Zombie ant death grip due to hypercontracted mandibular muscles

Abstract

There are numerous examples of parasites that manipulate the behavior of the hosts that they infect. One such host-pathogen relationship occurs between the 'zombie-ant fungus' Ophiocordyceps unilateralis sensu lato and its carpenter ant host. Infected ants climb to elevated locations and bite onto vegetation where they remain permanently affixed well after death. The mandibular muscles, but not the brain, of infected ants are extensively colonized by the fungus. We sought to investigate the mechanisms by which O. unilateralis s.l. may be able to influence mandibular muscle contraction despite widespread muscle damage. We found that infected muscles show evidence of hypercontraction. Despite the extensive colonization, both motor neurons and neuromuscular junctions appear to be maintained. Infection results in sarcolemmal damage, but this is not specific to the death grip. We found evidence of precise penetration of muscles by fungal structures and the presence of extracellular vesicle-like particles, both of which may contribute to mandibular hypercontraction.

Genetic Underpinnings of Host Manipulation by Ophiocordyceps as Revealed by Comparative Transcriptomics

“…The destructive invasion and consumption of host tissues by Ophiocordyceps may have implications for behavior beyond mere host death. Notably, the ants’ muscles are affected, leading to muscle atrophy and hypercontraction that have been suggested to have a role in the locked biting position of manipulated ants ( Hughes et al 2011 ; Fredericksen et al 2017 ; Mangold et al 2019 ). In line with this aspect of the disease, a putative sarcalumenin gene was downregulated during live manipulation in both C. floridanus and C. castaneus (threefold and eightfold decrease from control to live manipulation, respectively) ( de Bekker et al 2015 ).…”

“…By interfering with big potassium (BK) channels, and, gamma amino butyric acid (GABA)-ergic and glutamatergic processes, aflatrem can induce muscle tremors, changes in activity level, and confusion ( Valdes et al 1985 ; Gant et al 1987 ; Yao et al 1989 ; Knaus et al 1994 ). Ophiocordyceps infected ants display comparable symptoms such as convulsions ( Hughes et al 2011 ), muscle hypercontraction ( Mangold et al 2019 ), and atypical exploratory behaviors ( de Bekker et al 2014b ) ( Figure 6 ).…”

“…As such, the study presented here seeks to home in on the major players involved in Ophiocordyceps infection and manipulation of carpenter ants by using a comparative transcriptomics framework to identify, compare, and discuss candidate genes underlying manipulation across two different fungus-ant species interactions. The species we compare are Ophiocordyceps kimflemingiae and its host Camponotus castaneus , on which mechanistic work has previously been performed ( de Bekker et al 2014b 2015; Fredericksen et al 2017 ; Mangold et al 2019 ; Loreto and Hughes 2019 ), and Ophiocordyceps camponoti-floridani ( Araújo et al 2018 ) and its host Camponotus floridanus . The interactions between the latter pair have not yet previously been investigated.…”

“…This final fatal change in behavior is the most tractable readout for manipulation of the host, and provides a growth and transmission site that appears to be adaptive for the fungal parasite ( Andersen et al 2012 ; Loreto et al 2014 ). Bioactive compounds with neuromodulatory and physiology-disrupting effects ( de Bekker et al 2014b 2015; Kobmoo et al 2018 ; de Bekker 2019 ; Loreto and Hughes 2019 ), and tissue destruction and hypercontraction of jaw muscles ( Hughes et al 2011 ; Fredericksen et al 2017 ; Mangold et al 2019 ) have been proposed as possible means of dysregulating host behavior. Moreover, manipulated biting appears to be synchronized by time of day in multiple Ophiocordyceps -ant species interactions ( Hughes et al 2011 ; de Bekker et al 2014a , 2015 , 2017b ; de Bekker 2019 ).…”

Genetic underpinnings of host manipulation byOphiocordycepsas revealed by comparative transcriptomics

“…Notably, the ants' muscles are affected, leading to muscle atrophy and hypercontraction , FREDERICKSEN & al. 2017, MANGOLD & al. 2019).…”