Host-Microbe Interactions in Mucus – From Mechanism to Application
Mucus is an important but understudied barrier that lines an enormous surface area in our body (2000 square feet in the intestine alone). Our goal is to understand the role of mucus in health and disease. Specifically, we aim to understand how mucus barriers exclude, or allow, passage of different molecules and pathogens, and the mechanisms pathogens have evolved to penetrate mucus barriers.
Largely invisible to the eye is the clear and slimy mucus gel that lines all wet surfaces in the body, including oral cavity, respiratory, gastrointestinal, and urogenital tracts. Shown here is an image at high magnification of mucin polymers, long and thread like polymers that build the mucus gel. Mucin polymers coat all the wet surfaces in the human body, providing a selective barrier that allows nutrients and information in while keeping pathogens out.
Our laboratory works in three areas of mucus biology
Mucus is home to trillions of microbes that form our microbiota and regulates their interactions with the host. Our goal is to identify the mechanisms mucus has evolved to control problematic pathogens, preventing them from causing harm. Our work has begun to reveal that mucus, and specifically its gel-forming mucin polymers, are key host players in the regulation of microbial virulence that can suppress a range of virulence traits in microbes, such as quorum sensing, the formation of biofilms, and horizontal gene transfer. Our mission is to guide new strategies to target infections, neutralize microbial virulence, and the design of anti-biofilm coatings for implants.
The physicochemical properties of mucus barriers are closely related to health and disease, and the pathological onset of mucus barrier dysfunction can lead to a number of devastating pulmonary, gastrointestinal and urogenital conditions. Our goal is to establish structure-function relationships between mucus’ physicochemical properties and epithelial health to better understand and predict disease progression on mucosal epithelia, and direct the design of intervention strategies.
Any device or drug in the gut, the reproductive tract or the eye is immersed in mucus, and its performance will be largely defined by this interaction. Our experimental and theoretical framework will understand the basic principles that govern selective transport through the mucus barrier. It will also provide tools to predict the trafficking and fate of pathogens and drug delivery vehicles in the mucus barrier, which has significant implications for the prediction and treatment of infectious diseases.
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Wheeler et al. show that soluble glycans isolated from mucin polymers downregulate key virulence pathways involved in toxin secretion, bacterial communication, and biofilm formation in the opportunistic pathogen, Pseudomonas aeruginosa.
Wang and Wheeler et al. identify the first bacterial receptor for mucin glycans as RetS, a well-characterized sensor kinase. By activating RetS through its carbohydrate-binding Dismed2 domain, mucin glycans directly inhibit virulence-associated traits including the type VI secretion system (H1-T6SS), which enables P. aeruginosa to kill neighboring microbes.
Smith-Dupont et al. highlight that cervical mucus from pregnant women at risk for preterm birth is more permeable
than that from women with healthy pregnancies.