![]() ![]() To expand available control measures, additional studies to increase available drug options and drug targets are needed. ![]() Additionally, reports of emerging resistance to current treatments have been made 5, 6. Current treatments, while effective at reducing transmission by lowering or eliminating microfilariae circulating in the blood, do not kill the adult worms responsible for the symptoms associated with filariasis 3, 4. More than 7 billion treatments have been delivered in 66 countries to fight lymphatic filariasis as part of the WHO effort to eliminate the disease 1, 3. These 元 larvae then molt and mature as they migrate to the lymphatic system where they complete the lifecycle 1, 2. Within mosquitoes, the microfilariae molt and develop through several stages into the infective third larval stage (元) which can then be transmitted upon a blood meal to other humans. Female worms release millions of microfilariae (immature larvae), which make their way to the bloodstream where they can be ingested by feeding mosquitoes, the insect vector for these parasites. Adult worms residing in the lymphatic system of immunocompetent individuals can survive for an average of 6–8 years. Symptoms in individuals can range from mild to severe including damage to the lymphatic system and kidneys, and eventual clogging of lymphatic vessels with swelling of genitalia and limbs 1, 2. These variations are highlighted in cuticle N-glycoproteins and adult worm restricted N-glycoproteins as examples of proteins at the host parasite interface that are well positioned as potential therapeutic targets or biomarkers.īrugia malayi is one of three human filarial parasites that cause lymphatic filariasis, a debilitating and chronic neglected tropical disease that currently threatens more than 859 million people in 50 countries worldwide 1, 2. Comparing results from adult female worms, adult male worms, and microfilariae, we find variability in N-glycosylation at the protein level as well as at the individual N-glycosite level. Gene ontology and cell localization prediction of the identified N-glycoproteins indicated that they were mostly membrane and extracellular proteins. Our data identified 582 N-linked glycoproteins with 1273 N-glycosites. Fbs1 enrichment of N-glycosylated peptides enhanced the identification of N-glycosites. We then mapped the N-glycosites on proteins from three host stages of the parasite: adult female, adult male and microfilariae. In this study, we applied an enhanced N-glyco FASP protocol using an engineered carbohydrate-binding protein, Fbs1, to enrich N-glycosylated peptides for analysis by LC-MS/MS. Examples of glycosylated Brugia malayi proteins have been previously identified but there has not been a systematic study of the N-linked glycoproteome of this or any other filarial parasite. N-linked glycans are present on surface and secreted filarial proteins that play a role in host parasite interactions. N-linked glycosylation is a critical post translational modification of eukaryotic proteins. ![]()
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