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Review the life cycle of an important human parasite

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The Cryptosporidium parasite, transmitted by water sources, is one of the most common causes of diarrheal disease worldwide. Credit: Muthgapatti Kandasamy and Boris Striepen

“We’ve had an interest in the romantic life of the Cryptosporidium parasite for some time,” says Boris Striepen, a scientist at Penn’s School of Veterinary Medicine.

Cryptosporidium is one of the leading causes of diarrheal disease in young children worldwide. The intestinal parasite contributes to infant mortality and causes malnutrition and stunted growth. How a parasite like this reproduces and completes its life cycle has a significant impact on the health of children.

“It’s the sex product of the parasite, which here is an infectious agent, a spore, that is transmitted through contaminated water,” Striepen explains. “So if you break his ability to have sex, you would break the cycle of transmission and infection.”

In a new article from PLOS Biology, Striepen and his colleagues in his lab are exploring new ways to understand how Cryptosporidium reproduces inside a host. Using an advanced imaging technique allowed scientists to observe the entire life cycle in the laboratory. They found that the parasite completed three cycles of asexual replication, then switched directly to male and female sexual forms. Their observations refute an intermediate stage introduced in the 1970s and fit well with the original description by physician and parasitologist Edward Tyzzer who discovered this pathogen more than a century ago.

“What we showed contradicts what you see in most textbooks today, including the description on the Centers for Disease Control and Prevention website,” Striepen says. “It’s really a super simple life cycle that is completed in a single host in three days and has only three characters: asexual cells, male cells and female cells.”

Other parasites, such as the malaria parasite Plasmodium, a “cousin” of Cryptosporidium, have more complicated and longer paths to follow a broadly similar life cycle. As Crypto completes its life cycle in a host, most malaria parasites move between two: a mosquito, where the parasite’s sexual reproduction occurs, and a human, where its asexual replication occurs.

“Cryptosporidium is an excellent model for studying parasite development; you can see steps analogous to what happens with the malaria parasite, but it’s much simpler because it all happens in just three days in a host, and we can observe it in simple cell cultures,” says Strepen.

In previous work on Cryptosporidium, Striepen and colleagues found that sexual reproduction seemed necessary for the parasite to move from one host to another to infect another, but also to maintain itself in a host during a chronic infection. Blocking the progression of development and sex of the parasite therefore presents itself as a strategy to cure or prevent infection.

Cryptosporidium is a tiny single-celled parasite that invades and reproduces inside the gut cells of its hosts. To get a closer look at what was going on, the researchers developed a live-cell microscopic imaging technique to follow the progression of the parasite over several days in cell cultures. Using genetic engineering, they added a fluorescent tag to the nucleus of each parasite, allowing them to observe the parasite’s replication in real time and distinguish the different stages of its life cycle.

What they saw was that the parasites “count to three,” says Striepen. Rather than responding to environmental cues, the parasites followed a rigid, built-in plan. After infecting a crop, the parasite underwent three cycles of asexual reproduction. Each cycle lasted about 12 hours, during which time the parasite established itself in the host cell and reproduced, resulting in eight new infectious parasites. These were then released to infect surrounding host cells.

After these three waves of amplification, their fate changes abruptly and they turn into male or female gametes, or sex cells, in a process that also lasted around 12 hours. By tracking individual parasites and their offspring, researchers have found no evidence of a specialized intermediate form assumed by many textbooks, demonstrating direct development.

Interestingly, the parasite seemed pre-committed to its future fate and carried that blueprint from host cell to host in ways not yet understood.

Researchers were intrigued to see that both males and females come from the infectious forms released by the same asexual parasites. “One of the really interesting things about gender identity here is that it’s not inherited and hard-wired into the genome, but much more fluid,” Striepen says. “There’s an asexual cell that divides into genetically identical clones, and then those clones somehow become male or female on the fly, resulting in radically different cell shape and behavior.”

Future research will focus on the molecular mechanism of commitment to understand how this life cycle is programmed into the biology of the parasite. Understanding Cryptosporidium’s life cycle is key to thinking about how to create a vaccine or therapy for the disease, Striepen says.

“How cells make decisions and carry out developmental plans is one of the most fundamental questions in biology. Cryptosporidium offers a tractable system to better understand this mechanism in parasites. Hopefully, we can gain insights that contribute to the understanding of cryptosporidiosis and malaria and pave the way for urgent new interventions for these important diseases.


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More information:
PLOS Biology (2022). journals.plos.org/plosbiology/ … journal.pbio.3001604

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Reviewing the life cycle of an important human parasite (2022, April 15)
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