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Context: A disease can be a source of disturbance, causing population declines or extirpations, altering species interactions, and affecting habitat structure. This is particularly relevant for diseases that affect keystone species or ecosystem engineers, leading to potentially cascading effects on ecosystems. Objective: We investigated the invasion of a non-native disease, plague, to a keystone species, prairie dogs, and documented the resulting extent of fragmentation and habitat loss in western grasslands. Specifically, we assessed how the arrival of plague in the Conata Basin, South Dakota, United States, affected the size, shape, and aggregation of prairie dog colonies, an animal species known to be highly susceptible to plague. Methods: Colonies in the prairie dog complex were mapped every 1 to 3 years from 1993 to 2015. Plague was first confirmed in 2008 and we compared prairie dog complex and colony characteristics before and after the arrival of plague. Results: As expected the colony complex and the patches in colonies became smaller and more fragmented after the arrival of plague; the total area of each colony and the mean area per patch within a colony decreased, the number of patches per colony increased, and mean contiguity of each patch decreased, leading to habitat fragmentation. Conclusion: We demonstrate how an emerging infectious disease can act as a source of disturbance to natural systems and lead to potentially permanent alteration of habitat characteristics. While perhaps not traditionally thought of as a source of ecosystem disturbances, in recent years emerging infectious diseases have shown to be able to have large effects on ecosystems if they affect keystone species. [ABSTRACT FROM AUTHOR]