News
JuLY 2024
Read our new review about Dictyostelium discoideum–Mycobacterium marinum as an infection model of tuberculosis
Mycobacterium tuberculosis is a pathogenic mycobacterium that causes tuberculosis. Tuberculosis is a significant global health concern that poses numerous clinical challenges, particularly in terms of finding effective treatments for patients. Throughout evolution, host immune cells have developed cell-autonomous defence strategies to restrain and eliminate mycobacteria. Concurrently, mycobacteria have evolved an array of virulence factors to counteract these host defences, resulting in a dynamic interaction between host and pathogen. Here, we review recent findings, including those arising from the use of the amoeba D. discoideum as a model to investigate key mycobacterial infection pathways. D. discoideum serves as a scalable and genetically tractable model for human phagocytes, providing valuable insights into the intricate mechanisms of host–pathogen interactions. We are highlighting the similarities between M. tuberculosis and M. marinum and their experimental hosts (macrophages and D. discoideum respectively)
Click here if you want to know more !
Our new Methods chapter is out! How to follow membrane damage and repair processes in D. discoideum ...
Using the social amoeba Dictyostelium discoideum as a model, we investigate the mechanisms of membrane damage response and repair. This model system is crucial for identifying factors involved in plasma and endolysosomal membrane maintenance. Additionally, it allows us to phenotype mutant strains and quantify cell fitness and gene function through live cell microscopy, thereby enhancing our understanding of the cellular processes essential for membrane repair and homeostasis. If you want to know more, you can read it here.
Here D. discoideum expresses the GFP-Vps32 protein as a reporter for membrane damage repair. An accumulation of GFP-Vps32 positive structures can be observed in the cells after treatment with a sterile damage inducing agent (LLoMe).
JUNE 2024
Warm welcome to two new master students in the lab !
Sandra Valero Cardoso is doing her MSc in Biochemistry at the University of Geneva. 
Sandra will be investigating the role of STAT genes in Dictyostelium discoideum, key to the immune response during Mycobacterium marinum infection. The aim is to gain insight into the nuclear translocation of STATs after exposure to different stresses using fluorescence microscopy. We will also determine the phosphorylation, which precedes nuclear translocation, of STATs during infection by using a Phos-tag approach.
Laria Jradi is pursuing a Master's degree in Pharmacy at the University of Geneva.
Laria will be working at testing new natural anti-mycobacterial compounds using our Dictyostelium discoideum-Mycobacterium marinum platform. And who knows, she might even discover a new treatment !
FebruarY 2024
A new visitor in the team for a few months! 
Carolina Panosso Schuindt, a bachelor student from the Freire Neto group in São Paulo, joined us for three months, thanks to the support of FAPESP, in order to work on the interaction between D. discoideum and a colorful opportunistic pathogen, Chromobacterium violaceum.
"As part of my research at the University of São Paulo (Brazil), I characterized the role of ZntA and ZntR in the context of zinc and cadmium intoxication in the opportunistic pathogen Chromobacterium violaceum(Cv). Now I have joined the Soldati lab for a 3-month internship, and under the supervision of Dr. Lucas Ceseti, I will investigate what happens when Dicty meets Cv and whether ZntA and ZntR are essential for the bacterial virulence in the context of infection." - Carolina Panosso Schuindt
Congratulations to Crisalida for her successful master's defense !
After a year with us, Crisalida successfully defended her master's work. She worked at investigating the role of lipophagy in lipid droplet dynamics in D. discoideum. She will continue her work with us for few months, before to start her PhD in another team at Unige 
January 2024
New paper out in mSystems: Temporal genome-wide fitness analysis of Mycobacterium marinum during infection reveals the genetic requirement of virulence and survival in amoebae and microglial cells
In this pivotal study, our lab, in collaboration with the team of Pr. Graham Stewart, has identified critical genes essential for mycobacterial survival during the infection. Tuberculosis, a persistent infectious disease, has become even more challenging with the rise of drug-resistant strains, necessitating improved treatment strategies. Utilizing transposon sequencing (Tn-Seq) on Mycobacterium marinum (a model pathogen for M. tuberculosis), we pinpointed genes crucial for infection survival. This unbiased genome-wide approach highlighted disruptions in 57% of TA sites and identified 568 essential genes (10.2%). Noteworthy pathways for M. marinum survival during infection in different host cells included DNA damage repair, lipid and vitamin metabolism, the type VII secretion system (T7SS) ESX-1, and the Mce1 lipid transport system. These findings, consistent with previous studies, provide valuable insights into tuberculosis pathogenesis, offering potential targets for more effective drug interventions.
For the complete story, click here!
New collaborative paper with Philippe Dehio in the team of Prof. Christoph Hess: An evolutionary-conserved VPS34-PIKfyve-TRPML1-Myosin II axis regulates the speed of amoeboid cell migration
In this new collaborative work, a crucial connection between ultrastructural polarization and T cell migration signaling have been unveiled. This study led by the team of Prof. Hess, identifies endo-lysosome-localized kinases, specifically VPS34–PIKfyve, as instrumental in regulating the speed of amoeboid migration in T cells. The research demonstrates the accumulation of these kinases at the uropod of polarized cells, influencing T cell velocity without altering directionality. The mechanism involves the generation of PI(3,5)P2, controlling Ca2+ efflux through TRPML1 and subsequently regulating myosin IIA activity and propulsive force via retrograde actin flow. Notably, the study also highlights the evolutionary conservation of the VPS34–PIKfyve axis in controlling migration speed in myeloid cells and Dictyostelium discoideum.
Have a look here!
OCTOBER 2023
An SNSF grant has been assigned to our group !
We are delighted to announce that our group has been granted an SNSF grant to work on the virulence strategies of pathogenic mycobacteria and cell-autonomous host defence mechanisms. We are happy to continue our strong contribution to the field with our unique model !
New collaborative paper with the Wolfender group out in Frontiers in Natural Products: Targeted isolation of natural analogs of anti-mycobacterial hit compounds based on the metabolite profiling of a large collection of plant extracts
Antibiotics resistance is a clear threat to the future of current tuberculosis treatments like rifampicin, prompting the need for new treatment options in this field. While plants can offer a plethora of chemical diversity in their constitutive natural products to tackle this issue, finding potentially bioactive compounds in them has not always proven to be that simple. Classical bioactivity-guided fractionation approaches are still trendy, but they bear significant shortfalls, like their time-consuming nature as well as the ever-increasing risk of isolating known bioactive compounds. In this regard, we have developed an alternative method to the latter approach that allows for natural derivatives of a known bioactive scaffold to be efficiently targeted and isolated within a large library of plant extracts. Hence our approach allows for the anticipation of bioactive structure independently of preliminary bioassays. By relying on the chemical diversity of a set of 1,600 plant extracts analyzed by HRMS/MS, we were able to isolate and characterize several minor derivatives of a previously reported bioactive aza-anthraquinone compound from Cananga brandisiana, selected within the plant set. Assessment of bioactivity on these derivatives confirmed their expected activity on Mycobacterium marinum in our anti-infective assay. This proof-of-concept study has established an original path towards bioactive compounds isolation, with the advantage of potentially highlighting minor bioactive compounds, whose activity may not even be detectable at the extract level.
For a complete reading, it's here.
AUGUST 2023
Master internship
We are looking for two motivated master students to join our lab and collaborate on our most recent stories: TrafE and Vacuolins
Don't hesitate to check our Job offers page !
June 2023
Very exciting news! Our postdoc Sandra Guallar-Garrido has been awarded an SNF postdoctoral fellowship!
This fellowship will allow here to keep deciphering the role of TrafE during M. marinum infection in Dicty. Huge congratulations to her!
New collaborative paper with the team of Jason King out in Journal of Cell Biology: A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes
Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity. However PI(3,5)P2 dynamics and regulation remain unclear due to lack of reliable reporters. Using the amoeba Dictyostelium discoideum we identify SnxA as a highly-selective PI(3,5)P2 -binding protein and characterise its use as a reporter for PI(3,5)P2 in both Dictyostelium and mammalian cells. Using GFP-SnxA we demonstrate that Dictyostelium phagosomes and macropinosomes accumulate PI(3,5)P2 three minutes after engulfment but is then retained differently, indicating pathway-specific regulation. We further find that PIKfyve recruitment and activity are separable, and that PIKfyve activation stimulates its own dissociation. SnxA is therefore a new tool for reporting PI(3,5)P2 in live cells that reveals key mechanistic details of the role and regulation of PIKfyve/PI(3,5)P2 .
Have a look here!
APRIL 2023
New paper out in eLife: A TRAF-like E3 ubiquitin ligase TrafE coordinates ESCRT and autophagy in endolysosomal damage response and cell-autonomous immunity to Mycobacterium marinum
Cells are perpetually challenged by pathogens, protein aggregates or chemicals, that induce plasma membrane or endolysosomal compartments damage. This severe stress is recognised and controlled by the endosomal sorting complex required for transport (ESCRT) and the autophagy machineries, which are recruited to damaged membranes to either repair or to remove membrane remnants. Yet, insight is limited about how damage is sensed and which effectors lead to extensive tagging of the damaged organelles with signals, such as K63-polyubiquitin, required for the recruitment of membrane repair or removal machineries. To explore the key factors responsible for detection and marking of damaged compartments, we use the professional phagocyte Dictyostelium discoideum. We found an evolutionary conserved E3-ligase, TrafE, that is robustly recruited to intracellular compartments disrupted after infection with Mycobacterium marinum or after sterile damage caused by chemical compounds. TrafE acts at the intersection of ESCRT and autophagy pathways and plays a key role in functional recruitment of the ESCRT subunits ALIX, Vps32 and Vps4 to damage sites. Importantly, we show that the absence of TrafE severely compromises the xenophagy restriction of mycobacteria as well as ESCRT-mediated and autophagy-mediated endolysosomal membrane damage repair, resulting in early cell death.
For the complete story, click here!
MARCH 2023
We have a new postdoctoral fellow in the lab!
Justine Toinon join us for a project on the exploration of the signaling cascades and transcriptional reprogramming in the course of Mycobacterium marinum infection both in Dictyostelium discoideum and in murine microglial cells. Let's give her a warm welcome!
We have a new postdoctoral fellow in the lab!
After his stay last year, Lucas Ceseti decided to come back and join us as a postdoctoral fellow for a project on elucidating the strategies used by X. citri to resist predation by D. discoideum. Let's give him a warm welcome!
November 2022
New collaborative paper: 5-ethyl-2’-deoxyuridine fragilizes Klebsiella pneumoniae outer wall and facilitates intracellular killing by phagocytic cells
Our team collaborated with the team of Prof. Pierre Cosson on this work that allowed the identification of a new antibacterial compound targeting K. pneumoniae and facilitating its killing by Dicty. You can learn a bit more about this story here, or directly read the paper published in PLOS One here.
Klebsiella pneumoniae is the causative agent of a variety of severe infections. Many K. pneumoniae strains are resistant to multiple antibiotics, and this situation creates a need for new antibacterial molecules. K. pneumoniae pathogenicity relies largely on its ability to escape phagocytosis and intracellular killing by phagocytic cells. Interfering with these escape mechanisms may allow to decrease bacterial virulence and to combat infections. In this study, we used Dictyostelium discoideum as a model phagocyte to screen a collection of 1,099 chemical compounds. Phg1A KO D. discoideum cells cannot feed upon K. pneumoniae bacteria, unless bacteria bear mutations decreasing their virulence. We identified 3 non-antibiotic compounds that restored growth of phg1A KO cells on K. pneumoniae, and we characterized the mode of action of one of them, 5-ethyl-2’-deoxyuridine (K2). K2-treated bacteria were more rapidly killed in D. discoideum phagosomes than non-treated bacteria. They were more sensitive to polymyxin and their outer membrane was more accessible to a hydrophobic fluorescent probe. These results suggest that K2 acts by rendering the membrane of K. pneumoniae accessible to antibacterial effectors. K2 was effective on three different K. pneumoniae strains, and acted at concentrations as low as 3 μM. K2 has previously been used to treat viral infections but its precise molecular mechanism of action in K. pneumoniae remains to be determined.
September 2022
A new collaborative work with Dr. Cristina Alvarez-Martinez from the Universidade Estadual de Campinas (Brazil) supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and the Swiss National Science Foundation (SNSF)
Thanks to a research grant, the FAPESP and the SNSF will support a new collaborative work with Dr. Cristina Alvarez-Martinez. This project will aim at deciphering the molecular mechanisms of the Xanthomonas citri resistance to Dictyostelium discoideum predation and the role of the Type VI Secretion System (T6SS) (A) of X. citri in this resistance. Overall, this project will expand our understanding of the role of anti-eukaryotic T6SS and possibly reveal new effector functions and anti-host strategies. This will help to understand better the mechanisms used by X. citri to survive and disseminate in the environment (B).