Toxoplasma Research and Training Laboratory at the University of Tennessee

- Molecular Epidemiology and Population Genetics of Toxoplasma gondii
- Principle investigator: Dr. Chunlei Su


Toxoplasma gondii

Toxoplasma gondii is a single-cell parasite that infects mammals and birds. On average, one third of human population is chronically infected. Infection of T. gondii can cause congenital, ocular or acute disseminated diseases in healthy individuals, and severe encephalitis in immunocompromised individuals such as AIDS patients.

Toxoplasma gondii has a complex life cycle. Felids (domestic and wild cats) are the only known definitive hosts, in which the parasite can reproduce sexually to generate hundreds of millions of oocysts that are shed into the environment in cat feces. Within a few days, oocysts in the environment mature to produce infectious parasites called sporozoites. All warm-blooded vertebrates (mammals and birds) can serve as intermediate hosts, which acquire infection through ingesting soil, water, or plants contaminated with oocysts. Parasites in an intermediate host undergo asexual replication. In about a week, the parasites may switch to a slow-growing phase (bradyzoites), producing relatively quiescent tissue cysts, which are often localized in brain and muscle tissues. Transmission also occurs through cannibalism, predation and scavenging among intermediate hosts. Humans become infected with T. gondii congenitally or by ingestion of either oocysts in contaminated food and water, or tissue cysts in undercooked meat of infected animals. Upon ingestion of oocysts or tissue cysts, the parasites are released, penetrate the intestinal cells, and replicate rapidly inside host cells. Rapid replication is responsible for systemic dissemination of the parasite, and most of the pathology associated with acute toxoplasmosis. Host immune response eventually eliminates fast-replicating parasites but a population of parasites switch to slow-replicating stage that encyst and establish chronic infection primarily in the brain and muscle tissue. Severe disease results in immune suppressed individuals (e.g., AIDS patients) due to reactivation of parasite replication in the absence of effective immune control. Currently there are no therapeutics capable of eliminating the chronic stage of T. gondii infection.

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Research Interests

Our laboratory is interested in studying molecular epidemiology, population genetics and evolution of T. gondii. Our goal is to reveal major reservoirs and transmission modes through which the parasite spreads among different hosts, particularly in humans. To reach this goal, we first developed a simple and cost-effective molecular method to identify T. gondii isolates (Su et al., Int. J. Parasitol. 2006, 36:841-848; Su et al., Parasitology, 2010; 137:1-11), and applied the method to thousands of samples collected worldwide. Our studies revealed global patterns of genetic diversity of T. gondii (Su et al., PNAS, 2012, 109:5844-5849; Shwab et al., Parasitology, 2014, 141:453-461). Our analysis revealed distinct distribution patterns of T. gondii types for each major geographic region examined, with striking contrast between the highly diverse of the Central/South American region and the more clonal populations found in all other areas. North America, Europe, North Africa, and East Asia are each dominated by particular clonal types. Interestingly, T. gondii strains from Central/South America were more likely to be virulent. These results set the stage for future studies aimed to identify the factors that may drive population diversity and the factors responsible for rapid expansion of this parasite on our planet. To reach this goal, we would like to isolate T. gondii from domestic and feral cats, humans, and wild animals all over the world. We will determine virulence of these parasites, generate whole genome sequences for genetic analysis. Given the scale of such study, we would like to expand collaborations with other research laboratories around the world. We have established a complete set of research protocols and have been providing in-house training for visiting scholars worldwide in the past decade. If you are interested in collaboration and get trained, please contact our lab at csu1@utk.edu.

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List of ToxoDB PCR-RFLP Genotypes


Collaboration and Training

For zoos and animal health research groups that are interested in studying epidemiology of T. gondii, we are looking forward to collaboration and can offer essential training. Individuals who have pets that are diagnosed with acute toxoplasmosis are welcome to contact us and then have your veterinarians send samples (blood and tissues) for further analysis.

To facilitate epidemiological research of T. gondii infection, we have developed a complex toolkit that can conduct the following studies:

1. Screen serum or plasma samples to identify T. gondii infection. This is achieved by the modified agglutination test (MAT) which detects antibodies to T. gondii in the blood.

2. Isolate T. gondii from human and animal tissues by bioassay. This will allow us to obtain highly purified T. gondii parasites for molecular identification and whole-genome sequence analysis.

3. Identify T. gondii by the molecular method multilocus genotyping. For this analysis, we amplify 10 DNA fragments in the genome of T. gondii by polymerase chain reaction (PCR), then reveal DNA sequence difference among T. gondii samples by restriction fragment length polymorphism (RFLP).

In addition, we have capacity to determine drug sensitivity of T. gondii strains. Drug sensitivity test of T. gondii strains is conducted in vitro using cell culture. This is to obtain preliminary information regarding if a drug has the potential to be used to treat T. gondii infection.


Reagents

If you need MAT antigens for research, please visit website UT Research Foundation. For detailed information of the antigens, check the link here.


Publications

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Contact information

Dr. Chunlei Su
F409, WLS
Department of Microbiology
University of Tennessee
Knoxville, TN 37996
Email: csu1@utk.edu