STTR Phase I: A Platform of Biomimetic Mucins for Addressing Recurrent Infections

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is the development of effective treatments for recurrent bacterial infections, using biomimetic mucins that restore mucosal tissue homeostasis. Native mucins are a category of molecules that defend mucosal surfaces against infection by selectively domesticating pathogenic microbial populations while supporting commensal populations. When mucosal surfaces are compromised, pathogens can overgrow and cause recurrent infections. Gum disease, irritable bowel syndrome (IBS), and bacterial vaginosis (BV) are all recurrent bacterial infections which affect billions of people worldwide. These seemingly unrelated ailments share the common root cause of compromised mucosal barriers. By developing biomimetic mucins, this project improves upon existing standard-of-care treatments, which address symptoms of disease but do not rectify the underlying mucosal disruption, leading to high rates of recurrence. This project aims to develop scalable and cost-effective biomimetic mucins that exhibit native-like functionalities and can be delivered to mucosal surfaces by incorporation into personal care and dietary supplements. Successful commercialization of this technology will result in a significant reduction in infection and recurrence rates, coupled with a reduction in the associated healthcare expenditures. This Small Business Technology Transfer (STTR) Phase I project will create the first library of biomimetic mucins screened for microbial susceptibility mechanisms—including bacteriostatic, bactericidal, and anti-biofilm activities—against key pathogenic bacteria involved in recurrent infections. To date, biomimetic mucins development has taken an analog discovery route and requires long development timelines that impede commercialization efforts. This project introduces a multiplexed approach for producing and screening a biomimetic mucin library against a wide variety of hallmark pathogenic/commensal microbial strains and epithelial cells for streamlining the discovery route. The goals of this project are to (1) build a library of biomimetic mucins that captures relevant diversity of native mucins (2) screen the library against hallmark microbial strains typical of mucosal surfaces and (3) confirm the cytocompatibility against human epithelial cells. To accomplish these goals multiplexed tools and assays will be pioneered for chemical synthesis and bioactivity evaluation of biomimetic mucins. The output of this undertaking will be a foundational dataset of structure-activity relationships from which top-performing biomimetic mucin variants will be identified for scaled-up manufacturing, in-vivo efficacy testing, and commercialization efforts. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.