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Haem transporter HRG-1 is essential in the barber’s pole worm and an intervention target candidate
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Haem transporter HRG-1 is essential in the barber’s pole worm and an intervention target candidate
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Journal Article
Haem transporter HRG-1 is essential in the barber’s pole worm and an intervention target candidate
2023
Overview
Parasitic roundworms (nematodes) have lost genes involved in the de novo biosynthesis of haem, but have evolved the capacity to acquire and utilise exogenous haem from host animals. However, very little is known about the processes or mechanisms underlying haem acquisition and utilisation in parasites. Here, we reveal that HRG-1 is a conserved and unique haem transporter in a broad range of parasitic nematodes of socioeconomic importance, which enables haem uptake via intestinal cells, facilitates cellular haem utilisation through the endo-lysosomal system, and exhibits a conspicuous distribution at the basal laminae covering the alimentary tract, muscles and gonads. The broader tissue expression pattern of HRG-1 in Haemonchus contortus (barber’s pole worm) compared with its orthologues in the free-living nematode Caenorhabditis elegans indicates critical involvement of this unique haem transporter in haem homeostasis in tissues and organs of the parasitic nematode. RNAi-mediated gene knockdown of hrg-1 resulted in sick and lethal phenotypes of infective larvae of H . contortus , which could only be rescued by supplementation of exogenous haem in the early developmental stage. Notably, the RNAi-treated infective larvae could not establish infection or survive in the mammalian host, suggesting an indispensable role of this haem transporter in the survival of this parasite. This study provides new insights into the haem biology of a parasitic nematode, demonstrates that haem acquisition by HRG-1 is essential for H . contortus survival and infection, and suggests that HRG-1 could be an intervention target candidate in a range of parasitic nematodes.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans Proteins - genetics
/ Caenorhabditis elegans Proteins - metabolism
/ Enzymes
/ Gonads
/ Haem
/ Heme
/ Identification and classification
/ Larvae
/ Mammals
/ Medicine and Health Sciences
/ Membrane Transport Proteins - metabolism
/ Muscles
/ Nematoda
/ Proteins
/ Research and Analysis Methods
/ Survival
