Neurotransmitter acetylcholine mediates the mummification of Ophiocordyceps sinensis -infected Thitarodes xiaojinensis larvae

Abstract

ABSTRACT Parasites can manipulate host behavior to facilitate parasite transmission. One such host–pathogen interaction occurs between the fungus Ophiocordyceps sinensis and the ghost moth Thitarodes xiaojinensis. O. sinensis is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown. We characterized the small molecules regulating host behaviors and the altered metabolites in infected and mummified host larvae. Lipid-related metabolites, such as phosphatidylcholine, were identified in infected and mummified larvae. Decreased levels of the neurotransmitter acetylcholine (ACh) and elevated choline levels were observed in the brains of both the infected and mummified larvae. The aberrant activity of acetylcholinesterase (AChE) and relative mRNA expression of ACE2 (acetylcholinesterase) may mediate the altered transformation between ACh and choline, leading to the brain dysfunction of mummified larvae. Caspofungin treatment inhibited the mummification of infected larvae and the activity of AChE. These findings indicate the importance of ACh in the mummification of host larvae after O. sinensis infection. IMPORTANCE Ophiocordyceps sinensis -infected ghost moth larvae are manipulated to move to the soil surface with their heads up in death. A fruiting body then grows from the caterpillar’s head, eventually producing conidia for dispersal. However, the underlying molecular and chemical mechanism has not been characterized. In this study, we describe the metabolic profile of Thitarodes xiaojinensis host larvae after O. sinensis infection. Altered metabolites, particularly lipid-related metabolites, were identified in infected and mummified larvae, suggesting that lipids are important in O. sinensis -mediated behavioral manipulation of host larvae. Decreased levels of the neurotransmitter acetylcholine were observed in both infected and mummified larvae brains. This suggests that altered or reduced acetylcholine can mediate brain dysfunction and lead to aberrant behavior. These results reveal the critical role of acetylcholine in the mummification process of infected host larvae.