title: Heme acquisition in the parasitic filarial nematode Brugia malayi.
abstract: Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter B. malayi HRG-1 (BmHRG-1) is indeed functional in B. malayi In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non-heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3-6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.-Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi.
authors.affiliation: New England BioLabs, Incorporated, Genome Biology Division, Ipswich, Massachusetts, USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Luck
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA; and.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yuan
authors.affiliation: New York Blood Center, Lindsley F. Kimball Research Institute, New York, New York, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Voronin
authors.affiliation: New England BioLabs, Incorporated, Genome Biology Division, Ipswich, Massachusetts, USA.
authors.forename: Barton E
authors.initials: BE
authors.lastname: Slatko
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA; and.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Hamza
authors.affiliation: New England BioLabs, Incorporated, Genome Biology Division, Ipswich, Massachusetts, USA; foster@neb.com.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Foster
mesh_terms: D000818:Animals; D017178:Brugia malayi; D017173:Caenorhabditis elegans; D006418:Heme / Q000276:immunology*; D006706:Homeostasis / Q000502:physiology*; D034622:RNA Interference
chemical_list: D006418:Heme
keywords:  iron metabolism; infectious disease; parasite metabolism