Virulence factors of Toxoplasma gondii

Dubremetz, Jean François; Lebrun, Maryse

doi:10.1016/j.micinf.2012.09.005

Cited by 57 publications

(50 citation statements)

References 65 publications

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“…Type II and III strains are only moderately virulent under identical experimental conditions [25]. These differences observed in animals have a genetic basis and are linked to certain gene loci coding for rhoptry proteins (ROP18, ROP5 and ROP16) [25,26]. …”

Section: Parasite-related Factors: Do T Gondii Strains Influence CLImentioning

confidence: 99%

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Pleyer

Schlüter

Mänz³

2014

Ophthalmic Res

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Toxoplasma gondii is an extremely successful opportunistic parasite which infects approximately one third of the human population worldwide. The impact of this parasite on human health becomes particularly manifest in congenital damage with infection and subsequent inflammation of neuronal tissues including the retina. Although advances in our understanding could be achieved in ocular toxoplasmosis, large gaps still exist on factors influencing the epidemiology and pathophysiology of this potentially blinding disease. We are only at the beginning of understanding the complex biology of this parasite and its mechanisms of invasion, virulence and interaction with the host's immune response. Since it is a preventable cause of blindness, it is necessary to assess factors that have the potential to control this disease in the future. This mini review will focus on recent advances in postnatal acquired ocular infection and the factors that may influence its prevalence and functional outcome.

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Section: Parasite-related Factors: Do T Gondii Strains Influence CLImentioning

confidence: 99%

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Pleyer

Schlüter

Mänz³

2014

Ophthalmic Res

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“…In addition, we discuss how parasites interact with neighboring host cells and propose how this may contribute to establishing a permissive microenvironment to improve its overall success. In particular, we focus on those processes that are essential for the growth of all parasite strains and we refer readers to recent reviews that highlight how polymorphic parasite molecules contribute to Toxoplasma virulence (3)(4)(5).…”

mentioning

confidence: 99%

Toxoplasma gondii Development of Its Replicative Niche: in Its Host Cell and Beyond

Blader

Koshy

2014

Eukaryot Cell

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b Intracellular pathogens can replicate efficiently only after they manipulate and modify their host cells to create an environment conducive to replication. While diverse cellular pathways are targeted by different pathogens, metabolism, membrane and cytoskeletal architecture formation, and cell death are the three primary cellular processes that are modified by infections. Toxoplasma gondii is an obligate intracellular protozoan that infects ϳ30% of the world's population and causes severe and lifethreatening disease in developing fetuses, in immune-comprised patients, and in certain otherwise healthy individuals who are primarily found in South America. The high prevalence of Toxoplasma in humans is in large part a result of its ability to modulate these three host cell processes. Here, we highlight recent work defining the mechanisms by which Toxoplasma interacts with these processes. In addition, we hypothesize why some processes are modified not only in the infected host cell but also in neighboring uninfected cells.T oxoplasma gondii is a protozoan, obligate intracellular parasite that is considered one of the world's most successful pathogens (1). Multiple factors contribute to this success, including a complex life cycle in which the parasite can be transmitted by both vertical and horizontal means, efficient propagation within both its primary (felines) and intermediate hosts, extensive mechanisms to evade and disarm host immunity, an ability to form chronic lifelong infections in intermediate hosts, and a wide host tropism in which the parasite can infect most nucleated cells of warm-blooded animals (2). Central to most of these factors is that Toxoplasma has developed the means to replicate efficiently within the hostile intracellular environment of its host cell. In this review, we highlight recent data that have shed light on how parasite growth is achieved by the parasite interacting with its host cell to manipulate host signaling cascades, transcription, cell survival pathways, and membrane transport. In addition, we discuss how parasites interact with neighboring host cells and propose how this may contribute to establishing a permissive microenvironment to improve its overall success. In particular, we focus on those processes that are essential for the growth of all parasite strains and we refer readers to recent reviews that highlight how polymorphic parasite molecules contribute to Toxoplasma virulence (3-5). NUTRIENT ACQUISITIONAs an obligate intracellular parasite that resides within a nonfusogenic vacuole, Toxoplasma must satisfy its nutritional needs by scavenging essential nutrients from its host cell. These nutrients include carbon sources (glucose and glutamine) to fuel its energy demands, specific amino acids, lipids, and other nutrients. Below, we discuss each of these and highlight pathways and processes that are unique to the parasite that could serve as novel drug targets (Fig. 1). GLUCOSE AND GLUTAMINE POWER THE PARASITEToxoplasma expresses a full complement of glycolytic and tr...

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“…Rhoptry neck proteins (RONs), ROPs and dense granule proteins (GRAs) were related to invasion, proliferation, and formation of PV (Sinai and Joiner, 2001; Dubremetz and Lebrun, 2012; Nolan et al, 2015). To detect whether these genes were affected by NcROP5 , we selected RON2, RON4, ROP4, ROP7, ROP16, ROP17, GRA2, GRA6 , and GRA7 genes to evaluate their mRNA expression.…”

Section: Resultsmentioning

confidence: 99%

Rhoptry protein 5 (ROP5) Is a Key Virulence Factor in Neospora caninum

Liu

et al. 2017

Front. Microbiol.

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Neospora caninum, of the Apicomplexa phylum, is a common cause of abortions in cattle and nervous system dysfunction in dogs. Rhoptry proteins of Apicomplexa play an important role in virulence. The objectives of this study were to study functions of NcROP5 in N. caninum by deleting the NcROP5 gene from the wild Nc-1 strain. We selected NcROP5 in ToxoDB and successfully constructed an NcROP5 gene-deleted vector, pTCR-NcROP5-CD KO. Then we screened the NcROP5 knockout strains (ΔNcROP5) at the gene, protein and transcription levels. Plaque assay, host cell invasion assay and intracellular proliferation test showed that the ΔNcROP5 strain had less plaque space, weakened invasion capacity and slower intracellular growth. Animal testing showed significantly lower cerebral load of ΔNcROP5 than the load of the Nc-1 strain, as well as a loss of virulence for the ΔNcROP5 strains. Phenotypic analyses using the label-free LC-MS/MS assay-based proteomic method and KEGG pathway enrichment analysis showed a reduction of NcGRA7 transcription and altered expression of multiple proteins including the apicomplexan family of binding proteins. The present study indicated that ROP5 is a key virulence factor in N. caninum in mice. The proteomic profiling of Nc-1 and ΔNcROP5 provided some data on differential proteins. These data provide a foundation for future research of protein functions in N. caninum.

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Virulence factors of Toxoplasma gondii

Cited by 57 publications

References 65 publications

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Toxoplasma gondii Development of Its Replicative Niche: in Its Host Cell and Beyond

Rhoptry protein 5 (ROP5) Is a Key Virulence Factor in Neospora caninum

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