The influence of mucins on bacterial communities

Abstract

Mucus is the hydrogel layer that coats all wet epithelia in the body. By supporting commensal microbes and preventing pathogenic invasion, mucus maintains host-microbe homeostasis. Mucin polymers, the primary gel-forming component of mucus, are an important mediator of mucus-microbe interactions. In this thesis, I demonstrate that mucins impact bacterial communities in their physical structure as well as microbe-microbe and microbe-host dynamics. In Chapter 2, 1 study the ability of mucin surface coatings to suppress bacterial surface attachment, the first step in biofilm formation, for Streptococcus pneumoniae and Staphylococcus aureus. Mucin-bound glycans were identified as a critical structural component of mucin coatings that are necessary for bacterial repulsion. In Chapter 3, 1 investigate how mucins impact established Pseudomonas aeruginosa biofilms. The data reveal that mucins cause disassembly and structural rearrangement in P. aeruginosa biofilms in a mucin concentration and flow rate dependent manner. In Appendix A, I show evidence for the involvement of the bacterial flagella in mucinmediated biofilm disruption. Deletion of flagellar capfliD or flagellar stators motABCD results in biofilms that are resistant to mucin-mediated dissociation. In Appendix B, I examine how mucins affect dual-species bacterial communities. I show that mucins promote S. aureus survival during co-culture with P. aeruginosa and also suppress the anti-staphylococcal effects of P. aeruginosa pyocyanin. In Appendix C, I explore the impacts of mucins on P. aeruginosa quorum sensing, an important pathogenic determinant in P. aeruginosa infections. I found that mucins suppress the expression of P. aeruginosa Las and Rhl quorum sensing genes as well as downstream virulence factors. In Appendix D, I assess how mucins modulate P. aeruginosa-epithelium interactions. The data show that mucins hinder the ability of P. aeruginosa to attach to epithelial cells in vitro. Additionally, mucins suppressed P. aeruginosa-associatede pithelial cytotoxicity in a mucin concentration dependent manner. Together, this thesis demonstrates that mucins modulate microbial communities in their behavior and interactions. Understanding how mucus and mucins impact microbes provides insight to host-microbe relationships, as well as for the development of novel bacteria-regulating strategies.