The life cycle and host manipulation mechanisms of Ophiocordyceps unilateralis sensu lato fungal species

Abstract

Ophiocordyceps unilateralis sensu lato species complex consists of parasitic fungi that infect insects (entomopathogens). Species within this complex infect ants and manipulate their behaviour to ensure successful fungal transmission. After infection, the ant’s normal behaviours change progressively, ultimately leading to death. The ant dies attached to vegetation in an elevated position where its mandibles are locked, in a position called ‘death grip’. The cadaver functions as a base for the development of the fungal sexual reproductive structure. From there, the fungus releases its spores to infect new foraging ants and continue its life cycle. This extreme host-parasite interaction has evolved over millions of years, during which the fungus has developed complex molecular and cellular strategies that it induces in its host. This literature review discusses the mechanical and chemical mechanisms by which fungi manipulate their hosts during their life cycle. Additionally, the infected ant’s behavioural changes are covered. Although these manipulation mechanisms have been widely researched, several uncertainties remain and they are discussed in this review. The mechanical mechanisms involve fungal infiltration of the ant’s muscle tissue, even individual muscle cells. The fungus utilizes nutrients and compounds form host tissues for its own metabolism with excessive tissue degradation occurring after the ant’s death. Mechanical colonization is suggested to induce convulsions in the infected ants, while infiltration and atrophy of mandible muscles may trigger the hypercontraction responsible for locked jaw in death grip. Notably, the fungus does not invade the ant’s brain, yet it still affects the ant’s neurological processes through chemically mediated pathways. The chemical mechanisms influence not only the ant’s neurology, but also its immunology, metabolism, circadian rhythm and muscle functions. Several fungal secreted compounds have been proposed to be contributors to behavioural manipulation. As secondary metabolites, enterotoxins may alter the host’s chemosensory functions leading to hyperactivity and hypercontraction during death grip, aflatoxins may induce staggering behaviour, and ergothioneine is suggested to protect the ant’s brain from inflammation. Fungal secreted proteins are suggested to modulate neurobiological processes, affect the host’s circadian clock and induce hyperactivity. However, many of these secreted molecules and their targeted pathways remain insufficiently understood. Ultimately, fungal colonization, secreted effectors and host tissue degradation together drive the manipulated behaviours that enhance fungal transmission and complete the reproductive cycle.