Specialist and Generalist Fungal Parasites Induce Distinct Biochemical Changes in the Mandible Muscles of Their Host

Abstract

Some parasites have evolved the ability to adaptively manipulate host behavior. One notable example is the fungus Ophiocordyceps unilateralis sensu lato, which has evolved the ability to alter the behavior of ants in ways that enable fungal transmission and lifecycle completion. Because host mandibles are affected by the fungi, we focused on understanding changes in the metabolites of muscles during behavioral modification. We used High-Performance Liquid Chromatography-Mass/Mass (HPLC-MS/MS) to detect the metabolite difference between controls and O. unilateralis-infected ants. There was a significant difference between the global metabolome of O. unilateralis-infected ants and healthy ants, while there was no significant difference between the Beauveria bassiana treatment ants group compared to the healthy ants. A total of 31 and 16 of metabolites were putatively identified from comparisons of healthy ants with O. unilateralis-infected ants and comparisons of B. bassiana with O. unilateralis-infected samples, respectively. This result indicates that the concentrations of sugars, purines, ergothioneine, and hypoxanthine were significantly increased in O. unilateralis-infected ants in comparison to healthy ants and B. bassiana-infected ants. This study provides a comprehensive metabolic approach for understanding the interactions, at the level of host muscles, between healthy ants and fungal parasites.

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“…Evidence for the disruption of the musculature stems from detailed microscopy work on Ophiocordyceps -infected ant heads at the time of manipulated summiting and biting behavior. These reports describe visual signs of fungal invasion, tissue degradation, and atrophy of manipulated ant mandible muscles (Fredericksen et al, 2017; Hughes et al, 2011; Mangold et al, 2019; Zheng et al, 2019). Future investigations documenting fungal growth and host tissue destruction at different stages and in body compartments beyond the head could be very insightful.…”

“…Corroborating evidence for the disruption of the musculature stems from detailed 25 microscopy work on Ophiocordyceps-infected ants at the time of manipulated summiting and biting behavior. These reports describe visual signs of fungal invasion, tissue degradation, and atrophy of manipulated ant mandible muscles [15,22,29,128].…”

“…Recent research into the mechanisms of parasitic manipulation by Ophiocordyceps have reported a number of fungal molecules and ant pathways that may be involved, including neuro-modulators and - protectants, insect hormones, feeding, locomotion, circadian rhythms and light-sensing, and muscular hyperactivity (de Bekker, Merrow, et al, 2014; de Bekker et al, 2015; de Bekker, 2019; de Bekker & Das, 2022; Kobmoo et al, 2018; Loreto & Hughes, 2019; Mangold et al, 2019; Trinh et al, 2021; Will et al, 2020; Zheng et al, 2019). Among these candidates, fungal proteins such as bacterial-like enterotoxins, protein tyrosine phosphatases, peptidases (e.g., S8 subtilisin-like serine proteases), and various undescribed small secreted proteins (uSSPs) may mediate important host-parasite PPIs.…”

“…Behavioral changes preceding this final summit could include host-adaptive responses, parasite-adaptive manipulations, or general symptoms of disease that span hyperactivity, uncoordinated foraging, decreased nestmate communication, and convulsions [9,[14][15][16][17]. While these modified ant behaviors have been observed in nature for some time [18], explorations of the fungal effectors involved are relatively more recent endeavors [14,[19][20][21][22][23][24][25]. These multi "-omics" studies have provided hypotheses about the parasite and host molecules that play a role in establishing the behavioral phenotypes observed, but leave their potential interactions open to interpretation.…”

“…A large number of fungal molecules and ant pathways may be involved in Ophiocordyceps behavioral manipulation, including neuro-modulators and -protectants, insect hormones, feeding, locomotion, circadian rhythms and light-sensing, and muscular hyperactivity 4 [14,17,19,21,22,[25][26][27][28][29]. Fungal proteins such as bacterial-like enterotoxins, protein tyrosine phosphatases, peptidases (e.g., S8 subtilisin-like serine proteases), and undescribed small secreted proteins (uSSPs) have been proposed as mechanisms of manipulation that presumably function by PPIs.…”