In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 1 ( 2023-1-30), p. e1011129-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011129
DOI:
10.1371/journal.ppat.1011129.g001
DOI:
10.1371/journal.ppat.1011129.g002
DOI:
10.1371/journal.ppat.1011129.g003
DOI:
10.1371/journal.ppat.1011129.g004
DOI:
10.1371/journal.ppat.1011129.g005
DOI:
10.1371/journal.ppat.1011129.g006
DOI:
10.1371/journal.ppat.1011129.g007
DOI:
10.1371/journal.ppat.1011129.g008
DOI:
10.1371/journal.ppat.1011129.g009
DOI:
10.1371/journal.ppat.1011129.s001
DOI:
10.1371/journal.ppat.1011129.s002
DOI:
10.1371/journal.ppat.1011129.s003
DOI:
10.1371/journal.ppat.1011129.s004
DOI:
10.1371/journal.ppat.1011129.s005
DOI:
10.1371/journal.ppat.1011129.s006
DOI:
10.1371/journal.ppat.1011129.s007
DOI:
10.1371/journal.ppat.1011129.r001
DOI:
10.1371/journal.ppat.1011129.r002
DOI:
10.1371/journal.ppat.1011129.r003
DOI:
10.1371/journal.ppat.1011129.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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