What’s on the menu matters: diet-dependent remodelling of the larval peritrophic matrix glycoproteome in the Australian sheep blowfly

Flystrike, the infestation of the skin by larvae of predominately Australian Sheep Blowfly on Sheep, costs the Australian sheep industry more than $320 million annually. The peritrophic matrix (PM) is a chitin–protein barrier lining the insect midgut that is essential for digestion, protection, and host–parasite interactions. In Lucilia cuprina larvae, the PM is also a proven vaccine target, yet how diet influences its molecular composition remains unclear. Here, we used integrated proteomics, glycoproteomics, glycomics, and transcriptomics to examine diet-dependent PM structure. Larval diet strongly altered PM protein composition, particularly the abundance of peritrophins, while PM glycosylation remained highly conserved and dominated by oligomannose-type N-glycans. Transcriptomic data indicated that simplified diets induce ER-associated responses consistent with post-transcriptional regulation of PM assembly. Importantly, these compositional changes directly correlated with reduced vaccine efficacy. Together, our findings demonstrate that larval diet governs PM structure and immunogenic potential, with direct implications for vaccine antigen selection and PM production.