Plasma Membrane-Located Purine Nucleotide Transport Proteins Are Key Components for Host Exploitation by Microsporidian Intracellular Parasites
Microsporidians are highly reduced obligate intracellular eukaryotic parasites that cause significant disease in humans, animals and commercially relevant insects. Despite their medical and economic interest the mechanisms whereby microsporidians exploit the cells they infect are mainly unknown. We have characterised a conserved family of nucleotide transport proteins that we demonstrate have key roles in parasite biology. Microsporidians cannot synthesize the primary building blocks needed to make DNA and RNA for themselves, so they must import the starting materials from the infected host. We show that the microsporidian Trachipleistophora hominis, originally isolated from an HIV/AIDS patient, may achieve this by using four nucleotide transport proteins located in the plasma membrane of replicating intracellular parasites. In functional assays we demonstrate that all four proteins can transport radiolabelled adenine and guanine nucleotides. Genome analysis suggests that the imported nucleotides could be transformed by T. hominis into all of the critical purine-based building-blocks needed for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.
Vyšlo v časopise:
Plasma Membrane-Located Purine Nucleotide Transport Proteins Are Key Components for Host Exploitation by Microsporidian Intracellular Parasites. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004547
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004547
Souhrn
Microsporidians are highly reduced obligate intracellular eukaryotic parasites that cause significant disease in humans, animals and commercially relevant insects. Despite their medical and economic interest the mechanisms whereby microsporidians exploit the cells they infect are mainly unknown. We have characterised a conserved family of nucleotide transport proteins that we demonstrate have key roles in parasite biology. Microsporidians cannot synthesize the primary building blocks needed to make DNA and RNA for themselves, so they must import the starting materials from the infected host. We show that the microsporidian Trachipleistophora hominis, originally isolated from an HIV/AIDS patient, may achieve this by using four nucleotide transport proteins located in the plasma membrane of replicating intracellular parasites. In functional assays we demonstrate that all four proteins can transport radiolabelled adenine and guanine nucleotides. Genome analysis suggests that the imported nucleotides could be transformed by T. hominis into all of the critical purine-based building-blocks needed for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.
Zdroje
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