scholarly journals Pyruvate Homeostasis as a Determinant of Parasite Growth and Metabolic Plasticity inToxoplasma gondii

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Ningbo Xia ◽  
Shu Ye ◽  
Xiaohan Liang ◽  
Pu Chen ◽  
Yanqin Zhou ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Carbon Metabolism ◽  
Critical Role ◽  
Carbon Sources ◽  
Parasite Growth ◽  
Lytic Cycle ◽  
Current Understanding ◽  
Metabolic Flexibility ◽  
Lactate Dehydrogenase Activity ◽  
Content Type

ABSTRACTToxoplasma gondiiis a widespread intracellular pathogen infecting humans and a variety of animals. Previous studies have shown thatToxoplasmauses glucose and glutamine as the main carbon sources to support asexual reproduction, but neither nutrient is essential. Such metabolic flexibility may allow it to survive within diverse host cell types. Here, by focusing on the glycolytic enzyme pyruvate kinase (PYK) that converts phosphoenolpyruvate (PEP) into pyruvate, we found thatToxoplasmacan also utilize lactate and alanine. We show that catabolism of all indicated carbon sources converges at pyruvate, and maintaining a constant pyruvate supply is critical to parasite growth.Toxoplasmaexpresses two PYKs: PYK1 in the cytosol and PYK2 in the apicoplast (a chloroplast relict). Genetic deletion ofPYK2did not noticeably affect parasite growth and virulence, which contrasts with the current model of carbon metabolism in the apicoplast. On the other hand,PYK1was refractory to disruption. Conditional depletion of PYK1 resulted in global alteration of carbon metabolism, amylopectin accumulation, and reduced cellular ATP, leading to severe growth impairment. Notably, the attenuated growth of the PYK1-depleted mutant was partially rescued by lactate or alanine supplementation, and rescue by lactate required lactate dehydrogenase activity to convert it to pyruvate. Moreover, depletion of PYK1 in conjunction with PYK2 ablation led to accentuated loss of apicoplasts and complete growth arrest. Together, our results underline a critical role of pyruvate homeostasis in determining the metabolic flexibility and apicoplast maintenance, and they significantly extend our current understanding of carbon metabolism inT. gondii.IMPORTANCEToxoplasma gondiiinfects almost all warm-blooded animals, and metabolic flexibility is deemed critical for its successful parasitism in diverse hosts. Glucose and glutamine are the major carbon sources to support parasite growth. In this study, we found thatToxoplasmais also competent in utilizing lactate and alanine and, thus, exhibits exceptional metabolic versatility. Notably, all these nutrients need to be converted to pyruvate to fuel the lytic cycle, and achieving a continued pyruvate supply is vital to parasite survival and metabolic flexibility. Although pyruvate can be generated by two distinct pyruvate kinases, located in cytosol and apicoplast, respectively, the cytosolic enzyme is the main source of subcellular pyruvate, and cooperative usage of pyruvate among multiple organelles is critical for parasite growth and virulence. These findings expand our current understanding of carbon metabolism inToxoplasma gondiiand related parasites while providing a basis for designing novel antiparasitic interventions.

scholarly journals Two Phosphoglucomutase Paralogs Facilitate Ionophore-Triggered Secretion of the Toxoplasma Micronemes

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Sudeshna Saha ◽  
Bradley I. Coleman ◽  
Rashmi Dubey ◽  
Ira J. Blader ◽  
Marc-Jan Gubbels
Keyword(s):  
Toxoplasma Gondii ◽  
Phosphatidic Acid ◽  
Host Cell ◽  
Lytic Cycle ◽  
Ionophore A23187 ◽  
Host Cell Invasion ◽  
Content Type ◽  
Apicomplexan Parasites ◽  
Genetic Deletion

ABSTRACT Ca2+-dependent exocytosis is essential for the life cycle of apicomplexan parasites. Toxoplasma gondii harbors a phosphoglucomutase (PGM) ortholog, PRP1, previously associated with Ca2+-dependent microneme secretion. Here it is shown that genetic deletion of either PRP1, its PGM2 ortholog, or both genes is dispensable for the parasite’s lytic cycle, including host cell egress and invasion. Depletion of the proteins abrogated high Ca2+-mediated microneme secretion induced by the ionophore A23187; however, the constitutive and phosphatidic acid-mediated release remained unaffected. Secretion mediated by the former pathway is not essential for tachyzoite survival or acute in vivo infection in the mice. Paralogs of the widely prevalent phosphoglucomutase (PGM) protein called parafusin function in calcium (Ca2+)-mediated exocytosis across eukaryotes. In Toxoplasma gondii, the parafusin-related protein 1 (PRP1) has been associated with Ca2+-dependent microneme organelle secretion required for essential processes like host cell invasion and egress. Using reverse genetics, we observed PRP1 to be dispensable for completion of the lytic cycle, including host cell invasion and egress by the parasite. However, the absence of the gene affected increased microneme release triggered by A23187, a Ca2+ ionophore used to raise the cytoplasmic Ca2+ concentration mimicking the physiological role of Ca2+ during invasion and egress. The basal levels of constitutive microneme release in extracellular parasites and phosphatidic acid-triggered microneme secretion were unaffected in the mutant. The phenotype of the deletion mutant of the second PGM-encoding gene in Toxoplasma, PGM2, was similar to the phenotype of the PRP1 deletion mutant. Furthermore, the ability of the tachyzoites to induce acute infection in the mice remained normal in the absence of both PGM paralogs. Our data thus reveal that the microneme secretion upon high Ca2+ flux is facilitated by the Toxoplasma PGM paralogs, PRP1 and PGM2. However, this protein-mediated release is neither essential for lytic cycle completion nor for acute virulence of the parasite. IMPORTANCE Ca2+-dependent exocytosis is essential for the life cycle of apicomplexan parasites. Toxoplasma gondii harbors a phosphoglucomutase (PGM) ortholog, PRP1, previously associated with Ca2+-dependent microneme secretion. Here it is shown that genetic deletion of either PRP1, its PGM2 ortholog, or both genes is dispensable for the parasite’s lytic cycle, including host cell egress and invasion. Depletion of the proteins abrogated high Ca2+-mediated microneme secretion induced by the ionophore A23187; however, the constitutive and phosphatidic acid-mediated release remained unaffected. Secretion mediated by the former pathway is not essential for tachyzoite survival or acute in vivo infection in the mice.

scholarly journals The Catabolite Repressor/Activator Cra Is a Bridge Connecting Carbon Metabolism and Host Colonization in the Plant Drought Resistance-Promoting Bacterium Pantoea alhagi LTYR-11Z

2018 ◽  
Vol 84 (13) ◽  
Author(s):  
Lei Zhang ◽  
Muhang Li ◽  
Qiqi Li ◽  
Chaoqiong Chen ◽  
Meng Qu ◽  
...  
Keyword(s):  
Carbon Source ◽  
Carbon Metabolism ◽  
Carbon Sources ◽  
Endophytic Bacterium ◽  
Bacterial Attachment ◽  
Gene Encoding ◽  
Wheat Roots ◽  
Host Colonization ◽  
Content Type

ABSTRACT Efficient root colonization is a prerequisite for application of plant growth-promoting (PGP) bacteria in improving health and yield of agricultural crops. We have recently identified an endophytic bacterium, Pantoea alhagi LTYR-11Z, with multiple PGP properties that effectively colonizes the root system of wheat and improves its growth and drought tolerance. To identify novel regulatory genes required for wheat colonization, we screened an LTYR-11Z transposon (Tn) insertion library and found cra to be a colonization-related gene. By using transcriptome (RNA-seq) analysis, we found that transcriptional levels of an eps operon, the ydiV gene encoding an anti-FlhD 4 C 2 factor, and the yedQ gene encoding an enzyme for synthesis of cyclic dimeric GMP (c-di-GMP) were significantly downregulated in the Δ cra mutant. Further studies demonstrated that Cra directly binds to the promoters of the eps operon, ydiV , and yedQ and activates their expression, thus inhibiting motility and promoting exopolysaccharide (EPS) production and biofilm formation. Consistent with previous findings that Cra plays a role in transcriptional regulation in response to carbon source availability, the activating effects of Cra were much more pronounced when LTYR-11Z was grown within a gluconeogenic environment than when it was grown within a glycolytic environment. We further demonstrate that the ability of LTYR-11Z to colonize wheat roots is modulated by the availability of carbon sources. Altogether, these results uncover a novel strategy utilized by LTYR-11Z to achieve host colonization in response to carbon nutrition in the environment, in which Cra bridges a connection between carbon metabolism and colonization capacity of LTYR-11Z. IMPORTANCE Rapid and appropriate response to environmental signals is crucial for bacteria to adapt to competitive environments and to establish interactions with their hosts. Efficient colonization and persistence within the host are controlled by various regulatory factors that respond to specific environmental cues. The most common is nutrient availability. In this work, we unraveled the pivotal role of Cra in regulation of colonization ability of Pantoea alhagi LTYR-11Z in response to carbon source availability. Moreover, we identified three novel members of the Cra regulon involved in EPS synthesis, regulation of flagellar biosynthesis, and synthesis of c-di-GMP and propose a working model to explain the Cra-mediated regulatory mechanism that links carbon metabolism to host colonization. This study elucidates the regulatory role of Cra in bacterial attachment and colonization of plants, which raises the possibility of extending our studies to other bacteria associated with plant and human health.

scholarly journals GABARAPL2 Is Critical for Growth Restriction of Toxoplasma gondii in HeLa Cells Treated with Gamma Interferon

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Zhaoxia Zhang ◽  
Haorong Gu ◽  
Qi Li ◽  
Jun Zheng ◽  
Shinuo Cao ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Hela Cells ◽  
Critical Role ◽  
Gamma Interferon ◽  
Growth Restriction ◽  
Membrane Structures ◽  
Content Type ◽  
Receptor Associated Protein ◽  
Ifn Γ ◽  
And Function

ABSTRACT Gamma interferon (IFN-γ)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN-γ stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that γ-aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN-γ-treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding parasitophorous vacuoles (PV). Autophagy adaptors are required for the proper localization and function of GABARAPL2 in the IFN-γ -induced immune response. These findings provide further understanding of a noncanonical autophagy pathway responsible for IFN-γ-dependent inhibition of T. gondii growth in human HeLa cells and demonstrate the critical role of GABARAPL2 in this response.

scholarly journals Hydroxylamine and Carboxymethoxylamine Can Inhibit Toxoplasma gondii Growth through an Aspartate Aminotransferase-Independent Pathway

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Jixu Li ◽  
Huanping Guo ◽  
Eloiza May Galon ◽  
Yang Gao ◽  
Seung-Hun Lee ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Drug Targets ◽  
Protozoan Parasite ◽  
Cell Types ◽  
Lytic Cycle ◽  
Type I ◽  
Content Type ◽  
Mechanism Of Inhibition

ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan parasite and a successful parasitic pathogen in diverse organisms and host cell types. Hydroxylamine (HYD) and carboxymethoxylamine (CAR) have been reported as inhibitors of aspartate aminotransferases (AATs) and interfere with the proliferation in Plasmodium falciparum. Therefore, AATs are suggested as drug targets against Plasmodium. The T. gondii genome encodes only one predicted AAT in both T. gondii type I strain RH and type II strain PLK. However, the effects of HYD and CAR, as well as their relationship with AAT, on T. gondii remain unclear. In this study, we found that HYD and CAR impaired the lytic cycle of T. gondii in vitro, including the inhibition of invasion or reinvasion, intracellular replication, and egress. Importantly, HYD and CAR could control acute toxoplasmosis in vivo. Further studies showed that HYD and CAR could inhibit the transamination activity of rTgAAT in vitro. However, our results confirmed that deficiency of AAT in both RH and PLK did not reduce the virulence in mice, although the growth ability of the parasites was affected in vitro. HYD and CAR could still inhibit the growth of AAT-deficient parasites. These findings indicated that HYD and CAR inhibition of T. gondii growth and control of toxoplasmosis can occur in an AAT-independent pathway. Overall, further studies focusing on the elucidation of the mechanism of inhibition are warranted. Our study hints at new substrates of HYD and CAR as potential drug targets to inhibit T. gondii growth.

scholarly journals ROP16-Mediated Activation of STAT6 Suppresses Host Cell Reactive Oxygen Species Production, Facilitating Type III Toxoplasma gondii Growth and Survival

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Joshua A. Kochanowsky ◽  
Kaitlin K. Thomas ◽  
Anita A. Koshy
Keyword(s):  
Reactive Oxygen Species ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Parasite Growth ◽  
Effector Proteins ◽  
Oxygen Species ◽  
Content Type ◽  
Growth And Survival ◽  
Type Iii ◽  
Ifn Γ

ABSTRACT Polymorphic effector proteins determine the susceptibility of Toxoplasma gondii strains to IFN-γ-mediated clearance mechanisms deployed by murine host cells. However, less is known about the influence of these polymorphic effector proteins on IFN-γ-independent clearance mechanisms. Here, we show that deletion of one such polymorphic effector protein, ROP16, from a type III background leads to a defect in parasite growth and survival in unstimulated human fibroblasts and murine macrophages. Rescue of these defects requires a ROP16 with a functional kinase domain and the ability to activate a specific family of host cell transcription factors (STAT3, 5a, and 6). The growth and survival defects correlate with an accumulation of host cell reactive oxygen species (ROS) and are prevented by treatment with an ROS inhibitor. Exogenous activation of STAT3 and 6 suppresses host cell ROS production during infection with ROP16-deficient parasites and depletion of STAT6, but not STAT3 or 5a, causes an accumulation of ROS in cells infected with wild-type parasites. Pharmacological inhibition of NOX2 and mitochondrially derived ROS also rescues growth and survival of ROP16-deficient parasites. Collectively, these findings reveal an IFN-γ-independent mechanism of parasite restriction in human cells that is subverted by injection of ROP16 by type III parasites. IMPORTANCE Toxoplasma gondii is an obligate intracellular parasite that infects up to one-third of the world’s population. Control of the parasite is largely accomplished by IFN-γ-dependent mechanisms that stimulate innate and adaptive immune responses. Parasite suppression of IFN-γ-stimulated responses has been linked to proteins that the parasite secretes into its host cell. These secreted proteins vary by T. gondii strain and determine strain-specific lethality in mice. How these strain-specific polymorphic effector proteins affect IFN-γ-independent parasite control mechanisms in human and murine cells is not well known. This study shows that one such secreted protein, ROP16, enables efficient parasite growth and survival by suppressing IFN-γ-independent production of ROS by human and mouse cells.

scholarly journals The Vacuolar Zinc Transporter TgZnT Protects Toxoplasma gondii from Zinc Toxicity

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Nathan M. Chasen ◽  
Andrew J. Stasic ◽  
Beejan Asady ◽  
Isabelle Coppens ◽  
Silvia N. J. Moreno
Keyword(s):  
Toxoplasma Gondii ◽  
Metal Ion ◽  
Essential Element ◽  
Lytic Cycle ◽  
Zinc Toxicity ◽  
Content Type ◽  
Zinc Concentrations ◽  
High Concentrations ◽  
Yeast Mutants

ABSTRACT Zinc (Zn2+) is the most abundant biological metal ion aside from iron and is an essential element in numerous biological systems, acting as a cofactor for a large number of enzymes and regulatory proteins. Zn2+ must be tightly regulated, as both the deficiency and overabundance of intracellular free Zn2+ are harmful to cells. Zn2+ transporters (ZnTs) play important functions in cells by reducing intracellular Zn2+ levels by transporting the ion out of the cytoplasm. We characterized a Toxoplasma gondii gene (TgGT1_251630, TgZnT), which is annotated as the only ZnT family Zn2+ transporter in T. gondii. TgZnT localizes to novel vesicles that fuse with the plant-like vacuole (PLV), an endosome-like organelle. Mutant parasites lacking TgZnT exhibit reduced viability in in vitro assays. This phenotype was exacerbated by increasing zinc concentrations in the extracellular media and was rescued by media with reduced zinc. Heterologous expression of TgZnT in a Zn2+-sensitive Saccharomyces cerevisiae yeast strain partially restored growth in media with higher Zn2+ concentrations. These results suggest that TgZnT transports Zn2+ into the PLV and plays an important role in the Zn2+ tolerance of T. gondii extracellular tachyzoites. IMPORTANCE Toxoplasma gondii is an intracellular pathogen of human and animals. T. gondii pathogenesis is associated with its lytic cycle, which involves invasion, replication, egress out of the host cell, and invasion of a new one. T. gondii must be able to tolerate abrupt changes in the composition of the surrounding milieu as it progresses through its lytic cycle. We report the characterization of a Zn2+ transporter of T. gondii (TgZnT) that is important for parasite growth. TgZnT restored Zn2+ tolerance in yeast mutants that were unable to grow in media with high concentrations of Zn2+. We propose that TgZnT plays a role in Zn2+ homeostasis during the T. gondii lytic cycle.

scholarly journals The Functional Structure of Central Carbon Metabolism in Pseudomonas putida KT2440

2014 ◽  
Vol 80 (17) ◽  
pp. 5292-5303 ◽  
Author(s):  
Suresh Sudarsan ◽  
Sarah Dethlefsen ◽  
Lars M. Blank ◽  
Martin Siemann-Herzberg ◽  
Andreas Schmid
Keyword(s):  
Pseudomonas Putida ◽  
Carbon Metabolism ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Central Metabolism ◽  
Content Type ◽  
Central Carbon ◽  
Definition Of

ABSTRACTWhat defines central carbon metabolism? The classic textbook scheme of central metabolism includes the Embden-Meyerhof-Parnas (EMP) pathway of glycolysis, the pentose phosphate pathway, and the citric acid cycle. The prevalence of this definition of central metabolism is, however, equivocal without experimental validation. We address this issue using a general experimental approach that combines the monitoring of transcriptional and metabolic flux changes between steady states on alternative carbon sources. This approach is investigated by using the model bacteriumPseudomonas putidawith glucose, fructose, and benzoate as carbon sources. The catabolic reactions involved in the initial uptake and metabolism of these substrates are expected to show a correlated change in gene expressions and metabolic fluxes. However, there was no correlation for the reactions linking the 12 biomass precursor molecules, indicating a regulation mechanism other than mRNA synthesis for central metabolism. This result substantiates evidence for a (re)definition of central carbon metabolism including all reactions that are bound to tight regulation and transcriptional invariance. Contrary to expectations, the canonical Entner-Doudoroff and EMP pathwayssensu strictoare not a part of central carbon metabolism inP. putida, as they are not regulated differently from the aromatic degradation pathway. The regulatory analyses presented here provide leads on a qualitative basis to address the use of alternative carbon sources by deregulation and overexpression at the transcriptional level, while rate improvements in central carbon metabolism require careful adjustment of metabolite concentrations, as regulation resides to a large extent in posttranslational and/or metabolic regulation.

scholarly journals Effects of PERK eIF2α Kinase Inhibitor against Toxoplasma gondii

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Leonardo Augusto ◽  
Jennifer Martynowicz ◽  
Kirk A. Staschke ◽  
Ronald C. Wek ◽  
William J. Sullivan
Keyword(s):  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Er Stress ◽  
Lethal Dose ◽  
Lytic Cycle ◽  
Host Cells ◽  
Initiation Factor ◽  
Α Subunit ◽  
Content Type ◽  
Eif2α Kinase

ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that has infected one-third of the population. Upon infection of warm-blooded vertebrates, the replicating form of the parasite (tachyzoite) converts into a latent form (bradyzoite) present in tissue cysts. During immune deficiency, bradyzoites can reconvert into tachyzoites and cause life-threatening toxoplasmosis. We previously reported that translational control through phosphorylation of the α subunit of T. gondii eukaryotic initiation factor 2 (eIF2α) (TgIF2α) is a critical component of the parasite stress response. Diverse stresses can induce the conversion of tachyzoites to bradyzoites, including those disrupting the parasite's endoplasmic reticulum (ER) (ER stress). Toxoplasma possesses four eIF2α kinases, one of which (TgIF2K-A) localizes to the parasite ER analogously to protein kinase R-like endoplasmic reticulum kinase (PERK), the eIF2α kinase that responds to ER stress in mammalian cells. Here, we investigated the effects of a PERK inhibitor (PERKi) on Toxoplasma. Our results show that the PERKi GSK2606414 blocks the enzymatic activity of TgIF2K-A and reduces TgIF2α phosphorylation specifically in response to ER stress. PERKi also significantly impeded multiple steps of the tachyzoite lytic cycle and sharply lowered the frequency of bradyzoite differentiation in vitro. Pretreatment of host cells with PERKi prior to infection did not affect parasite infectivity, and PERKi still impaired parasite replication in host cells lacking PERK. In mice, PERKi conferred modest protection from a lethal dose of Toxoplasma. Our findings represent the first pharmacological evidence supporting TgIF2K-A as an attractive new target for the treatment of toxoplasmosis.

scholarly journals Intracellular Acetyl Unit Transport in Fungal Carbon Metabolism

2010 ◽  
Vol 9 (12) ◽  
pp. 1809-1815 ◽  
Author(s):  
Karin Strijbis ◽  
Ben Distel
Keyword(s):  
Carbon Metabolism ◽  
Citrate Synthase ◽  
Current Knowledge ◽  
Glyoxylate Cycle ◽  
Carbon Sources ◽  
Fungal Species ◽  
Special Focus ◽  
Acetyl Coa ◽  
Content Type ◽  
Dependent Pathway

ABSTRACT Acetyl coenzyme A (acetyl-CoA) is a central metabolite in carbon and energy metabolism. Because of its amphiphilic nature and bulkiness, acetyl-CoA cannot readily traverse biological membranes. In fungi, two systems for acetyl unit transport have been identified: a shuttle dependent on the carrier carnitine and a (peroxisomal) citrate synthase-dependent pathway. In the carnitine-dependent pathway, carnitine acetyltransferases exchange the CoA group of acetyl-CoA for carnitine, thereby forming acetyl-carnitine, which can be transported between subcellular compartments. Citrate synthase catalyzes the condensation of oxaloacetate and acetyl-CoA to form citrate that can be transported over the membrane. Since essential metabolic pathways such as fatty acid β-oxidation, the tricarboxylic acid (TCA) cycle, and the glyoxylate cycle are physically separated into different organelles, shuttling of acetyl units is essential for growth of fungal species on various carbon sources such as fatty acids, ethanol, acetate, or citrate. In this review we summarize the current knowledge on the different systems of acetyl transport that are operational during alternative carbon metabolism, with special focus on two fungal species: Saccharomyces cerevisiae and Candida albicans.

scholarly journals Signaling Cascades Governing Entry into and Exit from Host Cells by Toxoplasma gondii

2019 ◽  
Vol 73 (1) ◽  
pp. 579-599 ◽  
Author(s):  
Hugo Bisio ◽  
Dominique Soldati-Favre
Keyword(s):  
Toxoplasma Gondii ◽  
Conceptual Framework ◽  
Lytic Cycle ◽  
Host Cells ◽  
Current Understanding ◽  
Signaling Cascades ◽  
Protozoan Parasites ◽  
Obligate Intracellular ◽  
Warm Blooded Animal ◽  
Infected Cells

The Apicomplexa phylum includes a large group of obligate intracellular protozoan parasites responsible for important diseases in humans and animals. Toxoplasma gondii is a widespread parasite with considerable versatility, and it is capable of infecting virtually any warm-blooded animal, including humans. This outstanding success can be attributed at least in part to an efficient and continuous sensing of the environment, with a ready-to-adapt strategy. This review updates the current understanding of the signals governing the lytic cycle of T. gondii, with particular focus on egress from infected cells, a key step for balancing survival, multiplication, and spreading in the host. We cover the recent advances in the conceptual framework of regulation of microneme exocytosis that ensures egress, motility, and invasion. Particular emphasis is given to the trigger molecules and signaling cascades regulating exit from host cells.

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