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Last name: LEMICHEZ
First name: Emmanuel
International audience
The CNF1 toxin is produced by some uropathogenic (UPECs) andmeningitis-causing Escherichia coli strains. It belongs to a large family of bacterial virulence factors and toxins modifying cellular regulators of the actin cytoskeleton, namely the Rho GTPases. CNF1 autonomously enters the host cell cytosol, where it catalyzes the constitutive...
Functional and structural studies highlight the remarkable evolution and features of the typhoid toxin from Salmonella Typhi. This reveals that attachment of the toxin to specific N-glycan chains accounts for its tropism for selected human tissues.
The monitoring of the activation state of Rho GTPases has emerged as a potent innate immune mechanism for detecting pathogens. In the March issue of PLOS Pathogens, we show that the activation of Rho GTPases by the CNF1 toxin during E. coli-triggered bacteremia leads to a GR1(+)cell-mediated efficient bacterial clearing and improves host...
Studies on deamidase toxins continue to reveal unexpected molecular mechanisms that are relevant to many fields of biology. This holds true for the discovery of the regulation of small GTPases by ubiquitin-mediated proteasomal degradation, as well as the identification of key factors controlling these cellular regulations. A growing body of...
International audience
The CNF1 toxin is produced by uropathogenic and meningitis-causing Escherichia coli. CNF1 catalyzes the constitutive activation of Rho proteins by deamidation. The threshold of activation of Rho proteins by CNF1 is, however, attenuated because of a concomitant decrease of their cellular levels. Depletion of activated-Rac1 is catalyzed by...
Dewetting is the spontaneous withdrawal of a liquid film from a non-wettable surface by nucleation and growth of dry patches. Two recent reports now propose that the principles of dewetting explain the physical phenomena underpinning the opening of transendothelial cell macroaperture (TEM) tunnels, referred to as cellular dewetting. This was...
Dewetting is the spontaneous withdrawal of a liquid film from a non-wettable surface by nucleation and growth of dry patches. Two recent reports now propose that the principles of dewetting explain the physical phenomena underpinning the opening of transendothelial cell macroaperture (TEM) tunnels, referred to as cellular dewetting. This was...
Introducing concepts from soft matter physics and mechanics has largely contributed to our understanding of a variety of biological processes. In this review, we argue that this holds true for bacterial pathogenesis. We base this argument on three examples of bacterial pathogens and their interaction with host cells during infection: (i)...
Cytotoxic necrotizing factor 1 (CNF1) from uropathogenic Escherichia coli belongs to a family of factors activating Rho GTPases. We report the in vivo effects of CNF1 in mice co-fed toxin and the soluble protein antigen ovalbumin (OVA). Similar to cholera toxin, CNF1 elicits adjuvanticity anti-OVA responses, both systemic and mucosal. In...
Staphylococcus aureus, a major causative agent of human infection, produces a large array of virulence factors, including various toxins. Among them, the host RhoA GTPase ADP-ribosylating EDIN toxins are considered as potential virulence factors. Using the polymerase chain reaction (PCR) assay, we analyzed the virulence profile of 256 isolates...
Interleukin-8 elevation in urine during urinary tract infections (UTIs) has been documented for different uropathogenic germs in 85 patients. We showed that for 17 different isolates, IL-8 was increased in 92% of UTIs with an average value of 627 pg/ml for infected, as compared to 45 pg/ml for uninfected patients. We suggest that the high...
The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84...
The endothelium serves as a protective semipermeable barrier in blood vessels and lymphatic vessels. Leukocytes and pathogens can pass directly through the endothelium by opening holes in endothelial cells, known as transcellular tunnels, which are formed by contact and self-fusion of the apical and basal plasma membranes. Here we test the...
International audience
BAR domain proteins contribute to membrane deformation in diverse cellular processes. The inverted-BAR (I-BAR) protein IRSp53, for instance, is found on the inner leaflet of the tubular membrane of filopodia; however its role in the formation of these structures is incompletely understood. Here we develop an original assay in which proteins are...
Here we engineered transgenic Leishmania infantum that express luciferase, the objectives being to more easily monitor in real time their establishment either in BALB/c mice--the liver and spleen being mainly studied-or in vitro. Whatever stationary phase L. infantum promastigotes population--wild type or engineered to express luciferase-the...
There is a need to develop new effective immunoadjuvants for prophylactic or therapeutic vaccines against intracellular pathogens. The activation of Rho GTPases by bacterial cytotoxic necrotizing factor 1 (CNF1) elicits humoral protective responses against protein antigens. Here, we set out to investigate whether CNF1 activity initiates humoral...
cAMP and cyclic GMP-dependent kinases (PKA and PKG) phosphorylate the small G protein RhoA on Ser188. We have previously demonstrated that phosphorylation of Ser188 inhibits RhoA-dependent functions and positively regulates RhoA expression, and that the nitric oxide (NO)/cGMP-dependent protein kinase pathway plays an essential role, both in...
Cytotoxic necrotizing factor 1 (CNF1) is a toxin produced by pathogenic strains of Escherichia coli responsible for extra‐intestinal infections. CNF1 deamidates Rac1, thereby triggering its permanent activation and worsening inflammatory reactions. Activated Rac1 is prone to proteasomal degradation. There is no targeted therapy against CNF1,...