Honey bee (
Apis mellifera
) health has been severely impacted by multiple environmental stressors including parasitic infection, pesticide exposure, and poor nutrition. The decline in bee health is therefore a complex multifactorial problem which requires a holistic investigative approach. Within the exposome paradigm, the combined exposure to the environment, drugs, food, and individuals’ internal biochemistry affects health in positive and negative ways. In the context of the exposome, honey bee hive infection with parasites such as
Nosema ceranae
is also a form of environmental exposure. In this study, we hypothesized that exposure to xenobiotic pesticides and other environmental chemicals increases susceptibility to
N
.
ceranae
infection upon incidental exposure to the parasite. We further queried whether these exposures could be linked to changes in conserved metabolic biological pathways. From 30 hives sampled across 10 sites, a total of 2,352 chemical features were found via gas chromatography-time of flight mass spectrometry (GC-TOF) in extracts of honey bees collected from each hive. Of these, 20 pesticides were identified and annotated, and found to be significantly associated with
N
.
ceranae
infection. We further determined that infected hives were linked to a greater number of xenobiotic exposures, and the relative concentration of the exposures were not linked to the presence of a
N
.
ceranae
infection. In the exposome profiles of the bees, we also found chemicals inherent to known biological metabolic pathways of
Apis mellifera
and identified 9 dysregulated pathways. These findings have led us to posit that for hives exposed to similar chemicals, those that incur multiple, simultaneous xenobiotic stressors have a greater incidence of infection with
N
.
ceranae
. Mechanistically, our results suggests the overwhelming nature of these exposures negatively affects the biological functioning of the bee, and could explain how the decline in bee populations is associated with pesticide exposures.
Synthetic methods for the construction of a novel peptidomimetic structure are reported. The structure incorporates a beta-lactam and an azapeptide in a peptide backbone with the intention of generating rationally designed substrate-based protease inhibitors. The beta-lactam is formed by subjecting serine or threonine-azapeptides to Mitsunobu reaction conditions. Importantly, the azapeptidomimetic beta-lactam structure permits extended binding inhibition and the synthetic methods to create tetrapeptidomimetic structures are described.
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