Human impact on the diversity and virulence of the ubiquitous zoonotic parasite 2 Toxoplasma gondii

Authors: KEATS, SHWAB - University Of Tennessee; SARAF, POOJA - University Of Tennessee; ZHU, XING-QUAN - Lanzhou Institute Of Veterinary Research; ZHOU, DONG-HUI - Lanzhou Institute Of Veterinary Research; MCFERRIN, BRENT - University Of Tennessee; AJZENBERG, DANIEL - Laboratoire Parasitologie-Mycologie; SCHARES, GEREON - Federal Research Institute; HAMMOND-ARYEE, KENNETH - Stellenbosch University; HIGGINS, STEVE - University Of Tennessee; GERHOLD, RICHARD - University Of Tennessee; Rosenthal, Benjamin; ZHAO, XIAOPENG - University Of Tennessee; Dubey, Jitender; SU, CHUNLEI - University Of Tennessee

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/23/2018
Publication Date: 7/2/2018
Citation: Keats, S., Saraf, P., Zhu, X., Zhou, D., Mcferrin, B., Ajzenberg, D., Schares, G., Hammond-Aryee, K., Higgins, S., Gerhold, R., Rosenthal, B.M., Zhao, X., Dubey, J.P., Su, C. 2018. Human impact on the diversity and virulence of the ubiquitous zoonotic parasite 2 Toxoplasma gondii. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1722202115.
DOI: https://doi.org/10.1073/pnas.1722202115

Interpretive Summary: Most emerging infectious diseases in humans are zoonoses. Among these pathogens, the zoonotic protozoan parasite T. gondii is perhaps the most ubiquitous, having been identified in the tissues of a variety of animal hosts, including both mammalian and avian species. Toxoplasma gondii is estimated to chronically infect one third of the world’s human population, causing ocular toxoplasmosis in immunocompetent individuals and often-fatal encephalitis in the immunocompromised, as well as birth defects and mortality following vertical transmission to developing fetuses. Globally, this parasite has distinct population structures for each major geographic region examined, with striking contrast between the highly diverse, epidemic structure of the Central/South American region and the more clonal populations found in all other areas, wherein North America, Europe and north Africa, and east Asia are each dominated by particular clonal genotypes. It is generally agreed that our behavior can influence our exposure to such pathogens, but little is known regarding our role in shaping evolution in such pathogens. Such understanding would aid in their control, to the benefit of public health. The results of this investigation indicate that expansion of agriculture influenced not only the biogeography but also the virulence of Toxoplasma gondii. By linking landscape ecology to parasite virulence, our framework contributes a fundamentally novel perspective on the ecology and evolution of infectious disease. These results will be of interest to parasitologists, biologists, and microbiologists.

Technical Abstract: The majority of emerging infectious diseases in humans are zoonoses. Understanding factors that influence the emergence and transmission of zoonoses is pivotal for their prevention and control. Toxoplasma gondii is one of the most widespread zoonotic pathogens known today. Whereas only a few genotypes of T. gondii dominate in the northern hemisphere, many genotypes co-exist in South America. Furthermore, T. gondii strains from South America are more likely to be virulent than those from the northern hemisphere. However, it is not clear what factor(s) shaped modern-day genetic diversity and virulence of T. gondii. Here our analysis suggests that the rise and expansion of farming in the past 11,000 years established the domestic cat-mouse transmission cycle for T. gondii, which has undoubtedly played a significant role in the selection of certain linages of T. gondii. Our mathematical simulations showed that within the domestic transmission cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive advantage and eventually become dominant due to a balance between lower host mortality and the ability to superinfect mice previously infected with a less virulent T. gondii strain. Our analysis of the global type II lineage of T. gondii suggests its Old World origin but recent expansion in North America, which is likely the consequence of global human migration and trading. These results have significant implications concerning transmission and evolution of 64 zoonotic pathogens in the rapidly expanding anthropized environment demanded by rapid growth of the human population and intensive international trading at present and in the future.