Chronic rhinosinusitis (CRS) is a broadly defined syndrome characterized by prolonged inflammation of the upper airways. Recent culture and sequencing-based studies have identified that the upper airways of CRS-affected individuals harbor bacterial communities marked by decreased bacterial biodiversity, high frequency of Staphylococcus aureus, and notable presence of oral-associated anaerobic bacterial taxa. Further investigation into functions of bacterial communities is warranted to understand their contribution to CRS pathogenesis. The cooperative degradation of host mucin glycoproteins is a community-dependent function that has been investigated for decades, especially in the context of oral and gastrointestinal microbiota. Mucin glycoproteins, the major component of mucus secretions, have been found to act as carbon sources to bacterial consortia that cooperatively degrade them, signaling a potential community-associated trait that can influence chronic infection in the upper airways. To our knowledge, this line of inquiry has not been applied in the context of CRS. This proposal addresses the hypothesis that bacterial consortia capable of cooperative mucin degradation are present in the upper airways of CRS, and through a crossfeeding interaction, can sustain growth and influence virulence gene expression of canonical CRS pathogen S. aureus.
Aim 1 of the proposal will define the keystone microbial community associated with anaerobic degradation of mucins. This will be done through 16S gene sequencing of sinus mucus isolated from CRS patients before and after anaerobic enrichment on mucins as a sole carbon source.
In Aim 2, synthetic and CRS patient-derived mucin-degrading bacterial communities will be used to test the hypothesis that mucin-degradation liberates carbohydrates that can be utilized by S. aureus for growth in an innovative co-culture crossfeeding experimental model.
Aim 3 will test the hypothesis that S. aureus carbon acquisition from mucin degradation influences virulence gene expression through qRT-PCR of several regulatory and virulence associated genes. The proposed research is innovative in both the combination of translational science, bioinformatics, microbial ecology, and classical microbiology techniques. Implication of this community-pathogen crossfeeding interaction in the pathogenesis of CRS will highlight the interconnectedness of the oral and upper airways and encourages collaboration of dentistry and medical professionals in determining treatment for CRS. The results of this research have translational potential to influence antimicrobial therapies for the treatment of CRS.
Oral and craniofacial mucosal surfaces are primary barriers that protect the human body from infection; however, they also asymptomatically harbor microorganisms, leading researchers to investigate what bacterial community interactions influence chronic disease states such as chronic rhinosinusitis (CRS). The proposed research will assess whether mucin degradation contributes to CRS disease etiology through the liberation of carbon sources that can be utilized by pathogens such as Staphylococcus aureus in the nutrient-limited upper respiratory microenvironment. This research will further illuminate how microbial-community-dependent functions contribute to chronic infections, leading to improved design and implementation of new therapeutic strategies for CRS.