How The Blue Blood Of The Horseshoe Crab Is Helping Us Detect Bacteria Beyond Earth

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“Blue blood of a crab-arachnid in space to detect possible infections of an astronaut in full galactic mission. ” If this has not caught your attention: Houston, we seem to have a serious problem. As crazy as this first idea may seem, we would not try to make curiosity knock on your door without a good argument. In fact, the statement you just read is true and the blood of the animal you are referring to, is much more important than it seems.

Despite its name, do not be fooled, it is neither a crab, nor has a horseshoe shape. In fact, at first glance it may seem more like a small species of stingray with a built-in shell or even one of those robot vacuum cleaners that leave your living room unpolluted. It could easily be part of the cast of ‘Star Wars’ alien creatures. As you can imagine, its shape is far from what we would think when talking about a conventional crab.

Disturbing as well as disconcerting, this could be the presentation and a first contact with the Limulus polyphemus, known by his relatives, effectively, as a horseshoe crab. “There are five species of these animals, the most common are distributed along the Atlantic coast of the United States and can be observed in the spawning periods, in the sand, on the shores of the sea,” explains Xakata Begoña Sánchez Chillón, conservative of arthropods of the National Museum of Natural Sciences. “The rest of the species are distributed in East and Southeast Asia, where due to their great exploitation they are at high risk of extinction, ” he adds.

But then, is it a crab or not? As we anticipated, no. According to this study, published in 2019 in the scientific journal Systematic Biology , despite belonging to the group of arthropods, the horseshoe crab family is closer to arachnids than to crustaceans . To make it more visual: throw spiders more than crabs. “Of course, unlike spiders, it has 6 pairs of appendages and an exoskeleton or shell that constitutes the union of the head and thorax,” says Sánchez.

“Currently, the comparison of thousands of genes has revealed this new hypothesis , ” he told Xataka Jesus A. Ballesteros, researcher at the Department of Integrative Biology at the University of Wisconsin-Madison (USA) and one of the study authors. “These results require scrutiny and corroboration, but they reveal a part of the complexity of the evolutionary process ; the same processes that have shaped and continue to shape the tree of life of which we are part,” he adds.

But it is not the name or form of this curious animal that makes us write about it today, but its blood , both for its appearance and for its medical applications. According to Sánchez, the primitive enzymes this animal attack the material of the cell walls of most bacteria , so they are frequently used in tests to detect bacterial endotoxins in numerous pharmaceutical products.

What is special about the horseshoe crab’s blood?

As if it were a member of royalty, the blood of our protagonist is blue . While the human is red by a pigment of this color, hemoglobin, and its corresponding iron content; its analogue in this arthropod causes its hemolymph to acquire a different hue.

“Hemocyanin (which contains copper instead of iron) is the one that gives blue color to the blood of the horseshoe crab,” explains Xataka Susana Enriquez, a researcher at the Institute of Marine Sciences and Limnology (ICML) of the National Autonomous University of Mexico . “But the value of this bug’s blood resides in cells called amebocytes , which function as their immune system: when they come in contact with endotoxins produced by pathogenic bacteria, they solidify to” alert “that” there is work to be done “and start counteracting an infection . “

“These compounds [endotoxins] are very abundant in the membranes of gram-negative bacteria, which are the majority of those that live in the marine environment,” says Xataka Gema Hernández-Milia, a biologist specializing in marine mammal food ecology. “They could be compared to the pieces of a puzzle: the enzymes in their blood cells coincide with the endotoxins and bind to them, creating a clot that prevents the consequences of the bacteria,” he adds.

Since being studied, the blood of this crab has been a revolution in the world of medicine . In fact, if you’ve ever had a flu shot or know someone with a pacemaker, you owe the animal one.

According to the Horseshoes Crab website , developed by the Ecological Research and Development research group, a non-profit organization that has been fighting to conserve the four species of horseshoe crab since 1995, “the quality of vaccines, injectable medications, intravenous solutions and medical implants are checked using the blood of this crab. ”

In addition, the Food and Drug Administration (FDA) has used it since 1970 (the year until rabbit blood was used in this task) to approve medications , making sure they are free of endotoxins. Why? We tell you his story.

Although shallow, the sandy seabed in which the arthropod inhabits, along the east coast of North America and Central America, are often plagued with bacteria . Their own habitat, therefore, poses a threat in itself: in other circumstances, these microorganisms could cause all kinds of infections. Here is the survival key of our protagonist of blue blood.

The primitive immune system of this distant relative of the trilobites is based on a blood coagulation mechanism that protects it from the endotoxins to which it is continuously exposed. “The blood cells of the horseshoe crab, the amebocytes, contain proteins that are released in response to the presence of unwanted organisms, such as gram-negative bacteria. In this way, they get their blood to clot around the lesion and bacteria, protecting the animal, ”the authors explain on the web.

That is, the bacteria are trapped and unable to continue advancing through your body.

This defense mechanism, which was recorded for the first time as early as 1885 and which was studied in depth since the 1950s, is known as Limulus amebocyte lysate (LAL). Its effectiveness is such that it can detect the contamination with endotoxins of Gram-negative bacteria in incredibly low concentrations.

But what does blue blood have to do with space?

We return to the beginning, to our eccentric and first statement: ” Blue blood of crabs- arachnids in space to detect the possible diseases of an astronaut in full galactic mission.” For now, we give the okey to the first concept, but what about the rest? What does this substance have to do with space, astronauts and disease detection?

NASA, through this article on its website, puts us in a situation: “Imagine an astronaut on a space mission to Mars, halfway from Earth, which begins to feel bad. His throat hurts and he seems to have a fever, but he does not want to get sick or infect his companions. Should I take an antibiotic? And if so, what kind?

As a solution to this question, NASA’s Marshall Space Flight Center developed the LOCAD-PTS (Lab-on-a-Chip Application Development-Portable Test System), a portable device that allows rapid detection of gram- negative pathogenic bacteria in space thanks to the LAL. How?

How The Blue Blood Of The Horseshoe Crab Is Helping Us Detect Bacteria Beyond Earth

“Thanks to this machine, a possible infection can be detected much faster than it would be to wait for the results of a culture in a Petri dish,” explains Enriquez. According to NASA; lets you know if certain types of bacteria are present on the surfaces of space stations.

“The reaction occurs with the endotoxins found in the membrane of these bacteria or some fungi (the same happens with the profenoloxidase of the Jonah crab) that allow to detect gram-positive bacteria,” he explains to Xataka Hector Socas Navarro, a physicist at the Institute of Astrophysics of the Canary Islands and director of the Museum of Science and Cosmos of Tenerife. “These enzymes go in different cartridges of the system, with which the collected sample is reacted,” he says.

But its usefulness does not end here: the system not only locates a possible infection, but indicates what type of antibiotics would be necessary to combat such bacteria. “It was an interesting development: gram-negative bacteria are among the most pathogenic, responsible for many respiratory, urinary and gastrointestinal diseases in humans,” says Enriquez. In addition, he adds, it is the “resistant” ones that cause the most problems in hospitals.

This test is useful for the astronaut who feels that he is beginning to have health problems. Thanks to it, he can check the causes of the discomfort quickly and stop the infection (if any) at an early stage , long before the disease develops and he himself was a source of bacteria for his companions.

According to Enriquez, when the infection is still incipient, the culture in Petri dishes is not as effective or, at least, it requires more time for the crop to grow and confirm what type of bacteria is growing. As a result, the diagnosis comes later, making the infection more likely to be greater , not only within an astronaut, but within the ship for the entire crew. “I think it is a potentially useful tool to quickly slow down the progress of possible infections by gram-negative bacteria,” he concludes.

In the words of Socas, this system was also used between 2006 and 2009 to investigate the presence of bacteria and fungi in different places of the International Space Station (ISS). Afterwards, this technique stopped being used, giving way to more sophisticated methods (the PTS did not allow to identify which microorganisms had been detected, something that is possible today with molecular analysis technologies).

“Currently, experiments are being carried out with polymerase chain reaction (PCR) that allow amplifying any piece of DNA that is present: make many copies of the fragment and facilitate its detection,” Socas says. Several experiments between 2015 and 2016 have allowed us to know more about these bacteria and fungi. “The dominant population of microorganisms is associated with the human microbiome , although there may also be opportunistic pathogens.”

To avoid confusion, Socas insists that we talk about terrestrial microbes dragged by the missions themselves and the astronauts who have gone to the ISS. “Their study is important in order to understand the possible extension of microorganisms carried by humans in future missions and to the health of astronauts, especially considering that there appear to be effects on the immune system of prolonged permanence in space.”

In fact, the US National Research Council recommends in the ten-year review of its committee of biological and physical sciences of space that NASA establish a large-scale microbial observation program at the ISS.

Does the horseshoe crab survive after bleeding?

In order to obtain the liquid gold that supposes the blood of the horseshoe crab, the companies capture adult specimens of this species, extract a third of their total blood and release them again. “However, these species of xiphosuros have to pay a very high price, since death during the process occurs in about 15% of individuals, ” says Sánchez. Some reports also indicate that this mortality may be even higher due to bad practices during collection and transportation .

How The Blue Blood Of The Horseshoe Crab Is Helping Us Detect Bacteria Beyond Earth

“This, together with the influence that climate change is having on the seas, makes the four species that exist today are in a serious and growing danger of extinction, ” he adds.

According to the Ecological Research and Development Group, in 2016 the mortality associated with the production of LAL was around 70,600 animals per year , which shows that the species decreases worldwide given its great use for biomedical tests.

To avoid the possible disappearance of the horseshoe crab, which would be a great loss due to its ecological, agro-livestock and fishing interest , as well as biomedical, studies like this, published in 2018 in the scientific journal PLOS Biology , have investigated similar options, thanks to the that you could enjoy a synthetic alternative to this substance. Unlike LAL, the technique (recombinant Factor C, rFC) would use a cloned arthropod protein as an active ingredient.

“The proven efficacy of this alternative to detect endotoxins is an opportunity for the pharmaceutical industry to modernize its procedures and contribute to the conservation of horseshoe crabs,” the authors explain at the conclusion of the research: using the CFR would reduce the 90 % in the demand for LAL. That is, the mortality of the horseshoe crab would decrease , according to the research, by about 100,000 specimens annually in North America alone. “It is a more humane and more ecologically sustainable method,” they conclude.

 

Source: Xataka