Publications

@article{pmid28698636,

title = {Standardized Nanomechanical Atomic Force Microscopy Procedure (SNAP) for Measuring Soft and Biological Samples},

author = {Hermann Schillers and Carmela Rianna and Jens Schäpe and Tomas Luque and Holger Doschke and Mike Wälte and Juan José Uriarte and Noelia Campillo and Georgios P A Michanetzis and Justyna Bobrowska and Andra Dumitru and Elena T Herruzo and Simone Bovio and Pierre Parot and Massimiliano Galluzzi and Alessandro Podestà and Luca Puricelli and Simon Scheuring and Yannis Missirlis and Ricardo Garcia and Michael Odorico and Jean-Marie Teulon and Frank Lafont and Malgorzata Lekka and Felix Rico and Annafrancesca Rigato and Jean-Luc Pellequer and Hans Oberleithner and Daniel Navajas and Manfred Radmacher},

doi = {10.1038/s41598-017-05383-0},

issn = {2045-2322},

year  = {2017},

date = {2017-01-01},

journal = {Sci Rep},

volume = {7},

number = {1},

pages = {5117},

abstract = {We present a procedure that allows a reliable determination of the elastic (Young's) modulus of soft samples, including living cells, by atomic force microscopy (AFM). The standardized nanomechanical AFM procedure (SNAP) ensures the precise adjustment of the AFM optical lever system, a prerequisite for all kinds of force spectroscopy methods, to obtain reliable values independent of the instrument, laboratory and operator. Measurements of soft hydrogel samples with a well-defined elastic modulus using different AFMs revealed that the uncertainties in the determination of the deflection sensitivity and subsequently cantilever's spring constant were the main sources of error. SNAP eliminates those errors by calculating the correct deflection sensitivity based on spring constants determined with a vibrometer. The procedure was validated within a large network of European laboratories by measuring the elastic properties of gels and living cells, showing that its application reduces the variability in elastic moduli of hydrogels down to 1%, and increased the consistency of living cells elasticity measurements by a factor of two. The high reproducibility of elasticity measurements provided by SNAP could improve significantly the applicability of cell mechanics as a quantitative marker to discriminate between cell types and conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28484683,

title = {Alterations of the  Replicative Vacuole Membrane Integrity and Interplay with the Autophagy Pathway},

author = {María E Mansilla Pareja and Antonino Bongiovanni and Frank Lafont and María I Colombo},

doi = {10.3389/fcimb.2017.00112},

issn = {2235-2988},

year  = {2017},

date = {2017-01-01},

journal = {Front Cell Infect Microbiol},

volume = {7},

pages = {112},

abstract = {, the etiologic agent of Q fever, is a Gram-negative obligate intracellular bacterium. It has been previously described that both the endocytic and autophagic pathways contribute to the  replicative vacuole (CRV) generation. Galectins are β-galactoside-binding lectins that accumulate in the cytosol before being secreted via a non-conventional secretory pathway. It has been shown that Galectin-3, -8, -9 monitor bacteria vacuolar rupture and endosomal and lysosomal loss of membrane integrity through binding of host glycans exposed in the cytoplasm after membrane damage. Using microinjection of fluorescence-coupled dextrans, a FRET assay, and galectins distribution, we demonstrate that  infection actually result in transient phagosomal/CRV membrane damage in a Dot/Icm-dependent manner. We also show the association of different adaptor molecules involved in autophagy and of LC3 to the limiting membrane of the CRV. Moreover, we show that upon autophagy inhibition, the proportion of CRVs labeled with galectins and less acidified increases which is associated with bacteria replication impairment. Based on these observations, we propose that autophagy can facilitate resealing of intracellular damaged membranes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28112163,

title = {Developmental Expression of 4-Repeat-Tau Induces Neuronal Aneuploidy in Drosophila Tauopathy Models},

author = {Nicolas Malmanche and Pierre Dourlen and Marc Gistelinck and Florie Demiautte and Nichole Link and Cloé Dupont and Lies Vanden Broeck and Elisabeth Werkmeister and Philippe Amouyel and Antonino Bongiovanni and Hélène Bauderlique and Dieder Moechars and Anne Royou and Hugo J Bellen and Frank Lafont and Patrick Callaerts and Jean-Charles Lambert and Bart Dermaut},

doi = {10.1038/srep40764},

issn = {2045-2322},

year  = {2017},

date = {2017-01-01},

journal = {Sci Rep},

volume = {7},

pages = {40764},

abstract = {Tau-mediated neurodegeneration in Alzheimer's disease and tauopathies is generally assumed to start in a normally developed brain. However, several lines of evidence suggest that impaired Tau isoform expression during development could affect mitosis and ploidy in post-mitotic differentiated tissue. Interestingly, the relative expression levels of Tau isoforms containing either 3 (3R-Tau) or 4 repeats (4R-Tau) play an important role both during brain development and neurodegeneration. Here, we used genetic and cellular tools to study the link between 3R and 4R-Tau isoform expression, mitotic progression in neuronal progenitors and post-mitotic neuronal survival. Our results illustrated that the severity of Tau-induced adult phenotypes depends on 4R-Tau isoform expression during development. As recently described, we observed a mitotic delay in 4R-Tau expressing cells of larval eye discs and brains. Live imaging revealed that the spindle undergoes a cycle of collapse and recovery before proceeding to anaphase. Furthermore, we found a high level of aneuploidy in post-mitotic differentiated tissue. Finally, we showed that overexpression of wild type and mutant 4R-Tau isoform in neuroblastoma SH-SY5Y cell lines is sufficient to induce monopolar spindles. Taken together, our results suggested that neurodegeneration could be in part linked to neuronal aneuploidy caused by 4R-Tau expression during brain development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27064065,

title = {Unconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection},

author = {Lamba Omar Sangaré and Tchilabalo Dilezitoko Alayi and Benoit Westermann and Agnes Hovasse and Fabien Sindikubwabo and Isabelle Callebaut and Elisabeth Werkmeister and Frank Lafont and Christian Slomianny and Mohamed-Ali Hakimi and Alain Van Dorsselaer and Christine Schaeffer-Reiss and Stanislas Tomavo},

doi = {10.1038/ncomms11191},

issn = {2041-1723},

year  = {2016},

date = {2016-04-01},

journal = {Nat Commun},

volume = {7},

pages = {11191},

abstract = {Membrane trafficking pathways play critical roles in Apicomplexa, a phylum of protozoan parasites that cause life-threatening diseases worldwide. Here we report the first retromer-trafficking interactome in Toxoplasma gondii. This retromer complex includes a trimer Vps35-Vps26-Vps29 core complex that serves as a hub for the endosome-like compartment and parasite-specific proteins. Conditional ablation of TgVps35 reveals that the retromer complex is crucial for the biogenesis of secretory organelles and for maintaining parasite morphology. We identify TgHP12 as a parasite-specific and retromer-associated protein with functions unrelated to secretory organelle formation. Furthermore, the major facilitator superfamily homologue named TgHP03, which is a multiple spanning and ligand transmembrane transporter, is maintained at the parasite membrane by retromer-mediated endocytic recycling. Thus, our findings highlight that both evolutionarily conserved and unconventional proteins act in concert in T. gondii by controlling retrograde transport that is essential for parasite integrity and host infection. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26620082,

title = {High potential of adhesion to biotic and abiotic surfaces by opportunistic Staphylococcus aureus strains isolated from orthodontic appliances},

author = {Abderrahmen Merghni and Mouna Ben Nejma and Ines Dallel and Samir Tobji and Adel Ben Amor and Sébastien Janel and Frank Lafont and Mahjoub Aouni and Maha Mastouri},

doi = {10.1016/j.micpath.2015.11.009},

issn = {1096-1208},

year  = {2016},

date = {2016-02-01},

journal = {Microb Pathog},

volume = {91},

pages = {61--67},

abstract = {Orthodontic and other oral appliances act as reservoir of opportunistic pathogens that can easily become resistant to antibiotics and cause systemic infections. The aim of this study was to investigate the ability of Staphylococcus aureus strains isolated from healthy patients with orthodontic appliances, to adhere to biotic (HeLa cells) and abiotic surfaces (polystyrene and dental alloy). Adhesive ability to polystyrene was tested by crystal violet staining and quantitative biofilm production on dental alloy surfaces was evaluated by MTT reduction assay. In addition, the presence of icaA and icaD genes was achieved by polymerase chain reaction (PCR). Qualitative biofilm production revealed that 70.6% of strains were slime producers. The metabolic activity of S. aureus biofilms on dental alloy surfaces was high and did not differ between tested strains. Moreover, all the isolates were adhesive to HeLa cells and 94% of them harbor icaA and icaD genes. Considerable adhesion and internalization capacity to the epithelial HeLa cells and strong biofilm production abilities together, with a high genotypic expression of icaA/icaD genes are an important equipment of S. aureus to colonize orthodontic appliances and eventually to disseminate towards other body areas.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27448494,

title = {Manipulation of host membranes by the bacterial pathogens Listeria, Francisella, Shigella and Yersinia},

author = {Javier Pizarro-Cerdá and Alain Charbit and Jost Enninga and Frank Lafont and Pascale Cossart},

doi = {10.1016/j.semcdb.2016.07.019},

issn = {1096-3634},

year  = {2016},

date = {2016-01-01},

journal = {Semin Cell Dev Biol},

volume = {60},

pages = {155--167},

abstract = {Bacterial pathogens display an impressive arsenal of molecular mechanisms that allow survival in diverse host niches. Subversion of plasma membrane and cytoskeletal functions are common themes associated to infection by both extracellular and intracellular pathogens. Moreover, intracellular pathogens modify the structure/stability of their membrane-bound compartments and escape degradation from phagocytic or autophagic pathways. Here, we review the manipulation of host membranes by Listeria monocytogenes, Francisella tularensis, Shigella flexneri and Yersinia spp. These four bacterial model pathogens exemplify generalized strategies as well as specific features observed during bacterial infection processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27046256,

title = {TRANSAUTOPHAGY: European network for multidisciplinary research and translation of autophagy knowledge},

author = {Caty Casas and Patrice Codogno and Marcello Pinti and Henri Batoko and María Morán and Tassula Proikas-Cezanne and Fulvio Reggiori and Agnieszka Sirko and María S Soengas and Guillermo Velasco and Frank Lafont and Jon Lane and Mathias Faure and Andrea Cossarizza},

doi = {10.1080/15548627.2016.1140294},

issn = {1554-8635},

year  = {2016},

date = {2016-01-01},

journal = {Autophagy},

volume = {12},

number = {3},

pages = {614--617},

abstract = {A collaborative consortium, named "TRANSAUTOPHAGY," has been created among European research groups, comprising more than 150 scientists from 21 countries studying diverse branches of basic and translational autophagy. The consortium was approved in the framework of the Horizon 2020 Program in November 2015 as a COST Action of the European Union (COST means: CO-operation in Science and Technology), and will be sponsored for 4 years. TRANSAUTOPHAGY will form an interdisciplinary platform for basic and translational researchers, enterprises and stakeholders of diverse disciplines (including nanotechnology, bioinformatics, physics, chemistry, biology and various medical disciplines). TRANSAUTOPHAGY will establish 5 different thematic working groups, formulated to cooperate in research projects, share ideas, and results through workshops, meetings and short term exchanges of personnel (among other initiatives). TRANSAUTOPHAGY aims to generate breakthrough multidisciplinary knowledge about autophagy regulation, and to boost translation of this knowledge into biomedical and biotechnological applications. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26055540,

title = {Assessment of adhesion, invasion and cytotoxicity potential of oral Staphylococcus aureus strains},

author = {Abderrahmen Merghni and Mouna Ben Nejma and Imen Helali and Hajer Hentati and Antonino Bongiovanni and Frank Lafont and Mahjoub Aouni and Maha Mastouri},

doi = {10.1016/j.micpath.2015.05.010},

issn = {1096-1208},

year  = {2015},

date = {2015-09-01},

journal = {Microb Pathog},

volume = {86},

pages = {1--9},

abstract = {The oral cavity is regarded as a relevant site for Staphylococcus aureus colonization. However, characterization of virulence mechanisms of oral S. aureus remains to be uncovered. In this study, twenty one S. aureus strains isolated from the oral cavity of Tunisian patients were screened for adherence, invasion and cytotoxicity against HeLa cells. In addition, the presence of adhesins (icaA, icaD, can, fnbA and fnbB) and α-hemolysin (hla) genes in each strain was achieved by polymerase chain reaction (PCR). Our finding revealed that oral S. aureus strains were able to adhere and invade epithelial cells, with variable degrees (P < 0.05). Moreover they exhibited either low (23.8%) or moderate (76.2%) cytotoxic effects. In addition 76.2% of strains were icaA and icaD positive and 90.5% harbor both the fnbA and the fnbB gene. While the cna gene was detected in 12 strains (57.2%). Furthermore, the hla gene encoding the α-toxin was found in 52.4% of the isolates. All these virulence factors give to S. aureus the right qualities to become a redoubtable pathogen associated to oral infections. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25916824,

title = {Interplay between troponin T phosphorylation and O-N-acetylglucosaminylation in ischaemic heart failure},

author = {Emilie Dubois-Deruy and Aude Belliard and Paul Mulder and Marion Bouvet and Caroline Smet-Nocca and Sébastien Janel and Frank Lafont and Olivia Beseme and Philippe Amouyel and Vincent Richard and Florence Pinet},

doi = {10.1093/cvr/cvv136},

issn = {1755-3245},

year  = {2015},

date = {2015-07-01},

journal = {Cardiovasc Res},

volume = {107},

number = {1},

pages = {56--65},

abstract = {AIMS: Previous studies have reported that decreased serine 208 phosphorylation of troponin T (TnTpSer208) is associated with ischaemic heart failure (HF), but the molecular mechanisms and functional consequences of these changes are unknown. The aim of this study was to characterize the balance between serine phosphorylation and O-N-acetylglucosaminylation (O-GlcNAcylation) of TnT in HF, its mechanisms, and the consequences of modulating these post-translational modifications.



METHODS AND RESULTS: Decreased TnTpSer208 levels in the left ventricles of HF male Wistar rats were associated with reduced expression of PKCε but not of other cardiac PKC isoforms. In both isolated perfused rat hearts and cultured neonatal cardiomyocytes, the PKCε inhibitor εV1-2 decreased TnTpSer208 and simultaneously decreased cardiac contraction in isolated hearts and beating amplitude in neonatal cardiomyocytes (measured by atomic force microscopy). Down-regulating PKCε by silencing RNA (siRNA) also reduced TnTpSer208 in these cardiomyocytes, and PKCε-/- mice had lower TnTpSer208 levels than the wild-type. In parallel, HF increased TnT O-GlcNAcylation via both increased O-GlcNAc transferase and decreased O-GlcNAcase activity. Increasing O-GlcNAcylation (via O-GlcNAcase inhibition with Thiamet G) decreased TnTpSer208 in isolated hearts, while reducing O-GlcNAcylation (O-GlcNAc transferase siRNA) increased TnTpSer208 in neonatal cardiomyocytes. Mass spectrometry and NMR analysis identified O-GlcNAcylation of TnT on Ser190.



CONCLUSION: These data demonstrate interplay between Ser208 phosphorylation and Ser190 O-GlcNAcylation of TnT in ischaemic HF, linked to decreased activity of both PKCε and O-GlcNAcase and increased O-GlcNAc transferase activity. Modulation of these post-translational modifications of TnT may be a new therapeutic strategy in HF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25667106,

title = {Structured illumination microscopy and correlative microscopy to study autophagy},

author = {Laure-Anne Ligeon and Nicolas Barois and Elisabeth Werkmeister and Antonino Bongiovanni and Frank Lafont},

doi = {10.1016/j.ymeth.2015.01.017},

issn = {1095-9130},

year  = {2015},

date = {2015-03-01},

journal = {Methods},

volume = {75},

pages = {61--68},

abstract = {Autophagy is a predominant eukaryotic mechanism for the engulfment of "portions" of cytoplasm allowing their degradation to recycle metabolites. The autophagy is ubiquitous among the life kingdom revealing the importance of this pathway that appears more complex than previously thought. Several reviews have already addressed how to monitor this pathway and have highlighted the existence of new routes such as the LC3-associated phagocytosis (LAP) and the non-canonical autophagy. The principal difference between autophagosomes and LAP vacuoles is that the former has two limiting membranes positives for LC3 whereas the latter has one. Herein, we propose to emphasize the use of correlative light electron microscopy (CLEM) to answer some autophagy's related questions. The structured illumination microscopy (SIM) relatively easy to implement allows to better observe the Atg proteins recruitment and localization during the autophagy process. While LC3 recruitment is performed using light microscopy the ultrastructural morphological analysis of LC3-vacuoles is ascertained by electron microscopy. Hence, these combined and correlated approaches allow to tackle the LAP vs. autophagosome issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25046114,

title = {Role of VAMP3 and VAMP7 in the commitment of Yersinia pseudotuberculosis to LC3-associated pathways involving single- or double-membrane vacuoles},

author = {Laure-Anne Ligeon and Kevin Moreau and Nicolas Barois and Antonino Bongiovanni and Delphine-Armelle Lacorre and Elisabeth Werkmeister and Véronique Proux-Gillardeaux and Thierry Galli and Frank Lafont},

doi = {10.4161/auto.29411},

issn = {1554-8635},

year  = {2014},

date = {2014-09-01},

journal = {Autophagy},

volume = {10},

number = {9},

pages = {1588--1602},

abstract = {Yersinia pseudotuberculosis can replicate inside macrophages by hijacking autophagy and blocking autophagosome acidification. In bone marrow-derived macrophages, the bacteria are mainly observed inside double-membrane vacuoles positive for LC3, a hallmark of autophagy. Here, we address the question of the membrane traffic during internalization of Yersinia investigating the role of vesicle- associated membrane proteins (VAMPs). First, we show that as in epithelial cells, Yersinia pseudotuberculosis replicates mainly in nonacidic LC3-positive vacuoles. Second, in these cells, we unexpectedly found that VAMP3 localizes preferentially to Yersinia-containing vacuoles (YCVs) with single membranes using correlative light-electron microscopy. Third, we reveal the precise kinetics of VAMP3 and VAMP7 association with YCVs positive for LC3. Fourth, we show that VAMP7 knockdown alters LC3's association with single-and multimembrane-YCVs. Finally, in uninfected epithelial cells stimulated for autophagy, VAMP3 overexpression and knockdown led respectively to a lower and higher number of double-membrane, LC3-positive vesicles. Hence, our results highlight the role that VAMPs play in selection of the pathways leading to generation of ultrastructurally different LC3 compartments and pave the way for determining the full set of docking and fusion proteins involved in Yersinia pseudotuberculosis' intravesicular life cycle. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24880614,

title = {Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization},

author = {Sandra C Bernard and Nandi Simpson and Olivier Join-Lambert and Christian Federici and Marie-Pierre Laran-Chich and Nawal Maïssa and Haniaa Bouzinba-Ségard and Philippe C Morand and Fabrice Chretien and Saïd Taouji and Eric Chevet and Sébastien Janel and Frank Lafont and Mathieu Coureuil and Audrey Segura and Florence Niedergang and Stefano Marullo and Pierre-Olivier Couraud and Xavier Nassif and Sandrine Bourdoulous},

doi = {10.1038/nm.3563},

issn = {1546-170X},

year  = {2014},

date = {2014-07-01},

journal = {Nat Med},

volume = {20},

number = {7},

pages = {725--731},

abstract = {Neisseria meningitidis is a cause of meningitis epidemics worldwide and of rapidly progressing fatal septic shock. A crucial step in the pathogenesis of invasive meningococcal infections is the adhesion of bloodborne meningococci to both peripheral and brain endothelia, leading to major vascular dysfunction. Initial adhesion of pathogenic strains to endothelial cells relies on meningococcal type IV pili, but the endothelial receptor for bacterial adhesion remains unknown. Here, we report that the immunoglobulin superfamily member CD147 (also called extracellular matrix metalloproteinase inducer (EMMPRIN) or Basigin) is a critical host receptor for the meningococcal pilus components PilE and PilV. Interfering with this interaction potently inhibited the primary attachment of meningococci to human endothelial cells in vitro and prevented colonization of vessels in human brain tissue explants ex vivo and in humanized mice in vivo. These findings establish the molecular events by which meningococci target human endothelia, and they open new perspectives for treatment and prevention of meningococcus-induced vascular dysfunctions. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25484092,

title = {Autophagy in osteoblasts is involved in mineralization and bone homeostasis},

author = {Marie Nollet and Sabine Santucci-Darmanin and Véronique Breuil and Rasha Al-Sahlanee and Chantal Cros and Majlinda Topi and David Momier and Michel Samson and Sophie Pagnotta and Laurence Cailleteau and Séverine Battaglia and Delphine Farlay and Romain Dacquin and Nicolas Barois and Pierre Jurdic and Georges Boivin and Dominique Heymann and Frank Lafont and Shi Shou Lu and David W Dempster and Georges F Carle and Valérie Pierrefite-Carle},

doi = {10.4161/auto.36182},

issn = {1554-8635},

year  = {2014},

date = {2014-01-01},

journal = {Autophagy},

volume = {10},

number = {11},

pages = {1965--1977},

abstract = {Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23652193,

title = {Pathogen-induced autophagy signaling in innate immunity},

author = {Mathias Faure and Frank Lafont},

doi = {10.1159/000350918},

issn = {1662-8128},

year  = {2013},

date = {2013-01-01},

journal = {J Innate Immun},

volume = {5},

number = {5},

pages = {456--470},

abstract = {Innate immunity induces rapid responses to fight invading pathogens. To eliminate intracellular bacteria or viruses, innate cellular responses lead to the production of nuclear factor-κB-dependent inflammatory cytokines, inflammasome activation, type I interferon synthesis, and/or eventually death of the infected cells. Autophagy emerged as another component of innate immunity, as it offers an immediate autonomous cell defense mechanism by degrading intracellular pathogens. In addition, autophagy participates in the regulation of immune and inflammatory cell responses. Instead of providing a comprehensive status of the art that has already been addressed elsewhere, we chose to highlight some recent issues brought up in the field. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23003307,

title = {Cellular dewetting: opening of macroapertures in endothelial cells},

author = {David Gonzalez-Rodriguez and Madhavi P Maddugoda and Caroline Stefani and Sebastien Janel and Frank Lafont and Damien Cuvelier and Emmanuel Lemichez and Françoise Brochard-Wyart},

doi = {10.1103/PhysRevLett.108.218105},

issn = {1079-7114},

year  = {2012},

date = {2012-05-01},

journal = {Phys Rev Lett},

volume = {108},

number = {21},

pages = {218105},

abstract = {Pathogenic bacteria can cross from blood vessels to host tissues by opening transendothelial cell macroapertures (TEMs). To induce TEM opening, bacteria intoxicate endothelial cells with proteins that disrupt the contractile cytoskeletal network. Cell membrane tension is no longer resisted by contractile fibers, leading to the opening of TEMs. Here we model the opening of TEMs as a new form of dewetting. While liquid dewetting is irreversible, we show that cellular dewetting is transient. Our model predicts the minimum radius for hole nucleation, the maximum TEM size, and the dynamics of TEM opening, in good agreement with experimental data. The physical model is then coupled with biological experimental data to reveal that the protein missing in metastasis (MIM) controls the line tension at the rim of the TEM and opposes its opening.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22100162,

title = {cAMP signaling by anthrax edema toxin induces transendothelial cell tunnels, which are resealed by MIM via Arp2/3-driven actin polymerization},

author = {Madhavi P Maddugoda and Caroline Stefani and David Gonzalez-Rodriguez and Juha Saarikangas and Stéphanie Torrino and Sebastien Janel and Patrick Munro and Anne Doye and François Prodon and Michel Aurrand-Lions and Pierre L Goossens and Frank Lafont and Patricia Bassereau and Pekka Lappalainen and Françoise Brochard and Emmanuel Lemichez},

doi = {10.1016/j.chom.2011.09.014},

issn = {1934-6069},

year  = {2011},

date = {2011-11-01},

journal = {Cell Host Microbe},

volume = {10},

number = {5},

pages = {464--474},

abstract = {RhoA-inhibitory bacterial toxins, such as Staphylococcus aureus EDIN toxin, induce large transendothelial cell macroaperture (TEM) tunnels that rupture the host endothelium barrier and promote bacterial dissemination. Host cells repair these tunnels by extending actin-rich membrane waves from the TEM edges. We reveal that cyclic-AMP signaling produced by Bacillus anthracis edema toxin (ET) also induces TEM formation, which correlates with increased vascular permeability. We show that ET-induced TEM formation resembles liquid dewetting, a physical process of nucleation and growth of holes within a thin liquid film. We also identify the cellular mechanisms of tunnel closure and reveal that the I-BAR domain protein Missing in Metastasis (MIM) senses de novo membrane curvature generated by the TEM, accumulates at the TEM edge, and triggers Arp2/3-dependent actin polymerization, which induces actin-rich membrane waves that close the TEM. Thus, the balance between ET-induced TEM formation and resealing likely determines the integrity of the host endothelium barrier.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21740497,

title = {Ubiquitylation and autophagy in the control of bacterial infections and related inflammatory responses},

author = {Laure-Anne Ligeon and Nassima Temime-Smaali and Frank Lafont},

doi = {10.1111/j.1462-5822.2011.01628.x},

issn = {1462-5822},

year  = {2011},

date = {2011-09-01},

journal = {Cell Microbiol},

volume = {13},

number = {9},

pages = {1303--1311},

abstract = {The ubiquitin proteasome system and autophagy constitute key signalling pathways in the host response to infection. The identification of adaptors linking the two pathways has prompted a re-examination of the latter's involvement in inflammatory reactions and the clearance of bacteria. The ubiquitin-autophagy pathway is a preferred target for effectors from pathogens that seek to exploit and evade the host defence mechanisms. A number of new players and signalling nodes have recently been identified. Here, we discuss these new insights into the host's control of bacterial infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21504731,

title = {A role for septins in the interaction between the Listeria monocytogenes INVASION PROTEIN InlB and the Met receptor},

author = {Serge Mostowy and Sébastien Janel and Claire Forestier and Charles Roduit and Sandor Kasas and Javier Pizarro-Cerdá and Pascale Cossart and Frank Lafont},

doi = {10.1016/j.bpj.2011.02.040},

issn = {1542-0086},

year  = {2011},

date = {2011-04-01},

journal = {Biophys J},

volume = {100},

number = {8},

pages = {1949--1959},

abstract = {Septins are conserved GTPases that form filaments and are required for cell division. During interphase, septin filaments associate with cellular membrane and cytoskeleton networks, yet the functional significance of these associations have, to our knowledge, remained unknown. We recently discovered that different septins, SEPT2 and SEPT11, regulate the InlB-mediated entry of Listeria monocytogenes into host cells. Here we address the role of SEPT2 and SEPT11 in the InlB-Met interactions underlying Listeria invasion to explore how septins modulate surface receptor function. We observed that differences in InlB-mediated Listeria entry correlated with differences in Met surface expression caused by septin depletion. Using atomic force microscopy on living cells, we show that septin depletion significantly reduced the unbinding force of InlB-Met interaction and the viscosity of membrane tethers at locations where the InlB-Met interaction occurs. Strikingly, the same order of difference was observed for cells in which the actin cytoskeleton was disrupted. Consistent with a proposed role of septins in association with the actin cytoskeleton, we show that cell elasticity is decreased upon septin or actin inactivation. Septins are therefore likely to participate in anchorage of the Met receptor to the actin cytoskeleton, and represent a critical determinant in surface receptor function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22205992,

title = {Clag9 is not essential for PfEMP1 surface expression in non-cytoadherent Plasmodium falciparum parasites with a chromosome 9 deletion},

author = {Adéla Nacer and Emeric Roux and Sébastien Pomel and Christine Scheidig-Benatar and Hiroshi Sakamoto and Frank Lafont and Artur Scherf and Denise Mattei},

doi = {10.1371/journal.pone.0029039},

issn = {1932-6203},

year  = {2011},

date = {2011-01-01},

journal = {PLoS One},

volume = {6},

number = {12},

pages = {e29039},

abstract = {BACKGROUND: The expression of the clonally variant virulence factor PfEMP1 mediates the sequestration of Plasmodium falciparum infected erythrocytes in the host vasculature and contributes to chronic infection. Non-cytoadherent parasites with a chromosome 9 deletion lack clag9, a gene linked to cytoadhesion in previous studies. Here we present new clag9 data that challenge this view and show that surface the non-cytoadherence phenotype is linked to the expression of a non-functional PfEMP1.



METHODOLOGY/PRINCIPAL FINDINGS: Loss of adhesion in P. falciparum D10, a parasite line with a large chromosome 9 deletion, was investigated. Surface iodination analysis of non-cytoadherent D10 parasites and COS-7 surface expression of the CD36-binding PfEMP1 CIDR1α domain were performed and showed that these parasites express an unusual trypsin-resistant, non-functional PfEMP1 at the erythrocyte surface. However, the CIDR1α domain of this var gene expressed in COS-7 cells showed strong binding to CD36. Atomic Force Microscopy showed a slightly modified D10 knob morphology compared to adherent parasites. Trafficking of PfEMP1 and KAHRP remained functional in D10. We link the non-cytoadherence phenotype to a chromosome 9 breakage and healing event resulting in the loss of 25 subtelomeric genes including clag9. In contrast to previous studies, knockout of the clag9 gene from 3D7 did not interfere with parasite adhesion to CD36.



CONCLUSIONS/SIGNIFICANCE: Our data show the surface expression of non-functional PfEMP1 in D10 strongly indicating that genes other than clag9 deleted from chromosome 9 are involved in this virulence process possibly via post-translational modifications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21077843,

title = {How ubiquitination and autophagy participate in the regulation of the cell response to bacterial infection},

author = {Nicolas Dupont and Nassima Temime-Smaali and Frank Lafont},

doi = {10.1042/BC20100101},

issn = {1768-322X},

year  = {2010},

date = {2010-12-01},

journal = {Biol Cell},

volume = {102},

number = {12},

pages = {621--634},

abstract = {Bacterial infection relies on the micro-organism's ability to orchestrate the host's cell signalling such that the immune response is not activated. Conversely, the host cell has dedicated signalling pathways for coping with intrusions by pathogens. The autophagy of foreign micro-organisms (known as xenophagy) has emerged as one of the most powerful of these pathways, although the triggering mode remains largely unknown. In the present paper, we discuss the role that certain post-translational modifications (primarily ubiquitination) may play in the activation of xenophagy and how some bacteria have evolved mechanisms to subvert or hijack this process. In particular, we address the role played by P62/SQSTM1 (sequestosome 1). Finally, we discuss how autophagy can be subverted to eliminate bacteria-induced danger signals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20709289,

title = {Autophagy employs a new DAGger against bacteria},

author = {Frank Lafont},

doi = {10.1016/j.chom.2010.07.009},

issn = {1934-6069},

year  = {2010},

date = {2010-08-01},

journal = {Cell Host Microbe},

volume = {8},

number = {2},

pages = {129--130},

abstract = {Autophagy can orchestrate innate immune responses to bacterial infection by targeting invading pathogens for lysosomal degradation. In this issue of Cell Host & Microbe, Shahnazari et al. (2010) unveil the role played by the diacylglycerol-PKC pathway in the routing of intracellular Salmonella to autophagy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20180800,

title = {Autophagosomes can support Yersinia pseudotuberculosis replication in macrophages},

author = {Kevin Moreau and Sandra Lacas-Gervais and Naonobu Fujita and Florent Sebbane and Tamotsu Yoshimori and Michel Simonet and Frank Lafont},

doi = {10.1111/j.1462-5822.2010.01456.x},

issn = {1462-5822},

year  = {2010},

date = {2010-08-01},

journal = {Cell Microbiol},

volume = {12},

number = {8},

pages = {1108--1123},

abstract = {Yersinia pseudotuberculosis is able to replicate inside macrophages. However, the intracellular trafficking of the pathogen after its entry into the macrophage remains poorly understood. Using in vitro infected bone marrow-derived macrophages, we show that Y. pseudotuberculosis activates the autophagy pathway. Host cell autophagosomes subverted by bacteria do not become acidified and sustain bacteria replication. Moreover, we report that autophagy inhibition correlated with bacterial trafficking inside an acidic compartment. This study indicates that Y. pseudotuberculosis hijacks the autophagy pathway for its replication and also opens up new opportunities for deciphering the molecular basis of the host cell signalling response to intracellular Yersinia infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19951367,

title = {Galectin-3, a marker for vacuole lysis by invasive pathogens},

author = {Irit Paz and Martin Sachse and Nicolas Dupont and Joelle Mounier and Cecilia Cederfur and Jost Enninga and Hakon Leffler and Francoise Poirier and Marie-Christine Prevost and Frank Lafont and Philippe Sansonetti},

doi = {10.1111/j.1462-5822.2009.01415.x},

issn = {1462-5822},

year  = {2010},

date = {2010-04-01},

journal = {Cell Microbiol},

volume = {12},

number = {4},

pages = {530--544},

abstract = {Shigella bacteria invade macrophages and epithelial cells and following internalization lyse the phagosome and escape to the cytoplasm. Galectin-3, an abundant protein in macrophages and epithelial cells, belongs to a family of beta-galactoside-binding proteins, the galectins, with many proposed functions in immune response, development, differentiation, cancer and infection. Galectins are synthesized as cytosolic proteins and following non-classical secretion bind extracellular beta-galactosides. Here we analysed the localization of galectin-3 following entry of Shigella into the cytosol and detected a striking phenomenon. Very shortly after bacterial invasion, intracellular galectin-3 accumulated in structures in vicinity to internalized bacteria. By using immuno-electron microscopy analysis we identified galectin-3 in membranes localized in the phagosome and in tubules and vesicles that derive from the endocytic pathway. We also demonstrated that the binding of galectin-3 to host N-acetyllactosamine-containing glycans, was required for forming the structures. Accumulation of the structures was a type three secretion system-dependent process. More specifically, existence of structures was strictly dependent upon lysis of the phagocytic vacuole and could be shown also by Gram-positive Listeria and Salmonella sifA mutant. We suggest that galectin-3-containing structures may serve as a potential novel tool to spot vacuole lysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19829050,

title = {How autophagy regulates the host cell signaling associated with the postpartum bacteria cocoon experienced as a danger signal},

author = {Nicolas Dupont and Frank Lafont},

doi = {10.4161/auto.5.8.10218},

issn = {1554-8635},

year  = {2009},

date = {2009-11-01},

journal = {Autophagy},

volume = {5},

number = {8},

pages = {1222--1223},

abstract = {Shigella, the causative agent of human bacillary dysentery, invades the host cell, rapidly breaking the phagosome and multiplying in the cytosol. Here, we summarize our recent work showing the targeting of the leftover membrane remnants to autophagy together with trapped membrane-associated signaling molecules recruited during the immediate early entry step. We suggest that this mechanism participates in the bacteria-dependent orchestration of the cell response. Moreover, we propose that this signaling node may have relevance as to how the cell interprets endomembrane damage triggered by other stimuli.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19683680,

title = {Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy},

author = {Nicolas Dupont and Sandra Lacas-Gervais and Julie Bertout and Irit Paz and Barbara Freche and Guy Tran Van Nhieu and F Gisou van der Goot and Philippe J Sansonetti and Frank Lafont},

doi = {10.1016/j.chom.2009.07.005},

issn = {1934-6069},

year  = {2009},

date = {2009-08-01},

journal = {Cell Host Microbe},

volume = {6},

number = {2},

pages = {137--149},

abstract = {Intracellular pathogens like Shigella flexneri enter host cells by phagocytosis. Once inside, the pathogen breaks the vacuolar membrane for cytosolic access. The fate and function of the vacuolar membrane remnants are not clear. Examining Shigella-infected nonmyeloid cells, we observed that proteins associated with vacuolar membrane remnants are polyubiquinated, recruit the autophagy marker LC3 and adaptor p62, and are targeted to autophagic degradation. Further, inflammasome components and caspase-1 were localized to these membranes and correlated with dampened inflammatory response and necrotic cell death. In Atg4B mutant cells in which autophagosome maturation is blocked, polyubiquitinated proteins and P62 accumulated on membrane remnants, and as in autophagy-deficient Atg5(-/-) cells, the early inflammatory and cytokine response was exacerbated. Our results suggest that host membranes, after rupture by an invading cytoplasm-targeted bacterium, contribute to the cellular responses to infection by acting as a signaling node, with autophagy playing a central role in regulating these responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19619482,

title = {Stiffness tomography by atomic force microscopy},

author = {Charles Roduit and Serguei Sekatski and Giovanni Dietler and Stefan Catsicas and Frank Lafont and Sandor Kasas},

doi = {10.1016/j.bpj.2009.05.010},

issn = {1542-0086},

year  = {2009},

date = {2009-07-01},

journal = {Biophys J},

volume = {97},

number = {2},

pages = {674--677},

abstract = {The atomic force microscope is a convenient tool to probe living samples at the nanometric scale. Among its numerous capabilities, the instrument can be operated as a nano-indenter to gather information about the mechanical properties of the sample. In this operating mode, the deformation of the cantilever is displayed as a function of the indentation depth of the tip into the sample. Fitting this curve with different theoretical models permits us to estimate the Young's modulus of the sample at the indentation spot. We describe what to our knowledge is a new technique to process these curves to distinguish structures of different stiffness buried into the bulk of the sample. The working principle of this new imaging technique has been verified by finite element models and successfully applied to living cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19475637,

title = {Force spectroscopy of the interaction between mycobacterial adhesins and heparan sulphate proteoglycan receptors},

author = {Vincent Dupres and Claire Verbelen and Dominique Raze and Frank Lafont and Yves F Dufrêne},

doi = {10.1002/cphc.200900208},

issn = {1439-7641},

year  = {2009},

date = {2009-07-01},

journal = {Chemphyschem},

volume = {10},

number = {9-10},

pages = {1672--1675},

abstract = {Understanding the molecular interactions between bacterial adhesion proteins (adhesins) and their receptors is essential for elucidating the molecular mechanisms of bacterial pathogenesis. Here, atomic force microscopy (AFM) is used to explore the specific interactions between the heparin-binding hemagglutinin (HBHA) from Mycobacterium tuberculosis, and heparan sulphate proteoglycan (HSPG) receptors on live A549 pneumocytes. First, we show that the specific binding forces between single HBHA-HSPG pairs, 57+/-16 pN, are similar to the forces measured earlier between HBHA and heparin molecules. Second, we mapped the distribution of single HSPG receptors on the surface of A549 cells, revealing that the proteins are widely and homogeneously exposed. Third, we observed force curves with constant force plateaus at large pulling velocities, reflecting the extraction of membrane tethers or nanotubes. These single-molecule measurements provide new avenues in pathogenesis research, particularly for elucidating the molecular basis of pathogen-host interactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17981897,

title = {Elastic membrane heterogeneity of living cells revealed by stiff nanoscale membrane domains},

author = {Charles Roduit and F Gisou van der Goot and Paolo De Los Rios and Alexandre Yersin and Pascal Steiner and Giovanni Dietler and Stefan Catsicas and Frank Lafont and Sandor Kasas},

doi = {10.1529/biophysj.107.112862},

issn = {1542-0086},

year  = {2008},

date = {2008-02-01},

journal = {Biophys J},

volume = {94},

number = {4},

pages = {1521--1532},

abstract = {Many approaches have been developed to characterize the heterogeneity of membranes in living cells. In this study, the elastic properties of specific membrane domains in living cells are characterized by atomic force microscopy. Our data reveal the existence of heterogeneous nanometric scale domains with specific biophysical properties. We focused on glycosylphosphatidylinositol (GPI)-anchored proteins, which play an important role in membrane trafficking and cell signaling under both physiological and pathological conditions and which are known to partition preferentially into cholesterol-rich microdomains. We demonstrate that these GPI-anchored proteins reside within domains that are stiffer than the surrounding membrane. In contrast, membrane domains containing the transferrin receptor, which does not associate with cholesterol-rich regions, manifest no such feature. The heightened stiffness of GPI domains is consistent with existing data relating to the specific condensation of lipids and the slow diffusion rates of lipids and proteins therein. Our quantitative data may forge the way to unveiling the links that exist between membrane stiffness, molecular diffusion, and signaling activation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17400692,

title = {Elastic properties of the cell surface and trafficking of single AMPA receptors in living hippocampal neurons},

author = {Alexandre Yersin and Harald Hirling and Sandor Kasas and Charles Roduit and Karina Kulangara and Giovanni Dietler and Frank Lafont and Stefan Catsicas and Pascal Steiner},

doi = {10.1529/biophysj.106.092742},

issn = {0006-3495},

year  = {2007},

date = {2007-06-01},

journal = {Biophys J},

volume = {92},

number = {12},

pages = {4482--4489},

abstract = {Although various approaches are routinely used to study receptor trafficking, a technology that allows for visualizing trafficking of single receptors at the surface of living cells remains lacking. Here we used atomic force microscope to simultaneously probe the topography of living cells, record the elastic properties of their surface, and examine the distribution of transfected alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)-type glutamate receptors (AMPAR). On nonstimulated neurons, AMPARs were located in stiff nanodomains with high elasticity modulus relative to the remaining cell surface. Receptor stimulation with N-methyl-D-aspartate (NMDA) provoked a permanent disappearance of these stiff nanodomains followed by a decrease (53%) of the number of surface AMPARs. Blocking electrical activity before NMDA stimulation recruited the same number of AMPARs for internalization, preceded by the loss of the stiff nanodomains. However, in that case, the stiff nanodomains were recovered and AMPARs were reinserted into the membrane shortly after. Our results show that modulation of receptor distribution is accompanied by changes in the local elastic properties of cell membrane. We postulate, therefore, that the mechanical environment of a receptor might be critical to determine its specific distribution behavior in response to different stimuli.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17279635,

title = {Preparation of superhydrophobic silicon oxide nanowire surfaces},

author = {Yannick Coffinier and Sébastien Janel and Ahmed Addad and Ralf Blossey and Léon Gengembre and Edmond Payen and Rabah Boukherroub},

doi = {10.1021/la063345p},

issn = {0743-7463},

year  = {2007},

date = {2007-02-01},

journal = {Langmuir},

volume = {23},

number = {4},

pages = {1608--1611},

abstract = {The paper reports on the preparation of superhydrophobic amorphous silicon oxide nanowires (a-SiONWs) on silicon substrates with a contact angle greater than 150 degrees by means of surface roughness and self-assembly. Nanowires with an average mean diameter in the range 20-150 nm and 15-20 microm in length were obtained by the so-called solid-liquid-solid (SLS) technique. The porous nature and the high roughness of the resulting surfaces were confirmed by AFM imaging. The superhydrophobicity resulted from the combined effects of surface roughness and chemical modification with fluorodecyl trichlorosilane.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17129051,

title = {Stability of the gold/silica thin film interface: electrochemical and surface plasmon resonance studies},

author = {Sabine Szunerits and Yannick Coffinier and Sébastien Janel and Rabah Boukherroub},

doi = {10.1021/la060793o},

issn = {0743-7463},

year  = {2006},

date = {2006-12-01},

journal = {Langmuir},

volume = {22},

number = {25},

pages = {10716--10722},

abstract = {This article reports chemical stability studies of a gold film electrode coated with thin silicon oxide (SiOx) layers using electrochemical, surface plasmon resonance (SPR) and atomic force microscopy (AFM) techniques. Silica films with different thicknesses (d = 6.4, 9.7, 14.5, and 18.5 nm) were deposited using a plasma-enhanced chemical vapor deposition technique (PECVD). For SiOx films with d >/= 18.5 nm, the electrochemical behavior is characteristic of a highly efficient barrier for a redox probe. SiOx films with thicknesses between 9.5 and 14.5 nm were found to be less efficient barriers for electron transfer. The Au/SiOx interface with 6.4 nm of SiOx, however, showed an enhanced steady-state current compared to that of the other films. The stability of this interface in solutions of different pH was investigated. Whereas a strongly basic solution led to a continuous dissolution of the SiOx interface, acidic treatment produced a more reticulated SiOx film and improved electrochemical behavior. The electrochemical results were corroborated by SPR measurements in real time and AFM studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15839890,

title = {Bacterial invasion via lipid rafts},

author = {Frank Lafont and F Gisou van der Goot},

doi = {10.1111/j.1462-5822.2005.00515.x},

issn = {1462-5814},

year  = {2005},

date = {2005-05-01},

journal = {Cell Microbiol},

volume = {7},

number = {5},

pages = {613--620},

abstract = {Accumulating reports document the use by pathogens of cholesterol-enriched lipid microdomains, often called lipid rafts, as cell surface platforms to interact, bind and possibly enter into host cells. The challenge is now to understand what could be the functional role of these domains during pathogen invasion. Are they hijacked as general clustering devices for cellular binding sites and/or do they have other roles? In particular, is their cell signalling capacity activated and used by pathogens? In reverse, could lipid rafts activate bacterial mechanisms required for invasion? These issues will be discussed after an introduction on the current view on lipid rafts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15819615,

title = {Oiling the key hole},

author = {Frank Lafont and F Gisou van der Goot},

doi = {10.1111/j.1365-2958.2005.04570.x},

issn = {0950-382X},

year  = {2005},

date = {2005-05-01},

journal = {Mol Microbiol},

volume = {56},

number = {3},

pages = {575--577},

abstract = {Many bacteria have been found to interact with specialized domains, rich in cholesterol and sphingolipids, of the host plasma membrane, termed lipid rafts. The mechanisms that underlie this interaction are starting to be unravelled. In this issue, Hayward et al. show that early effector proteins secreted by type III secretion harbouring Gram-negative bacteria are in fact cholesterol-binding proteins. Combined with other recent findings, this work shows that multiple steps leading to infection by these bacteria depend on raft components: activation of secretion, binding, perforation of the host cell membrane and signalling to trigger bacterial engulfment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15364928,

title = {Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism},

author = {Françoise G van der Goot and Guy Tran van Nhieu and Abdelmounaaïm Allaoui and Phillipe Sansonetti and Frank Lafont},

doi = {10.1074/jbc.M406824200},

issn = {0021-9258},

year  = {2004},

date = {2004-11-01},

journal = {J Biol Chem},

volume = {279},

number = {46},

pages = {47792--47798},

abstract = {Infection by the Gram-negative bacterial pathogen Shigella flexneri depends on its ability to invade host cells. Bacterial engulfment requires a functional type III secretion system (TTSS) allowing the translocation into host cells of bacterial effectors that activate cell-signaling cascades. We demonstrated previously that specialized lipid membrane domains enriched in cholesterol and sphingolipids (rafts) are involved during early steps of invasion, namely in binding and host cell entry. In this study, we addressed the issue of contact-mediated secretion by the TTSS. We show that contact-mediated and TTSS-induced hemolysis depend on the presence of cholesterol on the host cell surface. We found that purified detergent resistant membranes were able to activate TTSS. Finally, we found that artificial liposomes, devoid of proteins, were able to activate the TTSS but only when their composition mimicked that of lipid rafts. Altogether, these data indicate that specific lipid packing can trigger contact-mediated secretion by S. flexneri.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15036133,

title = {Bacterial subversion of lipid rafts},

author = {Frank Lafont and Laurence Abrami and F Gisou van der Goot},

doi = {10.1016/j.mib.2003.12.007},

issn = {1369-5274},

year  = {2004},

date = {2004-02-01},

journal = {Curr Opin Microbiol},

volume = {7},

number = {1},

pages = {4--10},

abstract = {Bacteria rely on numerous basic cellular functions of their target cells to reach successful infection. The recent discovery that the plasma membrane contains specialized microdomains, called lipid rafts, with many specific functions but in particular with the ability to concentrate signaling molecules, has therefore attracted the attention of cellular microbiologists. Since then an increasing number of bacteria and their products have been shown to interact with lipid rafts to promote infection or intoxication. Here we review why certain bacteria and/or their products are attracted toward these lipid microdomains.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12198147,

title = {Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction},

author = {Frank Lafont and Guy Tran Van Nhieu and Kentaro Hanada and Philippe Sansonetti and F Gisou van der Goot},

doi = {10.1093/emboj/cdf457},

issn = {0261-4189},

year  = {2002},

date = {2002-09-01},

journal = {EMBO J},

volume = {21},

number = {17},

pages = {4449--4457},

abstract = {Shigellosis is an acute inflammatory bowel disease caused by the enteroinvasive bacterium SHIGELLA: Upon host cell-Shigella interaction, major host cell signalling responses are activated. Deciphering the initial molecular events is crucial to understanding the infectious process. We identified a molecular complex involving proteins of both the host, CD44 the hyaluronan receptor, and Shigella, the invasin IpaB, which partitions during infection within specialized membrane microdomains enriched in cholesterol and sphingolipids, called rafts. We also document accumulation of cholesterol and raft-associated proteins at Shigella entry foci. Moreover, we report that Shigella entry is impaired after cholesterol depletion using methyl-beta-cyclodextrin. Finally, we find that Shigella is less invasive in sphingosid-based lipid-deficient cell lines, demonstrating the involvement of sphingolipids. Our results show that rafts are implicated in Shigella binding and entry, suggesting that raft-associated molecular machineries are engaged in mediating the cell signalling response required for the invasion process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}