Back to Search
Start Over
A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development
- Source :
- PLoS Pathogens, PLoS Pathogens, Vol 14, Iss 3, p e1006931 (2018), Bouchery, T, Filbey, K, Shepherd, A, Chandler, J, Patel, D, Schmidt, A, Camberis, M, Peignier, A, Smith, AAT, Johnston, K, Painter, G, Pearson, M, Giacomin, P & LeGros, G 2018, ' A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development. ', PLoS Pathogens . https://doi.org/10.1371/journal.ppat.1006931
- Publication Year :
- 2018
- Publisher :
- Public Library of Science, 2018.
-
Abstract
- As part of on-going efforts to control hookworm infection, the “human hookworm vaccine initiative” has recognised blood feeding as a feasible therapeutic target for inducing immunity against hookworm infection. To this end, molecular approaches have been used to identify candidate targets, such as Necator americanus (Na) haemoglobinase aspartic protease-1 (APR-1), with immunogenicity profiled in canine and hamster models. We sought to accelerate the immune analysis of these identified therapeutic targets by developing an appropriate mouse model. Here we demonstrate that Nippostrongylus brasiliensis (Nb), a phylogenetically distant strongylid nematode of rodents, begins blood feeding early in its development and that immunisation with Na-APR-1 can block its growth and completion of its life cycle. Furthermore, we identify a new haem detoxification pathway in Nb required for blood feeding that can be blocked by drugs of the quinolone family, reducing both infection burden and the associated anaemia in rodents. Collectively, our findings show that haem metabolism has potential as a checkpoint for interrupting hookworm development in early stages of the hookworm life cycle and that the Nippostrongylus brasiliensis rodent model is relevant for identifying novel therapeutic targets against human hookworm.<br />Author summary Hookworm infections (Necator americanus or Ancylostoma duodenale) represent a major neglected tropical disease affecting approximately 450 million people worldwide and causing morbidity due to their need to feed on host blood resulting in severe anemia. New chemotherapy and vaccines are needed to combat hookworm infections. Using a rodent parasite model, we describe a new haem detoxification pathway that is a metabolic checkpoint for parasite development, survival and reproduction. This provides a starting point for the development of novel therapies against such metazoan blood-feeders.
- Subjects :
- 0301 basic medicine
Pigments
Ancylostomatoidea
Male
Life Cycles
Erythrocytes
Physiology
Necator americanus
Toxicology
Pathology and Laboratory Medicine
Mice
Larvae
Medicine and Health Sciences
Aspartic Acid Endopeptidases
Nippostrongylus brasiliensis
lcsh:QH301-705.5
biology
Immunogenicity
Eukaryota
Body Fluids
Blood
Helminth Infections
Physical Sciences
Female
Nippostrongylus
Antibody
Anatomy
Detoxification
medicine.drug
Research Article
lcsh:Immunologic diseases. Allergy
Immunology
Materials Science
Antibodies, Helminth
Microbiology
03 medical and health sciences
Hookworm Infections
Immune system
Immunity
Virology
Helminths
parasitic diseases
Genetics
medicine
Parasitic Diseases
Animals
Molecular Biology
Hookworm infection
Materials by Attribute
Strongylida Infections
Hookworm vaccine
Life Cycle Stages
Organisms
Biology and Life Sciences
biology.organism_classification
Invertebrates
Gastrointestinal Tract
Mice, Inbred C57BL
030104 developmental biology
lcsh:Biology (General)
Hookworms
Antigens, Helminth
biology.protein
Parasitology
lcsh:RC581-607
Digestive System
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 15537374 and 15537366
- Volume :
- 14
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....52e52a47f84193f8dfffc85b68fee408