Plasma Membrane-Located Purine Nucleotide Transport Proteins Are Key Components for Host Exploitation by Microsporidian Intracellular Parasites

PLoS Pathogens

Christian Hacker¹  Sirintra Nakjang²  John M. Lucocq²  Eva Heinz²  Alison Gregory²  Alina V. Goldberg²  Edmund R. S. Kunji²  Robert P. Hirt²  Tom A. Williams³  T. Martin Embley⁴  John Mifsud⁴  Paul Dean⁵ 

[1] Department of Microbiology, Monash University, Melbourne, Victoria, Australia;Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom;Medical Research Council, Mitochondrial Biology Unit, Cambridge, United Kingdom;School of Medicine, University of St. Andrews, St. Andrews, United Kingdom;Victoria Bioinformatics Consortium, Monash University, Melbourne, Victoria, Australia

关键词: Cell membranes;    Membrane proteins;    Purines;    Pyrimidines;    Biological transport;    Parasitic diseases;    RNA transport;    Biosynthesis;   

DOI  :  10.1371/journal.ppat.1004547

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT) proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT) is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes), consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP) when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.

【 授权许可】

CC BY