Prevalence and severity of disease of the protozoan parasite Toxoplasma gondii varies geographically in the wide array of hosts T. gondii infects. These facts highlight the need to discover the transmission dynamics and the genetic relationship among strains that are causing the wide spectrum of disease states identified in nature. Specifically, our research addresses the emergence and re-emergence of parasitic zoonotic diseases that have complex life-cycles with multiple routes of transmission that impact people and animals who co-exist in the same ecological niche. We seek discoveries in these areas to support the development of new diagnostic tools, discover fundamental paradigms governing virulence shifts in parasitic protozoa and ultimately develop efficacious anti-protozoal strategies to mitigate the spread of disease. This year we multi-locus genotyped >80 strains isolated from an outbreak of protozoal meningoencephalitis in marine mammals off the coast of Southern California. Collectively, these strains defined a new """"""""wild"""""""" clade of T. gondii organisms that are quite different from archetypal Type I, II and III genotypes commonly infecting people worldwide. We now refer to this new clade of strains as Type X. The frequency of identifying Type X strains has increased substantially over the past 10 years (1990-1995: 10% of otter infections;2000-2005: 75% of otter infections) suggesting that these strains are dynamically emerging in the marine ecosystem. Type X strains have also been identified infecting sylvatic animals in the United States and caused 2 fatal human infections. Ten distinct X genotypes have been resolved genetically, and each possesses a different capacity to cause disease in marine mammals and mice. One Type X genotype is extremely virulent in mice (1 parasite kills a mouse within 8-9 days) whereas other strains are relatively non-pathogenic (LD50>2000 parasites) and readily establish asymptomatic, chronic infections in mice and sea otters. Limited DNA sequencing has so far identified only two alleles at all genetic loci examined that segregate nearly equally among the 10 distinct X types. The most parsimonious explanation to describe the genetic origin and spectrum of virulence associated with these outbreak strains is that they are related progeny from a sexual cross. We are working from the hypothesis that a recent genetic cross generated a subset of Type X progeny that has emerged to cause lethal infections in marine mammals. Reassortment in viruses is a common paradigm for the evolution of new pathogenic """"""""Types"""""""", whether this is common to parasites remains to be established. Discovering whether parasites such Toxoplasma utilize sexual recombination (in effect, a eukaryotic version of reassortment) to evolve new pathotypes capable of occupying new """"""""marine"""""""" niches and cause disease in susceptible animal populations will be an instrumental finding of our work.

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Khan, Asis; Shaik, Jahangheer S; Grigg, Michael E (2018) Genomics and molecular epidemiology of Cryptosporidium species. Acta Trop 184:1-14
Dubey, Jitender P; Trupkiewicz, John G; Verma, Shiv K et al. (2017) Atypical fatal sarcocystosis associated with Sarcocystis neurona in a White-nosed coati (Nasua narica molaris). Vet Parasitol 247:80-84
Iantorno, Stefano A; Durrant, Caroline; Khan, Asis et al. (2017) Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage. MBio 8:
Zhang, Javi; Khan, Asis; Kennard, Andrea et al. (2017) PopNet: A Markov Clustering Approach to Study Population Genetic Structure. Mol Biol Evol 34:1799-1811
Verma, S K; Lindsay, D S; Grigg, M E et al. (2017) Isolation, Culture and Cryopreservation of Sarcocystis species. Curr Protoc Microbiol 45:20D.1.1-20D.1.27
Wilson, Devon J; Orsel, Karin; Waddington, Josh et al. (2016) Neospora caninum is the leading cause of bovine fetal loss in British Columbia, Canada. Vet Parasitol 218:46-51
Barbieri, Michelle M; Kashinsky, Lizabeth; Rotstein, David S et al. (2016) Protozoal-related mortalities in endangered Hawaiian monk seals Neomonachus schauinslandi. Dis Aquat Organ 121:85-95
Chudnovskiy, Aleksey; Mortha, Arthur; Kana, Veronika et al. (2016) Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome. Cell 167:444-456.e14
Lorenzi, Hernan; Khan, Asis; Behnke, Michael S et al. (2016) Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nat Commun 7:10147
Blazejewski, Tomasz; Nursimulu, Nirvana; Pszenny, Viviana et al. (2015) Systems-based analysis of the Sarcocystis neurona genome identifies pathways that contribute to a heteroxenous life cycle. MBio 6:

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