|Dead ants infected with Ophiocordyceps unilateralis|
(Tul.) Petch (1931)
Torrubia unilateralis Tul. (1865)
Ophiocordyceps unilateralis is an entomopathogenic fungus predominantly found in tropical forest ecosystems. Also known as "zombie fungi," it was first discovered by British naturalist Alfred Russel Wallace in 1849. In order to increase its own fitness O. unilateralis utilizes the evolutionary trait of an extended phenotype to manipulate the behavioral patterns of an infected ant, specifically Camponotus leonardi of the tribe of campotini. The infected ants leave their canopy nest and foraging trails, heading for the forest floor in search of an area with a temperature and humidity level that is suitable for fungal growth. The infected ant will then use its mandible to affix themselves to a major vein on the underside of a leaf and eventually die.
The species can be identified at the end of its lifecycle by its reproductive structure, consisting of a wiry yet pliant darkly pigmented stroma stalk extending from the back of the deceased ant's head. The stalk has perithecia just below its tip. The fungus infects ants, most known as the carpenter ants, in which the fungus creates a single stalk arising from the dorsal neck region on which the sexual structures are borne horizontally, which creates the spores. Once infected with the fungus the ant will climb down from its normal habitat and bite down on the underside of a leaf. This is known as "the death grip" occurring in very precise locations.
Like other fungi pathogenic to insects in the Ophiocordyceps genus, O. unilateralis targets a specific host species, the Camponotus leonardi ant. However the fungus may parasitize other closely related species of ants with lesser degrees of host manipulation and reproductive success.
The fungus's spores attach to the ant, eventually breaking through the exoskeleton using mechanical pressure and enzymes. Yeast stages of the fungus spread in the ant's body and presumably produce compounds that affect the ant's hemocoel and utilizes the evolutionary trait of an extended phenotype to manipulate the behavioral patterns exhibited by the ant. These infected ants begin to have irregularly spaced full body convolutions which sends them to the forest floor. The insect climbs up the stem of a plant and uses its mandibles to secure itself to a leaf vein, with abnormal force, leaving dumbbell-shaped marks on it. A search through plant fossil databases revealed similar marks on a fossil leaf from the Messel Pit which is 48 million years old. Once the mandibles of the ant are secured to the leaf vein, atrophy quickly sets in destroying the sarcomere connections in the muscle fibers, and reduces the mitochondria and sarcoplasmic reticula. The ant is no longer able to control the muscles of the mandible and will remain affixed here. This lockjaw trait is popularly known as the death grip, and is essential in the fungus's fitness.
The fungus then kills the ant, and continues to grow as its hyphae invade more soft tissues and structurally fortify the ant's exoskeleton. More mycelia then sprout out of the ant, and securely anchor it to the plant substrate while secreting antimicrobials to ward off competition. When the fungus is ready to reproduce, its fruiting bodies grow from the ant's head and rupture, releasing the spores. This process takes 4 to 10 days.
The changes in the behavior of the infected ants are very specific, giving rise to the popular term "zombie ants," and tuned for the benefit of the fungus. The ants suffer from convulsions causing them to fall to the ground and preventing them from finding their way back to their canopy. The ants generally clamp to a leaf's vein at a mean height of 25.20 ± 2.46 cm above the forest floor, on the northern side of the plant, in an environment with 94–95% humidity and temperatures between 20 and 30 °C (68 and 86 °F). Infections may lead to 20 to 30 dead ants per square meter. "Each time, they are on leaves that are a particular height off the ground and they have bitten into the main vein [of a leaf] before dying." When the dead ants are moved to other places and positions, further vegetative growth and sporulation either fails to occur or results in undersized and abnormal reproductive structures.
O. unilateralis has been known to destroy entire ant colonies. In response, ants have evolved the ability to sense that a member of the colony is infected; healthy ants will carry the dying one far away from the colony in order to avoid fungal spore exposure.
Throughout the life cycle, there are unique challenges that must be met by equally unique metabolic activities. The fungal pathogen must attach securely to the arthropod exoskeleton and penetrate it—avoiding or suppressing host defenses—then, control the behavior of the host before killing it; and finally, it must protect the carcass from microbial and scavenger attack.
The Ophiocordyceps fungus contains various known and untapped bioactive metabolites, and is being investigated as a new source of natural drugs with immunomodulatory, antitumor, hypoglycemic and hypocholesterolemic functions.
Six bioactive naphthoquinone derivatives have been isolated from O. unilateralis, namely
- 4-O-methyl erythrostominone
- deoxyerythrostominol, and
- 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-1,4-naphthoquinone showed anti-malarial activity in vitro.
There has also been research into the use of red naphthoquinone pigments made by O. unilateralis as a dye for food, cosmetic and pharmaceutical manufacturing processes.
O. unilaterlis produces naphthoquinone, which under acidic conditions show red and under basic conditions show a purple color. These pigments are stable against acid/ alkaline conditions, light and non-cytotoxic, which makes them applicable food coloring as well as dyeing of other materials. These attributes also make it a prime candidate for anti-tuberculoid testing in secondary TB patients, by improving symptoms and enhancing immunity when combined with chemotherapeutic drugs. 
O. unilateralis suffers from an unidentified fungal hyperparasite, reported in the lay press as the "anti-zombie-fungus fungus," that results in only 6–7% of sporangia being viable, limiting the damage O. unilateralis inflicts on ant colonies.The hyper-parasite moves in to attack Ophiocordyceps unilateralis as the fungal stalk emerges from the ant's cadaver. This can stop the stalk from releasing its spores. 
The density of infected ants and graveyards of dead ants are numerous and spread throughout the surrounding area of the colony. Even though O. unilateralis is very virulent, only about 6.5% of all fruiting bodies are viable spore-producers. This is caused by the castration of the fungus by the hyperparasite which may cause the limiting of the viable infectious spores. Ants also groom each other to combat microscopic organisms that could potentially harm the colony. This shows that the colony is not in as much danger as previously thought. Additional fungi have also shown beneficial assistance to the colony as well.
In popular culture
A fictitious variant of the fungus is featured in the game The Last of Us. The infection spreads to humanity and creates a zombie-like appearance/behavior, which causes the infected to become hostile and violent towards the non-infected.
A mutation of this fungus appears in the M.R. Carey (aka Mike Carey) novel "The Girl with all the Gifts" published by Orbit books UK 1/2014 US 6/2014.
In the television series The Simpsons episode "The Man Who Grew Too Much" (season 25, episode 13), Sideshow Bob reveals that he has spliced his DNA with O. unilateralis, and that as a consequence he can be tipped into a murderous rage by the slightest provocation.
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