Undead Arthropods: The Fungal Delivery Service

Somewhere in southeastern North America, there is a carpenter ant currently, against its own will, biting on a twig so hard that it dies, remaining fixated in that position long after its death. The culprit is no other than Ophiocordyceps kimflemingiae (Ballesteros-Aguirre et. al, 2025).

Once a spore is inside the body of an ant, it begins to siphon nutrients out of the ant’s body, eventually penetrating the ants muscles. However, they do not begin to break down the ant’s body until after death, allowing the ant to continue consuming nutrients until it dies.

Figure 1: Ophiocordyceps kimflemingiae cells form expansive networks woven around infected ant muscle, connecting via tubes as shown by the arrows (Mangold et. al 2019).

To ensure that the ant’s muscles are strong enough to enter its death grip, the fungus coerces the muscles into a state of constant hypercontraction to compensate for their atrophy. Eventually, the ant, being puppeteered by the fungal network inside of it, climbs a tree to reach proper conditions, and bites down on a twig with the last of its strength, dying in the process. The fungus then begins to extend a stalk from the head of the ant’s corpse, and will eventually release pores to disperse and infect new victims (Mangold et. al 2019).

However, the dead ant is now prone to other microbes colonizing its corpse and stealing the nutrients the stalk needs to grow. Thus, many species of Ophiocordyceps defend their property by means of antimicrobials.

One of these antimicrobials is a derivative of 1,4-naphthoquinone. 1,4-naphthoquinone functions as an antimicrobial by inducing reactive oxygen species production, resulting in the damaging of cells (Liu et al. 2022).

Figure 2: Juglone, a type of 1,4-naphthoquinone prompts the production of reactive oxygen species in cells (Liu et al. 2022).

Reactive oxygen species (ROS) are oxidizing agents, which readily accept electrons from various molecules in the cell, such as lipids, proteins, and DNA. When an ROS reacts with an unsaturated lipid chain such as one in the cell membrane, a series of reactions forms a peroxyl radical, which can react with adjacent unsaturated lipid chains, resulting in a destructive chain reaction which can severely impair the cell membrane.

Due to the varied nature of proteins and amino acids, effects of ROS vary depending on the molecule. Upon reacting with an ROS, amino acids may be oxidized, crucial peptide bonds may be broken, and different protein chains as a whole may cluster together.

When an ROS comes into contact with DNA, it is able to react with deoxyribose, altering the critical structure of the chain, as well as the nucleotides themselves, resulting in mutations that may severely inhibit a cell’s ability to survive and reproduce (Juan et al. 2021).

Figure 3: DNA damage caused by ROS (Juan et al. 2021).

Though 1,4-naphthoquinones are not the only way that Ophiocordyceps fungi defend their resources, they are prominent as they are currently being studied for potential uses as antibacterial compounds in humans. Plus, Ophiocordyceps fungi are the basis for the critically acclaimed The Last of Us franchise. They are truly a gift that keeps on giving!

References

Ballesteros-Aguirre, C.E., T. Sanjuan, V. Ramírez-Cruz, A.R. Villalobos-Arámbula, M. Vásquez-Bolaños, and L. Guzmán-Dávalos. “Zombie-Ant Fungi from Western Mexico: Six New Species in the Ophiocordyceps Unilateralis Complex (Hypocreales: Ascomycota) and a New Host Association with Cephalotes Ants.” Persoonia – Molecular Phylogeny and Evolution of Fungi 55, no. 1 (December 31, 2025): 203–38. https://doi.org/10.3114/persoonia.2025.55.06.

Juan, Celia Andrés, José Manuel Pérez de la Lastra, Francisco J. Plou, and Eduardo Pérez-Lebeña. “The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies.” International Journal of Molecular Sciences 22, no. 9 (April 28, 2021): 4642. https://doi.org/10.3390/ijms22094642.

Kittakoop, Prasat, Juntira Punya, Palangpon Kongsaeree, Yuwapin Lertwerawat, Amnuay Jintasirikul, Morakot Tanticharoen, and Yodhathai Thebtaranonth. “Bioactive Naphthoquinones from Cordyceps Unilateralis.” Phytochemistry 52, no. 3 (October 1999): 453–57. https://doi.org/10.1016/s0031-9422(99)00272-1.

Liu, Zhizhuo, Zhemin Shen, Shouyan Xiang, Yang Sun, Jiahua Cui, and Jinping Jia. “Evaluation of 1,4-Naphthoquinone Derivatives as Antibacterial Agents: Activity and Mechanistic Studies.” Frontiers of Environmental Science & Engineering 17, no. 3 (October 20, 2022). https://doi.org/10.1007/s11783-023-1631-2.

Lu, Yingling, Dexiang Tang, Zuoheng Liu, Jing Zhao, Yue Chen, Jinmei Ma, Lijun Luo, and Hong Yu. “Genomic Comparative Analysis of Ophiocordyceps Unilateralis Sensu Lato.” Frontiers in Microbiology 15 (April 15, 2024). https://doi.org/10.3389/fmicb.2024.1293077.

Mangold, Colleen A., Melissa J. Ishler, Raquel G. Loreto, Missy L. Hazen, and David P. Hughes. “Zombie Ant Death Grip Due to Hypercontracted Mandibular Muscles.” Journal of Experimental Biology 222, no. 14 (July 15, 2019). https://doi.org/10.1242/jeb.200683.

Wang, Wenting, Bohan Cheng, Haotian Wu, Yuhua Shi, Lan Wu, Qinggang Yin, Mengyue Wang, et al. “Composition, Biosynthesis and Pharmacological Activities of Chemical Constituents of Ophiocordyceps Sinensis: A Review.” Medicinal Plant Biology 4, no. 1 (July 25, 2025). https://doi.org/10.48130/mpb-0025-0024.