Descoberta abre caminho para encontrar genes que ajudam a Leishmania a causar doença

Dr. Stephen Beverley é co-autor do estudo que descobriu que a Leishmania, um parasita unicelular, é capaz de se reproduzir sexualmente

O parasita unicelular Leishmania pode se reproduzir sexualmente. É o que revela o artigo “Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania”. A descoberta pode abrir caminho para encontrar genes que ajudam o parasita a causar doenças. Estudando os parasitas híbridos e sua progênie recombinada, os pesquisadores serão capazes de mapear a localização em cromossomos de genes envolvidos em causar doença e resistir à resposta imune. Este mapa genético ajudará a entender por que algumas cepas causam uma doença pior do que outras e como fortalecer a resposta imune aos parasitas. Para saber mais sobre o assunto, a assessoria de comunicação da Sociedade Brasileira de Medicina Tropical (SBMT) entrevistou o Dr. Stephen M. Beverley, co-autor do artigo publicado em maio na PLOS Genetics.

Confira abaixo a entrevista na íntegra.

SBMT: Qual a importância da sua descoberta?

Dr. Stephen M. Beverley: The ability of organisms to mate, the mechanisms they use to do this, and the diversity of all of these in evolution, are a very popular topic of scientific investigation.

For pathogens as well as other organisms, mating provides the opportunity to generate new genotypes that may prove more ‘fit’ in evolution.

However, mating can also break up gene combinations that were quite successive. This is where microbes have a unique position since they have the option usually of propagating without mating or sex.

SBMT: Como foi realizado o teste para saber se os parasitas híbridos eram férteis?

Dr. Stephen M. Beverley: We took a hybrid parasite typically bearing 2 different/independent drug resistant parasites, and mixed them with either one of the original parental lines (back cross) or a different WT line (outcross).   The lines used in these crosses bore a 3rd independent drug resistance marker.

Since mating has so far only been described to occur during the parasite stages that occur in the sect vetor, the mixture was added to blood and then fed to sand flies through a thin membrane.

The flies were maintained long enough for the parasite developmental cycle within the fly to take place (2 weeks or less), and then the midguts were dissected and the parasites placed in culture.

At that time drug selections were applied to recover potential mating progeny – in the experiments above, it would be one of the markers from the hybrid, and one for the marker in the out or back cross.

If mating occurred, doubly drug resistant parasites would grow out, and be further characterized.

SBMT: O ciclo reprodutivo pode influenciar na virulência?

Dr. Stephen M. Beverley: Yes definitely. However as noted above mating can both create better more adaptive combinationds, but also break up ones. this is where microbes have an advantage as successful combinations can be propagated without sex.

SBMT: Como será possível saber se uma cepa provoca a forma leve da doença e outra causa a forma letal?

Dr. Stephen M. Beverley: We can use the information from the patient to predict this; more commonly we use various animal models of human disease and follow what happens to parasites in these.

SBMT: De que forma será feito o mapa genético?

Dr. Stephen M. Beverley: One first has a ‘physical map’ which these days most commonly is the genome sequence. As there are polymorphisms amongst the strains or species we use, we can map these onto the genome to generate ‘markers’. Then, we ask after mating occurs how often the markers are inherited together, or separately. The more often they cosegregate, the closer they are ‘genetically’. We then map the genetic distances onto the physical distances, to create a genetic map.

SBMT: A partir do mapa genético, o que se espera?

Dr. Stephen M. Beverley: Potentially we can use this to map virulence traits when we acquire more hybrids and phenotypes.

SBMT: Por que os parasitas híbridos raramente conseguem cruzar?

Dr. Stephen M. Beverley: This is something we are trying to understand. In other organisms mating is controlled by ‘mating type’ systems which act first to promote diversity by preventing self-mating, and perhaps that is what is happening in Leishmania. The other possibility is that there may be some advantage to preventing mating from occurring too frequently, so as to avoid breaking up good gene combinations.

SBMT: O senhor gostaria de acrescentar algo?

Dr. Stephen M. Beverley: I would like always to stress that this work is the fruit of a wonderful, long term collaboration with my colleague David Sacks at the NIH. David has been a pioneer in studying the biology of the parasite and insect vector hosts, and has invested tremendous work over the years to the point that he is really the leader. It has been our pleasure to be able to combine his expertise with ours in parasite genetics very productively.

Saiba mais sobre o Laboratório Beverley: http://beverleylab.wustl.edu/Research%20Page.html.