CommensalNose

Nasal commensal bacteria interface with nasal mucosa to maintain homeostasis. For this commensals shape host transcriptional responses by activating chromatin-remodeling enzymes to promote or restrict the accessibility of DNA to transcription machinery across gene loci. However, the commensal-host balance must remain responsive to trigger cellular immunity to colonizing pathogens. In fact, pathogen disruption of nasal/commensal regulatory capacity precedes pathogenic outgrowth and disease– this is the “microbial barrier to disease”. Corynebacterium accolens (Ca) is a key commensal of healthy human nasal epithelium, and when displaced increases risk for respiratory disease. Yet our knowledge of mechanisms shaping Ca–nasal epithelial crosstalk remain understudied, with even less mechanistic insight into how pathogens alter this. Streptococcus pneumoniae (Spn) is an opportunistic pathogen and an obligate colonizer of the human nasal passage/upper respiratory tract. Colonization by different Spn serotypes results in either commensal-like retention and nasal carriage, or in invasive bacterial progression past the nasal passage, which increases the potential for disease. Interestingly, new studies show Ca kills invasive favoring Spn by generating anti-pneumococcal fatty acids from host components. Thus, a Spn-Ca paradox arises; Commensal-like Spn would need to synergize or minimally disturb Ca–host interaction to maintain homeostasis in asymptomatic carriage, while an invasive serotype would need to disrupt this for progression to symptomatic disease. We hypothesize Ca–nasal cell crosstalk drives commensal phenotypes and selectively protects against Spn colonization in a serotype dependent manner. Our objective is to understand 1) How Ca shapes the host chromatin landscape and the resulting nasal cell immunity, 2) how Ca protects against Spn colonization and 3) how Spn colonization disrupts Ca-host homeostasis on a chromatin level.