Developing a pipeline to validate whipworm antimicrobial peptides: a novel opportunity for parasite control

Thomas, Richard (2025) Developing a pipeline to validate whipworm antimicrobial peptides: a novel opportunity for parasite control. Masters by Research thesis (MPhil), Manchester Metropolitan University in collaboration with Queen’s University Belfast..

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Abstract

Trichuris (whipworm) is one of the four soil-transmitted helminths (STH) that causes significant morbidity in humans globally, particularly in children under 15 years of age in tropical/subtropical regions. Currently, the management of STH is reliant on mass drug administration (MDA) campaigns and efforts to improve sanitation infrastructure, however, recent evidence of mounting resistance, especially for T. trichiura, implies the poor efficacy of this strategy. Domestic pigs are also affected by whipworms, as T. suis is an agricultural and economic burden to this industry. Therefore, novel strategies for parasite control are required. Vaccination represents a promising option due to the immunological protection this route can offer. However, previous efforts to develop a Trichuris vaccine have been predominantly unsuccessful. During whipworm infection, the gastrointestinal (GI) microbiome is significantly altered, however, the exact mechanisms by which whipworms alter the microbial composition are still unknown. It is currently theorised that GI helminths possess host defence peptides (HDPs) capable of shaping the surrounding GI microbiota to promote an environment more favourable to chronic infection. This has not yet been explored for Trichuris species, however it may present a new avenue for parasite control, by targeting these HDPs through vaccination and/or novel drugs. This thesis details the development of a pipeline to identify novel Trichuris-derived HDPs. In vitro characterisation (antimicrobial and/or immunomodulatory properties) of 6 HDPs identified by our collaborators at Queen’s University Belfast is also explored in this thesis. Another direction detailed in this thesis is the development of a novel cell-based assay that revealed the immunomodulatory properties of Trichuris-derived HDPs against macrophage-like cells. The resulting data demonstrate that certain Trichuris-HDPs are able to suppress levels of IL-6 and IL-1β production, while others increase IL-10 and either increase or decrease TNF-α production. Hence, this work offers novel insight into how whipworms may be able to alter the surrounding GI microbiota and shape the ongoing immune response to favour their survival.