Revising the lifecycle of an important human parasite

Date:
April 19, 2022
Source:
University of Pennsylvania
Summary:
Researchers have tracked Cryptosporidium in real time, creating
a new paradigm for how the widespread parasite reproduces in a host.



FULL STORY ==========================================================================
"We have been interested in the romantic life of the
parasiteCryptosporidiumfor some time," says Boris Striepen, a scientist
in Penn's School of Veterinary Medicine.


========================================================================== Cryptosporodiumis a leading cause of diarrheal disease in young children
around the world. The intestinal parasite contributes to childhood
mortality and causes malnutrition and stunting. How a parasite like this
one reproduces and completes its life cycle has significant impact on
child health.

"It's the product of parasite sex, that is infectious agent here, a spore,
that is transmitted by contaminated water," Striepen says. "So, if you
break its ability to have sex, you would break the cycle of transmission
and infection." In a new paper in PLOS Biology, Striepen and colleagues
in his lab tread new ground in understanding how Cryptosporidiumreproduces inside a host. Using an advanced imaging technique allowed the scientists
to observe the entire lifecycle in the laboratory. They found the parasite completes three cycles of asexual replication and then directly switches
to male and female sexual forms.

Their observations refute an intermediate stage that was introduced in
the 1970s and align well with the original description of physician and parasitologist Edward Tyzzer who discovered this pathogen more than a
century ago.

"What we have shown contradicts what you see in most textbooks today,
including the description at the Centers for Disease Control and
Prevention website," Striepen says. "It's really a super simple
lifecycle that is completed in a single host in three days and only
has 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 lengthy paths to follow an
overall similar life cycle. While Crypto completes its lifecycle in one
host, most malaria parasites move between two: a mosquito, where the
parasite's sexual reproduction occurs, and a human, where its asexual replication occurs.



========================================================================== "Cryptosporidiumis a great model to study parasite development; you can
see analogous steps to what happens with the malarial parasite, but it's
much simpler because it all happens over only three days in one host,
and we can observe it in simple cell cultures," Striepen says.

In earlier work on Cryptosporidium, Striepen and colleagues had found
that sexual reproduction appeared necessary for the parasite to move from
one host to infect another but also to sustain itself in a host during
chronic infection. Blocking developmental progression and parasite sex
thus presents itself as a strategy to cure or prevent infection.

Cryptosporidium is a minuscule single-cell parasite that invades and
reproduces within the cells of the intestine of its hosts. To get a
closer look at what was happening, the researchers developed a live-cell microscopic imaging technique to track the progression of the parasite
through multiple days in cell cultures. Using genetic engineering they
added a fluorescent label to the nucleus of each parasite, allowing
them to observe the replication of the parasite in real time and to
distinguish its different lifecycle stages.

What they saw was the parasites "count to three," says Striepen. Rather
than responding to environmental cues, the parasites followed a rigid
built-in plan.

After infecting a culture, the parasite underwent three cycles of asexual reproduction. Each cycle took about 12 hours, during which the parasite established a home within the host cell and replicated itself resulting
in eight new infectious parasites. Those were then released to infect surrounding host cells.

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



========================================================================== Interestingly, the parasite appeared pre-committed to their future fate
and carried that plan from one host cell into the next in a way not
yet understood.

The researchers were intrigued to see that male and females arise from
the infectious forms released from the same asexual parasites. "One of
the really interesting aspects of sexual identity here is that it is not inherited and hard-wired in the genome but much more fluid," Striepen
says. "There's an asexual cell that divides itself into genetically
identical clones, and then those clones somehow become male or female on
the fly, resulting in dramatically 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 parasite's biology.

Understanding the life cycle of Cryptosporidiumis critical in thinking
about how to create a vaccine or therapy for the disease, Striepen says.

"How cells make decisions and execute 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 lead the way to new urgently needed interventions for
these important diseases." Boris Striepen is the Mark Whittier and Lila Griswold Allam Professor of Microbiology and Immunology at the University
of Pennsylvania School of Veterinary Medicine.

Striepen's coauthors were lab members Elizabeth D. English, Amandine
Gue'rin, and Jayesh Tandel.

The study was supported by grants from the National Institutes of Health
to Striepen and a postdoctoral fellowship from the European Molecular
Biology Organisation to Gue'rin.


========================================================================== Story Source: Materials provided by University_of_Pennsylvania. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Elizabeth D. English, Amandine Gue'rin, Jayesh Tandel, Boris
Striepen.

Live imaging of the Cryptosporidium parvum life cycle reveals direct
development of male and female gametes from type I meronts. PLOS
Biology, 2022; 20 (4): e3001604 DOI: 10.1371/journal.pbio.3001604 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220419170752.htm

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