Document Type

Honors Thesis

Major

Microbiology

Advisor(s)

Robert Wheeler

Committee Members

Benjamin King, Jordan LaBouff

Graduation Year

May 2024

Publication Date

2025

Abstract

Chronic Granulomatous Disease is a human genetic condition characterized by recurrent and severe bacterial and fungal infections due to deficiency in the phagocyte NADPH Oxidase complex NOX2. NOX2 is present in neutrophils and macrophages and produces toxic reactive oxygen species (ROS). In CGD patients the NOX2 complex does not produce ROS due to mutations in one of the components of the complex, most frequently the catalytic subunit gp91. The phagocytes therefore cannot effectively clear infections. NOX1 is a NADPH Oxidase complex that is structurally similar to NOX2 but is primarily expressed in epithelial cells. This means that NOX1 is abundant, and I hypothesized that it may be able to compensate for ROS production in the absence of a functioning NOX2. Pathogens infect many tissues that have both NOX2-expressing immune cells like neutrophils and macrophages and NOX1-expressing epithelial cells meaning NOX1 and NOX2 can be present in similar environments. Whether NOX1 has the potential to compensate for the loss of ROS production caused by the absence of a functioning NOX2 is unknown. In zebrafish model organism, translation of p91 can be inhibited by using a morpholino. Measuring the level of ROS present in NOX2 morphant zebrafish and comparing this to the level found in NOX1 morphants and combination NOX1/NOX2 morphant zebrafish allowed for a comparison of ROS production. Results were varied suggesting that these morphant zebrafish may not currently be a sufficient model for human Chronic Granulomatous Disease and NOX1 is likely not compensating for NOX2.

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