INTELLECTUAL MERIT: Antimicrobial peptides (AMPs) are small proteins found in all living systems. As a part of the innate immune system, they are potent against a broad spectrum of pathogens. Because they are derived from host tissue and have a non-specific mechanism of killing bacteria, AMPs have potential as novel pharmaceutical agents. They are often not as effective against bacteria in vitro as they are in vivo, and sometimes they are toxic to the host tissue. Here it is hypothesized that proper presentation and localization of AMPs onto biocompatible materials will increase their potency against pathogens and limit toxicity toward host cells in vitro. The objectives are to develop nanoscale-patterned surfaces presenting AMPs and to use these systems to quantify the antimicrobial activity and host cell toxicity in response to AMP presentation. A further objective is to modify collagen, currently in wide use as a biocompatible surface coating, with AMPs. The broader objective is to create biomaterials that mimic the in vivo presentation of AMPs to pathogens. The focus is on three AMPs expressed by human ocular surface epithelia. These species will be attached to biocompatible materials with control over density, spacing, and nanoscale patterning to investigate the effect of local AMP concentration and patterning on microbiocidal activity and corneal epithelial cell toxicity. The proposed research capitalizes on a new means of precisely controlling the presentation of AMPs on a size scare not previously available. It will allow quantification of microbiocidal effectiveness and host cell toxicity in response to nanoscale presentation of AMPs.
BROADER IMPACTS: The proposed work is aimed directly at improvements in contact lens fabrication to inhibit eye infections. In addition to these and other novel antimicrobial devices that might emerge from this work, the project will yield new fundamental insights into the mechanism by which AMPs disrupt the bacterial membrane and the role of AMP concentration and cooperativity in determining their activity. The research program will provide interdisciplinary research experience for undergraduate, graduate, and postdoctoral level students. The PI will team with successful University of Houston minority outreach programs to Houston area high schools. He also plans to establish an undergraduate summer internship program with Texas Southern University, a historically minority university located near the University of Houston. Feeder school relationships with Xavier University, Prairie View A&M, and Texas Southern exist to provide research and educational programs accessible to women and minorities.
