BioEd Online

Researchers have finally shown that the parasite responsible for leishmaniasis does engage in sex, potentially opening up new opportunities for fighting the deadly disease.

The World Health Organization estimates that 12 million people are currently infected worldwide with widely differing forms of the disease, caused by Leishmania parasites. Some forms cause horrific skin infections, and others affect the internal organs and can cause death.

Leishmania parasites reproduce clonally and, despite some circumstantial evidence, there has been no proof that they can exchange genes through sex and form hybrids. "We could say circumstantial evidence is strong because we see apparent hybrids in nature, but that's not the same as saying one has or can attain a population-genetics proof. Formal experimental proof has been lacking," says Michael Miles, a Leishmania expert at the London School of Hygiene and Tropical Medicine.

Now David Sacks, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and his colleagues confirm the suspicions of many researchers by reporting evidence for Leishmania sexual recombination in a paper in Science¹.

"I think it's going to be a landmark paper in the field," says Joseph Heitman, who is director of the Center for Microbial Pathogenesis at Duke University in Durham, North Carolina, and was not involved in the research. "There are two impacts it will have. One is experimental; it provides a new tool kit for working with the organism. More theoretically, it's going to be very useful for looking at the population structure and at how that got to be," he says.

Hybrid hunt

Sacks and his team have now established that sand flies — a natural vector of Leishmania — are where the parasites reproduce. When flies were infected with two different strains of Leishmania that are resistant to two different drugs, hybrid parasites resistant to both drugs were later isolated from the flies, showing that the parasites had reproduced sexually.

In total, 18 hybrids were eventually recovered, each showing a full set of chromosomes from each parent plus additional genetic material called kinetoplast DNA from one parent.

One reason this hasn't been shown in Leishmania before might be down to the practical difficulties of studying its sand-fly vector in the lab. "It is likely [gene exchange] only occurs in the insect vector, and very few researchers have sand-fly colonies," says Sacks. "If sex only occurs in the flies, you have to have flies to investigate the problem."

A previous study² involving one of researchers behind the new paper, Stephen Beverley of the Washington University School of Medicine in St Louis, Missouri, did undertake the tricky investigation of Leishmania in sand flies in the lab almost 20 years ago, but found no hybrids. "We were convinced it had to occur because of all of those examples of hybrid genotypes from field samples," says Sacks.

Yet, Sacks explains, parasite sex is not the major method by which Leishmania reproduce. "Sex is rare. When it occurs, if it confers a powerful sexual advantage, then these lines will propagate clonally," he says.

Taxonomic tangle

This latest research could also help with understanding the diversity of natural populations of Leishmania. In a commentary that accompanies the research in Science³, Miles and his colleagues argue that several currently recognized species of Leishmania are probably not valid and that the taxonomy needs to be reassessed.

"The molecular genetic approach can show where species that are thought to be separate are actually very similar," he told Nature News.

Now that Leishmania hybrids have been created in the lab, researchers can bring traditional genetic approaches to bear on the parasite and track down the reasons behind some of the differences between strains, improving our understanding of disease virulence and drug resistance.

"We will, we hope, be able to take parental lines, do crosses in the lab and track the genes with those traits," says Sacks. "You could never do that with Leishmania before because we didn't have that tool."