Hybrid strains make Trypanosoma cruzi more dangerous
Researchers have mapped out how the parasite forms new variants that are more effective at escaping the immune system and developing disease14/06/2022
More than a century after having been described by science and with about 7 million people currently infected in the world, scientists achieve important results that can help in the control of Chagas disease. A new study published in the journal eLife titled “Microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid genome diversification” shows how the parasite Trypanosoma cruzi forms new variants that are more effective at bypassing the immune system and causing Chagas disease, a major problem in Central and South America. Researchers have also found that there is great exchange of genetic material in a process known as genetic recombination. The work is the result of a great collaboration between the Karolinska Institutet in Stockholm, scientists from the London School of Hygiene and Tropical Medicine (LSHTM) and the Federal University of Santa Catarina (UFSC) in Brazil.
The study is based on parasite strains that spontaneously formed hybrids in a laboratory setting. The researchers isolated DNA from the parental parasites and several of their offspring and mapped the entire genome through large-scale DNA sequencing. Research has revealed that hybrids contain all of both parents DNA initially, but the amount of DNA gradually decreases and eventually ends up at the right level. It was also revealed that there is a significant exchange of genetic material, called genetic recombination. By mapping the genome of parental lines and their offspring over time, researchers have a detailed picture of how hybrids are formed. The exchange of genetic material can generate new genetic variants that make the parasite more harmful.
The teams findings should be celebrated by the scientific community, as they can give rise to new methods to diagnose, prevent and treat Chagas disease, a silent and neglected tropical disease, whose existing medications are few, cause many side effects and are not suitable for all stages of the disease. The main researcher, Dr. Björn Andersson, professor of genome analysis at the Department of Cell and Molecular Biology at Karolinska Institutet, points out that the hybrids studied by genome sequencing can be used in future researches to elucidate other aspects of hybrid formation, including protein expression and particular pathways.
Studies in the last two decades have shown the existence of material exchange between different strains of T. cruzi, which may indicate sexual reproduction and the consequent increase in genetic variability. To reproduce in this way, parasites benefit from double-stranded DNA breakage. Asked if he believes that strains with hybrid genetic material have a higher expression of proteins linked to DNA breakage, Dr. Björn explains that his team (and others) showed that there is frequent recombination in T. cruzi, especially in repetitive regions of the genome, which also contain surface molecule genes, as well as a large number of retrotransposons. “As we have clearly demonstrated, there is a genetic exchange in T. cruzi, through hybrid formation. There are some indications that other types of exchange may occur, including sexual. We see signs of increased mutation and recombination frequencies in T. cruzi hybrids, he adds. However, according to him, so far there is no specific data on the expression of individual proteins. “Recombination activity can be of great importance, since it can produce offspring with entirely new variants of surface molecules. These descendants can thus be more viable and more pathogenic in the host,” he emphasizes.
Asked if the discovery of his team in relation to Trypanosoma cruzi may apply to other trypanosomatids, such as Trypanosoma brucei, the causative agent of sleeping sickness, prevalent in Africa, which depends on a process in which one gene needs to be exchanged for another so that it escapes the hosts immune system, Dr. Björn points out that there are huge differences in the biology of the different pathogenic trypansomatids. “This includes immune evasion mechanisms as well as many other biological processes. The surface molecules of T. cruzi do not change and many are expressed at the same time, completely differently from T. brucei“, he alerts. Also according to the researcher, the genetic variation is very large in families of large surface molecules. Besides, the genetic exchange seems to be different, and the T. brucei apparently exhibits greater sexual reproduction.
The next step is to study material from nature and patients to get a more detailed picture on how the parasite varies its genes. The team is also working to improve the diagnosis of Chagas disease in Bolivia.
Small parasite capable of causing severe disease
Chagas disease or American trypanosomiasis is the infection caused by the protozoan Trypanosoma cruzi. It is found in 21 countries in Latin America, the United States, Japan, Australia, and some countries in Europe. In Brazil, it is the fourth leading cause of death among infectious-parasitic diseases. According to data from the Pan American Health Organization (PAHO), more than 8 million people live with the disease in Latin America. The data are even more alarming when it is found that about 70% of these people are unaware of the infection, due to the little apparent symptoms. Although silent, Chagas disease kills about 10 thousand people a year in the region and about 75 million people are at risk of becoming infected. A person can live for years, sometimes a lifetime, without knowing about the disease. Only 30% of individuals with the disease are diagnosed and about 1% have access to appropriate medicines each year. If left untreated, it can cause irreversible damage to the heart and other vital organs, compromising life at work and perpetuating cycles of poverty.
The life cycle begins when the parasite enters the persons bloodstream and invades the cells, becoming an amastigote, which is the stage of development and multiplication. Amastigotes can continue to invade cells and multiply, but they can also evolve to trypomastigotes, destroy cells, and remain circulating in the bloodstream. A new cycle can begin when the kissing bug bites an infected person and acquires that parasite. The trypomastigotes in the kissing bug become epimastigotes, multiply and become trypomastigotes again, which are released in the feces of this insect.