Lessons from Toxoplasma: Host responses that mediate parasite control and the microbial effectors that subvert them

The intracellular parasite Toxoplasma gondii has long provided a tractable experimental system to investigate how the immune system deals with intracellular infections. This review highlights the advances in defining how this organism was first detected and the studies with T. gondii that contribute to our understanding of how the cytokine IFN-γ promotes control of vacuolar pathogens. In addition, the genetic tractability of this eukaryote organism has provided the foundation for studies into the diverse strategies that pathogens use to evade antimicrobial responses and now provides the opportunity to study the basis for latency. Thus, T. gondii remains a clinically relevant organism whose evolving interactions with the host immune system continue to teach lessons broadly relevant to host–pathogen interactions.

CRISPR-Mediated Transcriptional Repression in Toxoplasma gondii

Toxoplasma gondii is a ubiquitous intracellular parasite of humans and animals that causes life-threatening disease in immunocompromised patients, fetal abnormalities when contracted during gestation, and recurrent eye lesions in some patients. Despite its health implications, about half of the Toxoplasma genome still lacks functional annotation.

Unique Tubulin-Based Structures in the Zoonotic Apicomplexan Parasite Cryptosporidium parvum

Cryptosporidium parasites are known to be highly divergent from other apicomplexan species at evolutionary and biological levels. Here we provide evidence showing that the zoonotic Cryptosporidium parvum also differs from other apicomplexans, such as Toxoplasma gondii, by possessing only two tubulin-based filamentous structures, rather than an array of subpellicular microtubules. Using an affinity-purified polyclonal antibody against C. parvum β-tubulin (CpTubB), we observed a long and a short microtubule that are rigid and stable in the sporozoites and restructured during the intracellular parasite development. In asexual development (merogony), the two restructuring microtubules are present in pairs (one pair per nucleus or merozoites). In sexual developmental stages, tubulin-based structures are detectable only in microgametes, but undetectable in macrogametes. These observations indicate that C. parvum parasites use unique microtubule structures that differ from other apicomplexans as part of their cytoskeletal elements.

Role of Imaging in a Case of Toxoplasmosis Presenting as Generalized Lymphadenopathy

Toxoplasmosis is caused by Toxoplasma gondii an obligate protozoan intracellular parasite. The disease has variable prevalence globally and is usually asymptomatic. Pregnant and immunocompromised people are at risk of getting infected. Enlarged lymph nodes are the most frequently observed clinical form of Toxoplasma in humans, mostly affecting posterior cervical nodes. Other organs usually affected are the brain and eyes. We present a case of toxoplasmosis with generalized lymphadenopathy mimicking metastasis in a lady with a previous history of operated pancreatic neoplasm.

the Study of some histopathological changes occurring in white laboratory mice infected with Cutaneous Leishmaniasis in Al – diwaniyah province, Iraq.

Leishmaniasis is caused by an intracellular parasite . It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide, 1.5 to 2 million new cases occur each year .The histological study of the liver tissue of white laboratory mice (Mus musculus) infected with L. major a parasite showed The presence of severe steatosis of hepatocytes Hepatocyte degeneration, And loss of the radial arrangement of hepatocytes, With heavy infiltration in inflammatory cells, especially phagocytes( Macrophage) with Hyperplasia and congestion of the bile duct . As for histological sections of skin lesions taken from ear , Foot , tail ، were showed epidermal ulcerative , Accompanied by severe leaching of the dermis layer neutrophil ,polymorph lymphocytes ، with hemorrhage of ​​the dermis, with necrosis of the epidermal cells of all skin lesions in the ear, foot and tail.

In Vitro Genotoxic Effects of Sarcocystis gigantea Cystizoites Acetone Powder Extract on Sheep Lymphocytes

The toxin of the protozoan intracellular parasite of sheep Sarcocystis gigantea is associated with many clinical and pathological signs. The aim of the study was to investigate In Vitro various chromosomal aberrations due to sarcocystosis infection. Macrocysts of Sarcocystis gigantea were isolated from local karadi sheep, homogenized with glass Dounce homogenizer; acetone powder was prepared from it and used in various concentration to investigate the chromosomal aberration in vitro against sheep lymphocytes. The direct effects of parasite cystizoites acetone powder revealed various genotoxicity effects. These effects included chromosomal aberration (Isogap, Breaks and Dicentrics) and chromatids aberration (Gap and Deletion). It had also an effect on the mitotic index of the lymphocyte cells division. These genotoxicities were studied for the first time with in vitro technique using sheep lymphocytes. These results reflected that Sarcocystis gigantean parasite could cause structural and internal aberration in the chromosomes of their hosts.

Single-cell sequencing of the small and AT-skewed genome of malaria parasites

Single-cell genomics is a rapidly advancing field; however, most techniques are designed for mammalian cells. We present a single-cell sequencing pipeline for an intracellular parasite, Plasmodium falciparum, with a small genome of extreme base content. Through optimization of a quasi-linear amplification method, we target the parasite genome over contaminants and generate coverage levels allowing detection of minor genetic variants. This work, as well as efforts that build on these findings, will enable detection of parasite heterogeneity contributing to P. falciparum adaptation. Furthermore, this study provides a framework for optimizing single-cell amplification and variant analysis in challenging genomes.

Chlamydia trachomatis TmeA Directly Activates N-WASP To Promote Actin Polymerization and Functions Synergistically with TarP during Invasion

ABSTRACT Chlamydia trachomatis is a medically significant human pathogen and is an epithelial-tropic obligate intracellular parasite. Invasion of nonprofessional phagocytes represents a crucial step in the infection process and has likely promoted the evolution of a redundant mechanism and routes of entry. Like many other viral and invasive bacterial pathogens, manipulation of the host cell cytoskeleton represents a focal point in Chlamydia entry. The advent of genetic techniques in C. trachomatis, such as creation of complete gene deletions via fluorescence-reported allelic exchange mutagenesis (FRAEM), is providing important tools to unravel the contributions of bacterial factors in these complex pathways. The type III secretion chaperone Slc1 directs delivery of at least four effectors during the invasion process. Two of these, TarP and TmeA, have been associated with manipulation of actin networks and are essential for normal levels of invasion. The functions of TarP are well established, whereas TmeA is less well characterized. We leverage chlamydial genetics and proximity labeling here to provide evidence that TmeA directly targets host N-WASP to promote Arp2/3-dependent actin polymerization. Our work also shows that TmeA and TarP influence separate, yet synergistic pathways to accomplish chlamydial entry. These data further support an appreciation that a pathogen, confined by a reductionist genome, retains the ability to commit considerable resources to accomplish bottle-neck steps during the infection process. IMPORTANCE The increasing genetic tractability of Chlamydia trachomatis is accelerating the ability to characterize the unique infection biology of this obligate intracellular parasite. These efforts are leading to a greater understanding of the molecular events associated with key virulence requirements. Manipulation of the host actin cytoskeleton plays a pivotal role throughout Chlamydia infection, yet a thorough understanding of the molecular mechanisms initiating and orchestrating actin rearrangements has lagged. Our work highlights the application of genetic manipulation to address open questions regarding chlamydial invasion, a process essential to survival. We provide definitive insight regarding the role of the type III secreted effector TmeA and how that activity relates to another prominent effector, TarP. In addition, our data implicate at least one source that contributes to the functional divergence of entry mechanisms among chlamydial species.