S. aureus commensalism and pathogenesis. CRS is particularly prevalent in people with the genetic disorder cystic fibrosis (CF). Bacterial infection of the upper airways is thought to be a focus for pulmonary infection, which accounts for the majority of morbidity and mortality in this population. Using 16S rRNA gene sequencing, we described highly similar bacterial communities between sinus mucus and lung sputum in CF patients. CF patients exhibited high interindividual variation, and several instances where a canonical CF pathogen (e.g. S. aureus, Pseudomonas aeruginosa) was seen in the sinus mucus, but not sputum, suggesting this is a location of initial pathogen colonization and adaptation. Further investigation of the bacterial communities in sinus mucus revealed that diversity of the bacterial community was significantly greater in communities with S. aureus as the dominant organism. In contrast, Pseudomonas dominated communities were less diverse, and associated with both increased patient age, and decreased lung function, though not significantly. These results contribute to a growing body of research suggesting a temporal progression of bacterial diversity in the CF airways towards a community characterized by P. aeruginosa dominance. We further hypothesized that the presence of other bacterial taxa could have differential effects on S. aureus physiology in the non-CF CRS. Using 16S rRNA gene sequencing, the bacterial communities were characterized in CRS and non-CRS patient sinus mucus accessed through endoscopic sinus surgery. Compared to the bacterial communities observed in non-CRS mucus, CRS was characterized by an increased proportional abundance of facultative and obligate anaerobic bacterial genera including Streptococcus, Prevotella, and Fusobacterium, and a decrease in Actinobacteria compared. Guided by taxonomy, we computationally predicted the metagenomic content of CRS-associated communities, which suggested an increased functional capacity for the degradation of mucin-glycoproteins - a highly abundant constituent of mucus responsible for its many biological and physical characteristics. Using anaerobic enrichment of CRS sinus mucus bacterial communities on mucins in a minimal medium, we demonstrated a mucin-degradation phenotype, and further described the bacterial communities to include anaerobic genera such as Streptococcus, Prevotella, Veillonella, and Fusobacterium. This work shows that mucins are not efficiently used as a growth substrate by S. aureus, however, mucin degradation and fermentation by CRS-derived bacterial consortia produced metabolites that could augment S. aureus growth. Furthermore, transcriptomic analysis suggests mucin degradation and fermentation products affect S. aureus metabolic state and virulence potential. This work presents high-resolution molecular characterization of the bacterial communities associated with CRS, demonstrates mucin-degradation as a bacterial phenotype carried out by these communities, and suggests a role for mucin-degradation in supporting the growth and virulence of S. aureus.