Stealing is the deal

Parasites that grow within animal cells use a family of transport proteins to take nucleotides, the building blocks of DNA, from their hosts.

Microsporidia with either NTT proteins (left) or MFS proteins (right) shown in red on the surface of the parasite. Image credit: Peter Major and Paul Dean (CC BY 4.0)

Microsporidia are a group of microscopic parasites that spend part of their lives inside the cells of a broad range of animal hosts, including humans. These parasites are considered to be related to fungi, some of which also live within the cells of other species and are known as fungal endoparasites. One of the shared characteristics of these parasites is that they cannot make nucleotides, molecules that are both the main source of energy of the cell and also the building blocks of DNA. Instead, they take nucleotides, or the materials needed to make nucleotides, from their host cells. Once Microsporidia have depleted a host cell, they turn into spores that can survive outside the host until they invade a new cell, starting the cycle anew.

Microsporidia have proteins on their surface, including nucleotide transporter family proteins (NTT), that enable them to import nucleotides from their host into themselves. Although most fungal endoparasites are also thought to steal nucleotides from their hosts, many do not have NTT proteins, raising the question of how they import the nucleotides. A group of proteins called the Major Facilitator Superfamily (MFS) consists of proteins that were thought to transport the materials cells need to make nucleotides (which are also called nucleotide precursors). Members of this family are found throughout Microsporidia and related fungal endoparasites.

These proteins could explain how fungal endoparasites take nucleotides from their hosts. To test this hypothesis, Major et al. infected mammalian cells with Microsporidia and then checked where two MFS proteins were located during infection. This showed that the proteins were on the surface of the endoparasites, implying that they could be nucleotide precursor transporters. Next, Major et al. genetically modified Escherichia coli bacteria so they would produce MFS proteins, and showed that the proteins could transport two types of nucleotides. Together these results show that MFS proteins could be responsible for nucleotide transport in fungal endoparasites.

In addition to humans, Microsporidia and related fungal endoparasites infect a wide range of animals, including pollinating insects, which have ecological and economic importance. Given that Microsporidia can only survive if they take nucleotides from their hosts, knowing more about the proteins that import the nucleotides could lead to new cures for Microsporidia infections.