A Single “Kiss” From a Parasite Alters Human Host Cell Metabolism

Thank you. Listen to this article using the player above. ✖

Using the power of optical metabolic imaging (OMI), researchers from the Morgridge Institute for Research have described how the parasite Toxoplasma gondii (T. gondii) “kisses” the surface of host cells before infection and the effect this has on host cell metabolism.

The study was published in the journal mBio.

A deadly kiss

T. gondii is the parasite responsible for toxoplasmosis, a lifelong chronic infection prevalent in approximately one-third of the human population. While the infection poses little harm to healthy individuals, it can cause seizures and neurological defects in immunocompromised people. Infection acquired during pregnancy can be particularly harmful as the parasite can cross the placental barrier and infect the fetus, causing retinal or neurological issues in the developing fetus and, in severe cases, death.

The parasite relies on host cells to provide many of the metabolites it requires to produce energy and replicate. To scavenge these metabolites the parasite remodels the host cell in a process that has, up until now, been understudied.

The researchers hope that by understanding the metabolic relationship between the host cell and the parasite, new treatment and prevention options for T. gondii infections could be uncovered. with no vaccines currently available to prevent infection.

To understand how T. gondii affects the metabolism of host cells the researchers used OMI, a non-invasive technique that enables the observation of real-time changes. This enabled the researchers to monitor metabolism within live cells by detecting fluorescent activity already present in the cells. This method is performed without having to fix or stain samples that would ultimately kill the cells.

The researchers measured the chemical activity of two metabolites – nicotinamide adenine dinucleotide phosphate (NAD(P)H) and flavin adenine dinucleotide (FAD) – to observe changes in redox biology. They found that throughout a 48-hour infection, infected host cells became more oxidized, and NAD(P)H mean lifetime increased. Additionally, they confirmed other metabolic changes in the levels of glucose, lactate and reactive oxygen species (ROS) production.

The study further examined metabolic changes associated with the pre-invasion “kiss and spit” mechanism, where the parasite interacts with the surface of the host cells before mounting a full invasion.

“One cell may be infected while the cells around it are not; it looks like the parasite ‘kisses’ those cells and then injects some proteins – kiss and spit,” said Dr. Gina Gallego-Lopez, assistant scientist at Morgridge and first author of the study. “To our surprise we were able to see similar changes as the full infection. So, it looks like a simple ‘kiss’ from the parasite is enough to induce changes in the host cell.”

Applying non-invasive imaging to other uninvited guests

While there is still more to be uncovered about the infection pathway, the researchers concluded that, “Collectively, our results affirm the value of using autofluorescence lifetime imaging to non-invasively monitor metabolic changes in host cells over the time course of a microbial infection.”

Future studies will include identifying specific genes or proteins involved in these pathways to help design better targets for vaccine development or drug treatment.

Gallego-Lopez hopes to continue studying apicomplexan parasites and apply OMI technology to other parasites such as Cryptosporidium, which is associated with the development of colorectal cancer.

“I want to understand how it’s possible that these parasites induce changes in the host to be able to induce cancer with time,” she said. “I’m using Toxoplasma as a model to understand the changes to later be able to apply in Cryptosporidium. That is my goal.”

Reference: Gallego-López GM, Contreras Guzman E, Desa DE, Knoll LJ, Skala MC. Metabolic changes in Toxoplasma gondii-infected host cells measured by autofluorescence imaging. mBio. 2024;0(0):e00727-24. doi: 10.1128/mbio.00727-24

This article is a rework of a press release. Material has been edited for length and content.