MIC17A is a novel diagnostic marker for feline toxoplasmosis

Abstract

Toxoplasma gondii is a widespread parasitic pathogen that infect humans and all warm-blooded animals, causing abortion and stillbirth in pregnant women and animals, as well as life threatening toxoplasmosis in immune compromised individuals. Felines are the only definitive hosts of Toxoplasma and oocysts shed by infected felines are the major source of infection for humans and other animals. Given the critical role of felines for T. gondii transmission, control of feline toxoplasmosis has significant impacts on reducing the overall prevalence of animal and human toxoplasmosis. However, reliable diagnosis of feline toxoplasmosis is still challenging. In this study, we found that the putative micronemal protein 17A (MIC17A) that was abundantly expressed in Toxoplasma merozoites is a good diagnostic marker for serological diagnosis of Toxoplasma infection in felines. T. gondii encodes four paralogs of MIC17A in total and the expression of three of them is drastically upregulated in merozoites than in tachyzoites. In contrast, when proteins like GRA1 and MIC3 that are more abundantly expressed in tachyzoites than in merozoites were used as diagnostic antigens to test feline toxoplasmosis, they reacted with Toxoplasma specific IgG antibodies poorly. Taken together, these results suggest that merozoite antigens are better suited for the diagnosis of feline toxoplasmosis than antigens that are highly expressed at tachyzoite or bradyzoite stages.

TgLaforin, a glucan phosphatase, reveals the dynamic role of storage polysaccharides inToxoplasma gondiitachyzoites and bradyzoites

“…The loss of other glucan phosphatases such as SEX4 in A. thaliana and laforin in mammals is accompanied by excessive accumulation of aberrant starch and hyperphosphorylated glycogen in plants and animals (33,34,37,38,78). Surprisingly, given these penalties in other systems, ∆TgLaf tachyzoites exhibited no gross morphological changes in glucan content, consistent with a recent study in which TgGWD was knocked out (32). These observations contrasts with other KO studies of glucan pathway associated proteins such as CDPK2, glycogen phosphorylase, the PP2A holoenzyme, and α-amylase which all reported exaggerated glucan accumulation in tachyzoites (14,39,41,42,56).…”

“…Reversible glucan phosphorylation facilitates the breakdown of such glucan polymers by disrupting the crystalline helices on the glucan surface (77). T. gondii encodes the capacity for reversible glucan phosphorylation (30,32,43,44).…”

“…Glucose-releasing enzymes (amylases) then degrade starch until the glucan-bound phosphate becomes a steric hindrance, at which point a glucan phosphatase is needed to remove the phosphate and reset the cycle (26)(27)(28)(29). T. gondii encodes all the activities needed for glucan degradation and reversible glucan phosphorylation including the glucan phosphatase, TgLaforin (TGME49_205290) (30), and glucan dikinase, T. gondii GWD (TgGWD; TGME49_214260) (31,32) .…”

Advances and Challenges in Diagnostics of Toxoplasmosis in HIV-Infected Patients

“…Toxoplasma gondii is an obligate intracellular protozoan parasite of 300 species of mammals and more than 30 species of birds [ 1 ]. The parasite occurs worldwide, infecting one-third of the population worldwide [ 2 , 3 , 4 ]. T. gondii is a pathogen of relevant medical and veterinary significance [ 3 ].…”

“…The parasite occurs worldwide, infecting one-third of the population worldwide [ 2 , 3 , 4 ]. T. gondii is a pathogen of relevant medical and veterinary significance [ 3 ]. It is a unique parasite whose interesting development cycle makes it possible to infect humans in various ways, mainly by consuming raw meat containing tissue cysts and accidentally ingesting oocysts in food, water, or soil contaminated with cat feces.…”