Research focus

We aim to understand the exit strategy of Trypanosoma cruzi, a human pathogen causing Chagas disease. This work is a fundamental piece in our understanding of disease progression and in the challenging venture of new anti-chagasic drug discovery.

Egress is a critical step of the life cycle for many intracellular pathogens. While the cellular strategies adopted by different organisms are diverse (programmed cell-death, exit without host cell lysis or active lytic destruction), the host cell exit is intimately linked to pathogenesis, spread of the disease and transmission.

Life-long infection with the intracellular parasite Trypanosoma cruziunderlies the development of human chronic Chagas disease causing severe cardiac, digestive, or neurological alterations. During the acute and chronic phase of the infection, effective and timely regulated parasite egress is crucial for the parasite survival and persistence. Despite its importance in disease progression and symptoms, the molecular mechanisms of active T. cruzi exit from its host cell are unknown.

What is the dynamic of the host cytoskeleton during infection?

Intracellular T. cruzi resides free in the host cell cytoplasm and depends on host metabolic resources and host organelles interaction for its growth. During infection, an extensive remodelling of the host cytoskeleton has been observed. This peculiar cytoskeletal arrangement, driven by the infection, suddenly break down right before host cell lysis and egress of the parasite. We aim to study the dynamic of different cytoskeletal elements before and during the egress process to understand which structures T. cruzi destabilizes to facilitate its exit from the host cell.

Which are the molecular players of active host cell exit?

During decades, T. cruzi exit has been attributed to the extensive parasite motility, thought to be sufficient to induce mechanical rupture of the host cell membrane. However, recent work and observations revealed that T. cruzi egress is an event driven by the parasite. As for many pathogens, the timing and mechanisms underlying T. cruzi egress are highly controlled and very much parasite specific. By combining genetic manipulation and cutting-edge mass spectrometry technologies, we aim to identify and functionally characterized the molecular players responsible of the sudden host cell lysis and parasite release in T. cruzi. Our work would have a significant impact on the scientific community and for patients and populations negatively affected by this infection.

Publications

Toxoplasma gondii rhoptry discharge factor 3 is essential for invasion and microtubule-associated vesicle biogenesis. Chaabene R B, Martinez M, Bonavoglia A, Maco B, Chang Y-W, Lentini G, Soldati-Favre D. PLoS Biol (2024)

Cytokinetic abscission in Toxoplasma gondii is governed by protein phosphatase 2A and the daughter cell scaffold complex. Marq J-B, Gosetto M, Altenried A, Vadas O, Maco B, Pacheco N D S, Tosetti N, Soldati-Favre D, Lentini G. EMBO J (2024)

Ceramide biosynthesis is critical for establishment of the intracellular niche of Toxoplasma gondii. Nyonda MA, Kloehn J, Sosnowski P, Krishnan A, Lentini G, Maco B, Marq JB, Hannich JT, Hopfgartner G, Soldati-Favre D. Cell reports (2022)

Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion. Lentini G, Ben Chaabene R, Vadas O, Ramakrishnan C, Mukherjee B, Mehta V, Lunghi M, Grossmann J, Maco B, Visentin R, Hehl AB, Korkhov VM, Soldati-Favre D. Nature Communications (2021)

The roles of Centrin2 and Dynein Light Chain 8a in apical secretory organelles discharges of Toxoplasma gondii. Lentini G, Dubois DJ, Maco B, Soldati-Favre D, Frenal K. Traffic (2019).

Targeting host mitochondria: A role for the Trypanosoma cruzi amastigote flagellum.  Lentini G, Dos Santos Pacheco N, Burleigh B. Cellular Microbiology (2018).

Modulation of host central carbon metabolism and in situ glucose uptake by intracellular Trypanosoma cruziamastigotes. Shah Simpson S, Lentini G, Dumoulin PC, Burleigh B. PLoS Pathogens (2017).

A lipid-binding protein mediates rhoptry discharge and invasion in Plasmodium falciparum and Toxoplasma gondiiparasites. Suarez C, Lentini G, Ramaswamy R, Maynadier M, Aquilini E, Berry-Sterkers L, Cipriano M, Chen A, Bradley P, Striepen B, Boulanger M, Lebrun M. Nature Communications (2019).

Characterization of Toxoplasma DegP, a rhoptry serine protease crucial for lethal infection in mice. Lentini G, El Hajj H, Papoin J, Fall G, Pfaff AW, Tawil N, Braun-Breton C, Lebrun M. PLoS One (2017).

Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. Wang K, Peng ED, Huang AS, Xia D, Vermont SJ, Lentini G, Lebrun M, Wastling JM, Bradley PJ. PLoS One (2016).

Identification and characterization of Toxoplasma SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite. Lentini G, Kong-Hap M, El Hajj H, Francia ME, Claudet C, Striepen B, Dubremetz JF, Lebrun M. Cellular Microbiology (2015).

Lipid kinases are essential for apicoplast homeostasis in Toxoplasma gondii. Daher W, Morlon-Guyot J, Sheiner L, Lentini G, Berry L, Tawk L, Dubremetz JF, Wengelnik K, Striepen B, Lebrun M. Cellular Microbiology (2015).

Identification of a new rhoptry neck complex RON9/RON10 in the Apicomplexa parasite Toxoplasma gondii. Lamarque MH, Papoin J, Finizio AL, Lentini G, Pfaff AW, Candolfi E, Dubremetz JF, Lebrun M. PLoS One (2012).

Books and Reviews

Biogenesis and discharge of the rhoptries: key organelles for entry and hijack of host cells by the Apicomplexa. Ben Chaabene R, Lentini G, Soldati-Favre D. Molecular Microbiology (2020).

Intracellular Parasites:Kinetoplastids. Lentini G., Dumoulin PC., Carter NS. Encyclopedia of Cell Biology, Second Edition. Elsevier Inc. (2022).