A selection of the most significant contributions of the group (original articles and reviews) with annotation

Functional genomics of Lactobacillus casei establishment in the gut.

Licandro-Seraut H, Scornec H, Pédron T, Cavin JF, Sansonetti PJ.

Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):E3101-9. doi: 10.1073/pnas.1411883111. Epub 2014 Jul 14.

PMID:25024222

 

The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration.

Nigro G, Rossi R, Commere PH, Jay P, Sansonetti PJ.

Cell Host Microbe. 2014 Jun 11;15(6):792-8. doi: 10.1016/j.chom.2014.05.003. Epub 2014 May 29.

PMID:24882705

 

B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection.

Nothelfer K, Arena ET, Pinaud L, Neunlist M, Mozeleski B, Belotserkovsky I, Parsot C, Dinadayala P, Burger-Kentischer A, Raqib R, Sansonetti PJ, Phalipon A.

J Exp Med. 2014 Jun 2;211(6):1215-29. doi: 10.1084/jem.20130914. Epub 2014 May 26.

PMID:24863068

 

 

ZapE is a novel cell division protein interacting with FtsZ and modulating the Z-ring dynamics.

Marteyn BS, Karimova G, Fenton AK, Gazi AD, West N, Touqui L, Prevost MC, Betton JM, Poyraz O, Ladant D, Gerdes K, Sansonetti PJ, Tang CM.

MBio. 2014 Mar 4;5(2):e00022-14. doi: 10.1128/mBio.00022-14.

PMID:24595368

 

CAMPBELL-VALOIS, FX., SCHNUPF, P., NIGRO, G., SACHSE, M., SANSONETTI, PJ., PARSOT, C. A fluorescent reporter reveals On/Off régulation of the Shigella Type III sécrétion apparatus during entry and cell-to-cell spread. Cell Host Microbe. 2014 Feb 12 ; 15(2) :177-189.

First reporter system to allow following in real time the On/Off state of a type III secretory apparatus at the different stages of interaction between an invasive bacterium and its target cell.

 

PUHAR, A., TRONCHERE, H., PAYRASTRE, B., NHIEU, GT., SANSONETTI, PJ. A Shigella effector dampens inflammation by regulating epithelial release of danger signal ATP through production of the lipid mediator Ptdlns5P. Immunity. 2013 Dec 12 ; 39(6) :1121-1131.

Blocking emission of epithelial danger signal ATP as part of the pathogenic strategy of Shigella.

 

SALGADO-PABON, W., Celli, S., ARENA, ET., NOTHELFER, K., ROUX, P., SELLGE, G., FRIGIMELICA, E., BOUSSO, P., SANSONETTI, PJ., PHALIPO N, A. Shigella impairs T lymphocyte dynamics in vivo. Proc. Nat. Acad. Sci. (USA). 2013. Mar 19 ; 110 (12) :4458-4463.

Two-photon microscopy reveals alteration of T cell trajectories in lymph node in the course of Shigella infection.

 

MOUNIER, J., BONCOMPAIN, G., SENEROVIC, L., LAGACHE, T., CHRETIEN, F., PEREZ, F., KOLBE, M., OLIVO-MARIN, JC., SANSONETTI, PJ., SAUVONNET, N. Shigella effector IpaB-induced cholesterol relocation disrupts the Golgi complex and recycling network to inhibit host cell secretion. Cell Host Microbe. 2012. Sept 13 ; 12(3)381-389.

Subversion of epithelial cell polarity and secretory capacities : a novel angle of Shigella pathogenesis.

 

PEDRON, T., MULET, C., DAUGA, C., FRANGEUL, L., CHERVAUX, C., GROMPONE, G., SANSONETTI, PJ. A Crypt Specific Core Microbiota resides in the mouse colon. mBio. 2012 May 22;3(3). pii: e00116

First demonstration that a restricted aerobic microbiota inhabits the colonic crypt of mice. Essential discovery to establish the premises of studies analyzing how the microbiota affects colonic crypt homeostasis.

 

BERGOUNIOUX, J., ELISEE, R., PRUNIER, AL., DONNADIEU, F., SPERANDIO, B., SANSONETTI, PJ., ARBIBE, L. Calpain activation by the Shigella flexneri Effector VirA regulates key steps in the formation and life of the bacterium’s epithelial niche. Cell Host Microbe. 2012 Mar 15;11(3):240-252

New opening in the study of Shigella intracellular life style, particularly how the bacteria manipulate the degradation of p53.

 

KONRADT C, FRIGIMELICA E, NOTHELFER K, PUHAR A, SALGADO-PABON W, DI BARTOLO V, SCOTT-ALGARA D, RODRIGUES CD, SANSONETTI PJ , PHALIPON A.

The Shigella flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism. Cell Host Microbe. 2011 Apr 21;9(4):263-72

First demonstration that an invasive bacterial pathogen engages activated T lymphocytes and alter their motility by blocking their capacity to respond to a chemoattractive gradient. Ongoing confirmation in vivo by 2-photon microscopy. Essential step in understanding how Shigella dampens the adaptive immune response.

 

ROMERO S, GROMPONE G, CARAYOL N, MOUNIER J, GUADAGNINI S, PREVOST MC, SANSONETTI PJ,  TRAN VAN NHIEU G. ATP-Mediated Erk1/2 Activation Stimulates Bacterial Capture by Filopodia, which Precedes Shigella Invasion of Epithelial Cells. Cell Host Microbe. 2011 Jun 16;9(6):508-19

An original strategy developed by cells to capture environmental objects in their extracellular milieu. Original strategy for Shigella to capitalize on this system and manipulate it to enhance its capture by cells.

 

MARTEYN B, WEST NP, BROWNING DF, COLE JA, SHAW JG, PALM F, MOUNIER J, PREVOST MC, SANSONETTI PJ*, TANG CM*. Modulation of Shigella  virulence in response to available oxygen in vivo. Nature. 2010 May 20;465(7296):355-8 (* co-corresponding authors)

This article illuminates a novel aspect of the virulence regulation of Shigella at the mucosal surface. It shows the importance of oxygen to activate the state of secretory competence of the TypeIII secretory system and at the same time demonstrates the presence of oxygen at epithelial surface in the gut lumen.

 

PAZ I, SACHSE M, DUPONT N, MOUNIER J, CEDERFUR C, ENNINGA J, LEFFLER H, POIRIER F, PREVOST MC, LAFONT F, SANSONETTI PJ. Galectin-3, a marker for vacuole lysis by invasive pathogens. Cell Microbiol. 2010 12(4) :530-544

Demonstration that Gal-3 selectively binds/decorates the membrane remnants issued from the lysis of Shigella endocytic vacuole. An essential tool now available to follow the kinetics of membrane lysis.

 

MOUNIER J, POPOFF MR, ENNINGA J, FRAME MC, SANSONETTI PJ , VAN NHIEU GT. The IpaC carboxyterminal effector domain mediates Src-dependent actin polymerization during Shigella invasion of epithelial cells. PLoS Pathog. 2009 Jan;5(1):e1000271

Demonstration and careful analysis of the segment of IpaC C-terminal sequence that activates src and causes cortactin dependant nucleation of actin in the course of Shigella entry.

 

DUPONT N, LACAS-GERVAIS S, BERTOUT J, PAZ I, FRECHE B, VAN NHIEU GT, VAN DER GOOT FG, SANSONETTI PJ, LAFONT F. Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy. Cell Host Microbe. 2009 Aug 20;6(2):137-49

First demonstration that pro-inflammatory signaling by invasive bacteria occurs early, thanks to the formation of a signaling platform at the level of membrane remnants issued from lysis of endocytic vacuole. Membrane remnants are captured and degraded by autophagy, thus down-regulating inflammation signals.

 

SPERANDIO B, REGNAULT B, GUO J, ZHANG Z, STANLEY SL JR, SANSONETTI PJ* , PEDRON T. 2008 Virulent Shigella flexneri  subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. J Exp Med. 2008 May 12;205(5):1121-32 (* corresponding author)

First molecular analysis and identification of the effectors that cause dampening of antimicrobial peptide expression in the course of experimental shigellosis. An essential discovery to better understand how Shigella subverts the antimicrobial capacities of the intestinal epithelium to achieve efficient colonization.

 

JAUMOUILLE V, FRANCETIC O, SANSONETTI PJ, TRAN VAN NHIEU G. 2008 Cytoplasmic targeting of IpaC to the bacterial pole directs polar type III secretion in Shigella . EMBO J. 2008 Jan 23;27(2):447-57

Very unexpected discovery that initial secretion of entry effectors of Shigella via the TypeIII secretory apparatus is polar.

 

KUFER TA, KREMMER E, ADAM AC, PHILPOTT DJ, SANSONETTI PJ.  2008 The pattern-recognition molecule Nod1 is localized at the plasma membrane at sites of bacterial interaction. Cell Microbiol. 2008 Feb;10(2):477-86

Important observation that Nod molecules are located at the cell membrane where the microbial danger is first perceived by the cell.

 

ROHDE, J. R., BREITKREUTZ, A. CHENAL, A., SANSONETTI, P. J ., PARSOT, C. 2007 Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe, 1: 77-83

A breakthrough paper identifying the catalytic function of IpaH Shigella effectors as an E3 ligase.

 

ARBIBE L., KIM D.W., BATSCHE E., PEDRON T., MATEESCU B., MUCHARDT C., PARSOT C., SANSONETTI, P.J., 2007 An injected bacterial effector targets chromatin access for nuclear factor kappa B to alter transcription of host immune genes. Nature Immunology, 8(1):47-56

A breakthrough paper reporting the function of a “second wave” effector of Shigella. First evidence that such effector can alter inflammatory gene expression (ie: IL8) by epigenetic modulation of chromatin constraint involving dephosphorymation of MAPKinases and histone H3.

 

PENDARIES C, TRONCHERE H, ARBIBE L, MOUNIER J, GOZANI O, CANTLEY L, FRY MJ, GAITS-IACOVONI F, SANSONETTI PJ,  PAYRASTRE B, 2006 PtdIns(5)P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri  infection. EMBO J, 25(5) : 1024-1034

Another essential function of IpgD : activation of PI3K and extension of Shigella host cell life span.

 

TOURNEBIZE R., DOAN B-T., DILLIES M-A., MAURIN S., BELOEIL J-C., SANSONETTI P.J ., 2006 Magnetic Resonance Imaging of Klebsiella pneumoniae  induced pneumonia in mice. Cell. Microbiol. 8:33-43

First analysis of the dynamics of an infectious process by NMR in the mouse lung.

 

ENNINGA, J., MOUNIER, J., SANSONETTI, P.J.,  TRAN VAN NHIEU, G. 2005. Studying the secretion of Type III effectors into host cells in real time. Nature Methods, 2(12) : 959-965

The first article to provide real time, dynamic imaging of effectors secretion by the TypeIII secretory apparatus of Shigella.

 

Parsot, C., Ageron, E., Penno, C., Mavris, M., Jamoussi, K., d’Hauteville, H., Sansonetti, P. and Demers, B. (2005), A secreted anti-activator, OspD1, and its chaperone, Spa15, are involved in the control of transcription by the type III secretion apparatus activity in Shigella flexneri. Molecular Microbiology, 56: 1627–1635.

 

KIM DW, LENZEN G, PAGE AL, LEGRAIN P, SANSONETTI PJ,  PARSOT C, 2005. The Shigella flexneri  effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc Natl Acad Sci U S A. 102(39):14046-51

First biochemical characterization of one of the “second wave” effectors injected through the type III secretory system which are involved in the subversion of the innate immune response.

 

WEST NP*, SANSONETTI PJ*,  MOUNIER J, EXLEY RM, PARSOT C, GUADAGNINI S, PREVOST MC, PROCHNICKACHALUFOUR A, DELEPIERRE M, TANGUY M, TANG CM, 2005. Optimization of virulence functions through glucosylation of Shigella  LPS. Science, 307: 1313-1317 (*co-first authors)

A striking example of the efficiency of “signature tagged mutagenesis” to identify genes unexpectedly essential for pathogenesis, as assayed in an in vivo model. Glucosylation of LPS O-side chains is essential to impose an helicoidal structure to these chains, thereby allowing reduction of their length, facilitating the interaction of the type III secretory apparatus with cells, without altering resistance to innate immune defenses.

 

BOUGNERES L, GIRARDIN SE, WEED SA, KARGINOV AV, OLIVO-MARIN JC, PARSONS JT, SANSONETTI PJ , VAN NHIEU GT., 2004 Cortactin and Crk cooperate to trigger actin polymerization during Shigella  invasion of epithelial cells. J Cell Biol. 166(2):225-35

Important discovery regarding the signaling of Shigella entry. In accordance with Dehio et al., 1995, this paper demonstrates the essential role of cortactin in elicitin actin nucleation and polymerization of actin upon Shigella entry. Suggests the dominant role of src in the process.

 

PEDRON, T., THIBAULT, C., SANSONETTI, P.J., 2003 The invasive phenotype of Shigella flexneri  directs a distinct gene expression pattern in the human intestinal epithelial cell line Caco-2. J. Biol. Chem., 278(36):33878-33886

One of the first articles analyzing the global transcriptional profile of intestinal cells infected by an enteroinvasive microorganism, with a non invasive mutant used as control. This work was pioneer in realizing to which point Shigella was able to alter expression of proinflammatory genes.

 

GIRARDIN, S.E., TRAVASSOS, L.H., HERVÉ, M., BLANOT, D., BONECA, I.G., PHILPOTT, D.J., SANSONETTI, PJ., MENGIN-LECREULX, S., 2003 Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J. Biol. Chem., 278(43):41702-41708

Establishing the molecular bases for differential recognition of various peptidoglycan fragments by Nod molecules.

 

TRAN VAN NHIEU, G., CLAIR, C., BRUZZONE, R., MESNIL, M., SANSONETTI, P.J.,  COMBETTES, L. 2003 Connexin-dependent intercellular communication increases Shigella  invasion and dissemination in epithelial cells Nature Cell Biol, 5:720-726

The first demonstration of the role of connexins as components of hemi-channels causing paracrine signaling in the course of Shigella infection of epithelial cells.

 

FERNANDEZ MI, THUIZAT A, PEDRON T, NEUTRA M, PHALIPON A, SANSONETTI PJ., 2003 A newborn mouse model for the study of intestinal pathogenesis of shigellosis. Cell. Micro., 5:481-491

Description of the only reliable model of Shigella infection in the mouse.

 

FERNANDEZ MI, PEDRON T, TOURNEBIZE R, OLIVO-MARIN JC, SANSONETTI PJ , PHALIPON A, 2003 Anti-inflammatory role for intracellular dimeric immunoglobulin A by neutralization of lipopolysaccharide in epithelial cells. Immunity, 18:739-749

First demonstration that sIgAs, in the course of their transcytosis, can intercept bacterial LPS, and therby affect its proinflammatory signaling. This function is now acknowledged as one of the key functions of sIgA.

 

GIRARDIN SE, GOMPERTS-BONECA, I.,, CARNEIRO LAM, ANTIGNAC A, JÉHANNO M, VIALA J, TEDIN K, TAHA MH, LABIGNE A, ZÄHRINGER U, COYLE AJ, DISTEFANO PJ, BERTIN J, SANSONETTI PJ , PHILPOTT DJ, 2003 Nod1 detects specifically Gram-negative bacteria through GlcNAc-MurNAc tripeptide, a peptidoglycan motif. Science 300(5625):1584-1587

Demonstration that MTP is the agonist of Nod1. This and the following article established the molecular bases of innate intracellular sensing of bacteria (agonist & receptor).

 

GIRARDIN, S., GOMPERTS-BONECA, I., VIALA, J., LABIGNE, A., PHILPOTT, D.J., SANSONETTI, P.J., 2003. Nod2 is a general sensor of peptidoglycan through muramyldipeptide (MDP) detection.J. Biol. Chem., 278(11):8869-72.

My most cited article. Demonstration that MDP is the agonist of Nod2. The previous article and current article establishedthe molecular bases of innate intracellular sensing of bacteria (agonist & receptor).

 

CHAMAILLARD, M., PHILPOTT, D.J., GIRARDIN, S.E., ZOUALI, H., LESAGE, S., CHAREYRE,, F., HUNG BUI, T., GIOVANNINI, M., ZAEHRINGER, U., PENARD-LACRONIQUE, V., SANSONETTI, P.J.,  HUGOT, J.P., THOMAS, G., 2003 Gene-environment interactin modulated by allelic heterogeneity in inflammatory disease. PNAS, 100(6):3455-3460

First evidence that nod2 mutations identified in familial cases of Crohn’s Disease lead to a loss of function in activation of the pro-inflammatory signals in presence of MDP ligand.

 

NIEBUHR, K., GIURATO, S., PEDRON, T., PHILPOTT, D.J., GAITS, F., SABLE, J., SHEETZ, M.P., PARSOT, C., SANSONETTI, P.J.,  PAYRASTRE, B., 2002 Conversion of PrdIns(4,5)P2 into PtdIns(5)P by the S. flexneri  effector IpgD reorganizes host cell morphology. EMBO J., 21:5069-5078

Identification of the function of IpgD as a phosphatidyl-inositol phosphatase with specificity on phosphate radical in 4. This was a biochemical “tour de force” because until that point, PI4P and PI5P could not be separated and individually identified.

 

LAFONT, F., TRAN VAN NHIEU, G., HANADA, K., SANSONETTI, P.J.,  VAN DER GOOT, F.G., 2002 Initial steps of Shigella  infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction. EMBO J., 21:4449-4457

First evidence that cholesterol is essential to the productive interaction of the Shigella TypeIII secretion apparatus with eukaryotic cell membranes.

 

d'HAUTEVILLE, H., KHAN, S., MASKELL, D., KUSSAK, A., WEINTRAUB, A., MATHISON, J., ULEVITCH, R., WUSCHER, N., PARSOT, C., SANSONETTI, P.J.,  2002 Two msbB  genes encoding maximal acylation of lipid A are required for invasive Shigella flexneri  to mediate inflammatory rupture and destruction of the intestinal epithelium. J. Immunol., 168: 5240-5251

A genetic approach to study the actual impact of endotoxin acylation on pathogenesis.

 

GIRARDIN, S.E., TOURNEBIZE, R., MAVRIS, M., PAGE, A.L., LI, X., STARK, G.R., BERTIN, J., DISTEFANO, P.S., YANIV, M., SANSONETTI, P.J.,  PHILPOTT, D.J., 2001. CARD4/Nod1 mediates NF-kB and JNK activation by invasive Shigella flexneri. EMBO Reports 2:736-742

Another founding paper of Cellular Microbiology: demonstration of intracellular sensing of bacteria and identification of Nod molecules as sensors. Beginning of the “saga” of NLRs as intracellular danger sensors.

 

MAVRIS, M., PAGE, A.J., TOURNEBIZE, R., DEMERS, B., SANSONETTI, P.J.,  PARSOT, C., 2002 Regulation of transcription by the activity of the Shigella flexneri  type III secretion apparatus.

Mol. Microbiol., 43:1543-1553

A breackthrough paper that illuminated the regulation of expression of a “second wave” of Shigella plasmid virulence genes that are under control of the activation of the Type III secretory apparatus.

 

NIEBUHR, K, JOUIHRI, N, ALLAOUI, A, GOUNON, P, SANSONETTI, PJ , PARSOT C. , 2000

IpgD, a protein secreted by the type III secretion machinery of Shigella flexneri , is chaperoned by IpgE and implicated in entry focus formation. Mol Microbiol 38: 8-19

Dissection of the secretory process of the important metaeffector IpgD.

 

PHILPOTT DJ, YAMAOKA S, ISRAËL A, AND SANSONETTI PJ . 2000. Invasive Shigella flexneri  activates NF-kB through an LPS-dependent innate intracellular response and leads to IL-8 expression in epithelial cells. J Immunol 165:903-914

The paper that put us on the track of the existence of a dedicated sensing system of bacteria in the cell cytosolic compartment.

 

BUCHREISER C., GLASER P., RUSNIOK C., NEDJARI H., d'HAUTEVILLE H., KUNST F., SANSONETTI P., PARSOT C., 2000 The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri. Mol. Microbiol., 38(4):760-771

Sequence and annotation of the entire S. flexneri virulence plasmid.

 

SANSONETTI, P.J., PHALIPON, A., ARONDEL, J., THIRUMALAI, K., BANERJEE, S., AKIRA, S.,TAKEDA, K., ZYCHLINSKY, A., 2000 Caspase-1 activation of IL1b and IL-18 are essential for Shigella flexneri  induced inflammation. Immunity, 12(5):581-590

Ultimate demonstration of the role of IL-1beta and IL-18 in the pathogenesis of shigellosis. Supported the importance of pro-inflammatory apoptosis (pyroptosis) in inflammation and diffusion of infection.

 

BLOCKER, A., GOUNON, P., LARQUET, E., NIEBUHR, K., CABIAUX, V., PARSOT, C., SANSONETTI, P.J.,  1999 Role of Shigella ’s type III secretion system in insertion of IpaB and IpaC into the host membrane. J. Cell Biol., 147:683-693

First visualization and functional demonstration of Shigella type III secretion system.

 

KOTLOFF, K.L., WINICKOFF, J.P., IVANOFF, B., CLEMENS, J.D., SWERDLOW, D.L., SANSONETTI, P.J.,  ADAK, G.K., LEVINE, M.M., 1999. Global burden of Shigella  infections: implication for vaccine development and implementation. WHO Bulletin. 77 :651-666

This article which remains a land mark in the epidemiology of Shigella

 

PAGE, A.L., OHAYON, H., GOUNON, P., SANSONETTI, P.J . PARSOT, C., 1999 Role of IpaB and IpaC in the intercellular dissemination of Shigella flexneri. Cellular Microbiology, 1 :183-193

Clever molecular demonstration of the role of IpaB/C in cell to cell spread by constructing a mutant conditionally expressing these two proteins.

 

BOURDET-SICARD, R., RUDIGER, M., SANSONETTI, P.J.,  TRAN VAN NHIEU, G., 1999 Vinculin is unfolded by the Shigella  protein IpaA, and the complex promotes F-actin depolymerization. EMBO J., 18 :5853-5862

Identification of the eukaryotic partner and role of IpaA in remodeling of the actin cytoskeleton during Shigella entry.

 

EGILE, C., LOISEL, T.P., LAURENT, V., RONG LI, PANTALONI, D., SANSONETTI, P.J ., CARLIER, M.F., 1999 Activation of the CDC42 effector N-WASP by the Shigella IcsA  protein promotes actin nucleation by Arp2/3 complex and bacterial actin-ased motility. J. Cell Biol., 146 :1319-1332.

Demonstration of the role of Arp2/3 complex in IcsA-mediated actin nucleation via N-WASP.

 

COSTER, T., HOGE, C.W., VAN DE VERG, L.L., HARTMAN, A.B., OAKS, E.V., VENKATESAN, M.M., COHEN, D., ROBIN, G., FONTAINE-THOMSON, A., SANSONETTI, P.J ., HALE, T.L. 1999. Vaccination against shigellosis with attenuated Shigella flexneri  2a strain. Infect.Immun. 67:3437-3443 (citations: 97)

First evidence in a human phase IIb clinical trial that our rationally attenuated Shigella mutant is well tolerated and protective in humans.

 

MOUNIER, J., LAURENT, V., HALL, A., FORT, P., CARLIER, M-F., SANSONETTI, P.J.,  EGILE, C. 1999. Rho family GTPases control entry of Shigella flexneri into epithelial cells but not intracellular motility. J. Cell Science, 112:2069-2080

First identification of the role of small GTPases in Shigella entry, but not in entry of invasive pathogens in general.

 

SKOUDY, A., TRAN VAN NHIEU, G., MANTIS, N., ARPIN, M., MOUNIER, J., GOUNON, P., SANSONETTI, P.J. 1999 A functional role for Ezrin during Shigella  entry into epithelial cells. J. Cell Sci., 112:2059-2069.

 

TRAN VAN NHIEU, G., CARON, E., HALL, A., SANSONETTI, P.J . 1999. IpaC determines filopodia formation during Shigella  entry into epithelial cells. EMBO J., 18:3249-3262

The paper that definitely established that the C-terminal domain of IpaC, once exposed on the cytoplasmic side of the eukaryotic cell membrane, induced actin nucleation/reorganization.

 

BEATTY, W.L., MERESSE, S., GOUNON, P., DAVOUST, J., MOUNIER, J., SANSONETTI, P.J ., GORVEL, J-P. 1999 Trafficking of Shigella  lipopolysaccharide in polarized intestinal epithelial cells. J. Cell Biol., 145:689-698

Dissection of the cellular mechanisms of polarized transport of apically-delivered LPS by polarized epithelial cells.

 

SANSONETTI, P.J., ARONDEL, J., HUERRE, M., HARADA, A., MATSUSHIMA, K., 1999 Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis. Infect. Immun., 67:1471-1480

One of a series of papers deciphering in vivo, the function of major pro-inflammatory cytokines in the course of experimental shigellosis.

 

HILBI, H., MOSS, J.E., HERSH, D., CHEN. Y., ARONDEL, J., BANERJEE, S., FLAVELL, R.A., YUAN, J., SANSONETTI, P.J.,  ZYCHLINSKY, A. 1998 Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB. J. Biol. Chem., 273:32895-32900

The final demonstration that IpaB activates caspase-1 and causes macrophage apoptosis. Again, this all anticipated the concept of pyroptosis as subsequently “rediscovered”.

 

DUMENIL, G., OLIVO, J.C., PELLEGRINI, S., FELLOUS, M., SANSONETTI, P.J.,  TRAN VAN NHIEU, G. 1998 Interferon a inhibits a Src-mediated pathway necessary for Shigella -induced cytoskeletal rearrangements in epithelial cells. J. Cell Biol., 143:1-10

A possibly novel mechanism of control of Shigella invasion by Interferon.

 

DEMERS, B., SANSONETTI, P.J., PARSOT, C., 1998 Induction of type III secretion in Shigella flexneri  is associated with differential control of transcription of genes encoding secreted proteins. EMBO J., 17(10): 2894-2903

Another breakthrough paper characterizing the mxiE regulon of Shigella that couples activation of the TypeIII secretion system and the transcriptional induction of the genes of the “second wave” that encode a battery of regulators of the innate immune response.

 

TRAN VAN NHIEU, G., BEN ZE'EV, A., SANSONETTI, P.J., 1997 Modulation of bacterial entry in epithelial cells by association between vinculin and the Shigella  IpaA invasin. EMBO J., 16:2717-2729

First evidence that IpaA-vinculin interaction may contribute to remodeling of Shigella actin entry focus.

 

EGILE, C., d'HAUTEVILLE, H., PARSOT, C., SANSONETTI, P.J. 1997 SopA, an outer membrane protease achieving secretion and polar localization of IcsA in S. flexneri . Mol. Microbiol., 23:1063-1073

Demonstration that in Shigella, OmpT is replaced by the protease SopA that proceeds to cleavage of IcsA off the bacterial surface, while leaving enough IcsA at the bacterial pole, allowing directed/oriented actin-based motility.

 

SANSONETTI, P.J ., ARONDEL, J., CANTEY, R.J., PRÉVOST, M.C., HUERRE, M., 1996 Infection of rabbit Peyer's patches by Shigella flexneri : effect of adhesive or invasive bacterial phenotypes on follicularassociated epithelium. Infect. Immun., 64:2752-2764 (citations: 83)

A careful analysis of M-cells fate during Shigella infection and an evaluation of their role in the translocation of this pathogen through the epithelial lining.

 

ADAM, T., GIRY, M., BOQUET, P., SANSONETTI, P.J. 1996 Rho-dependent membrane folding causes Shigella  entry into epithelial cells. EMBO J., 15:3315-3321

A step in the dissection of the signaling cascade leading to actin nucleation, polymerization, assembly and remodeling during Shigella entry into epithelial cells.

 

ZYCHLINSKY, A. THIRUMALAI, K., ARONDEL, J., CANTEY, J.R., ALIPRANTIS, A.O., SANSONETTI, P.J.,  1996 In vivo  apoptosis in Shigella flexneri  infections. Infect. Immun., 64:5357-5365

The demonstration that macrophage apoptosis was not just an in vitro observation in the course of Shigella infection.

 

MÉNARD, R., PRÉVOST, M.C., GOUNON, P., SANSONETTI, P.J . DEHIO, C., 1996 The secreted Ipa complex of Shigella flexneri  promotes entry into mammalian cells. PNAS, 93:1254-1258

A paper that definitely validated the concept that the IpaB/IpaC complex was necessary and sufficient to promote Shigella entry into epithelial cells.

 

PHALIPON, A., KAUFMANN, M., MICHETTI, P., CAVAILLON, J.M., HUERRE, M., SANSONETTI, P.J.,  KRAEHENBÜHL, J.P., 1995 Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri  lipopolysaccharide protects against murine experimental shigellosis. J. Exp. Med., 182 : 769-778

Experimental demonstration and characterization of the basis of the serotype specific protection observed in shigellosis. IgA directed against the Shigella O-antigens are protective via immune exclusion at mucosal surface.

 

DEHIO, C., PRÉVOST, M.C., SANSONETTI, P.J.,  1995 Invasion of epithelial cells by Shigella flexneri  induces tyrosine phosphorylation of cortactin by a pp60c-src mediated signalling pathway. EMBO J., 14:2471-2482

First evidence for tyrosine phosphorylation of a host cell protein in the course of Shigella entry into cells. Cortactin would eventually turn out to be an essential component of the actin polymerization signaling cascade.

 

SANSONETTI, P.J.,  ARONDEL, J., CAVAILLON, J.M., HUERRE, M., 1995 Role of IL-1 in the pathogenesis of experimental shigellosis. J. Clin. Invest., 96 : 884-892

The essential demonstration that IL-1beta is a key cytokine in the early development of Shigella inflammation and rupture of the epithelial barrier.

 

ADAM T., ARPIN, M., PREVOST, M.C., GOUNON, P., SANSONETTI, P.J., 1995 Cytoskeletal rearrangements and the functional role of T-plastin during entry of Shigella flexneri  into HeLa cells. J. Cell Biol., 129: 367-381

A step in the dissection of the signaling cascade leading to actin nucleation, polymerization, assembly and remodeling during Shigella entry into epithelial cells.

 

PARSOT, C., MÉNARD, R., GOUNON, P., SANSONETTI, P.J., 1995 Enhanced secretion through the Shigella flexneri  Mxi-Spa translocon leads to assembly of extracellular proteins into macromolecular structures. Mol. Microbiol., 16: 291-300

One of the articles analyzing the mechanisms of regulation of Shigella type III secretion.

 

MÉNARD, R., SANSONETTI, P.J.,  PARSOT, C., VASSELON, T., 1994 Extracellular association and cytoplasmic partitioning of the IpaB and IpaC invasins of Shigella flexneri, Cell, 79:515-525

A key paper in Shigella pathogenesis, and more broadly in conceptualizing the TypeIII secretory system and understanding its mode of action.

 

PERDOMO, J.J., GOUNON, P., SANSONETTI, P.J.,  1994. Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri . J. Clin. Invest., 93:633-643

A key paper in which, for the first time, PMN were added basally to a monolayer of polarized epithelial cells on a filter, in the presence of apical bacteria, thereby allowing to model the role of attracted PMNs in the rupture of the epithelial barrier and its invasion by Shigella. These data were strikingly confirmed in the following article.

 

PERDOMO, J.J., CAVAILLON, J.M., HUERRE, M., OHAYON, H., GOUNON, P., SANSONETTI, P.J ., 1994 Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J. Exp. Med., 180:1307-1319

In vitro demonstration that inflammatory infiltrate of the infected epithelium by PMNs, facilitates rupture of the epithelial barrier and subsequent further bacterial invasion of this epithelium.

 

SANSONETTI, P.J ., MOUNIER, J., PREVOST, M.C., MEGE, R.M., 1994 Cadherin expression is required for the spread of Shigella flexneri  between epithelial cells. Cell, 76:829-839

The first evidence for a role of E-cadherin in bacterial-cell interaction. In this case the cell to cell spreading of Shigella.

 

ZYCHLINSKY, A., KENNY, B., MENARD, R., PREVOST, M.C., HOLLAND, I.B., SANSONETTI, P.J., 1994 IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol. Microbiol., 11:619-627 (155)

Important advance in understanding the molecular basis of macrophage-induced apoptosis by Shigella. Identification of the Shigella effector molecule.

 

ZYCHLINSKY, A., FITTING, C., CAVAILLON, J.M., SANSONETTI, P.J.,  1994 Interleukin 1 is released by macrophages during apoptosis induced by Shigella flexneri . J. Clin. Invest., 94:1328-1332

Demonstration that release of IL-1beta was associated with triggering of macrophage apoptosis by Shigella. This information led to the demonstration that caspase-1 was the executor caspase of macrophage apoptosis in this case. This discovery precluded by ten years the conceptualization of inflammasome and pyroptosis. We called it “pro-inflammatory apoptosis” at that time.

 

MÉNARD, R., SANSONETTI, P.J.,  PARSOT, C., 1994 The secretion of the Shigella flexneri  Ipa invasins is induced by the epithelial cell and controlled by IpaB and IpaD. EMBO J., 13:5293-5302

Another key paper in Shigella pathogenesis, and more broadly in conceptualizing the Type III secretory system and understanding its mode of action. Cell-contact induction of secretion was a key stone in the process.

 

MENARD, R., SANSONETTI, P.J ., PARSOT, C. 1993

Non polar mutagenesis of the ipa  genes defines IpaB, IpaC and IpaD as effectors of Shigella flexneri  entry into epithelial cells. J. Bacteriol., 175:5899-5906

A tool that was subsequently largely used to proceed to directed mutagenesis without disrupting downstream transcription in operons.

 

ALLAOUI, A., SANSONETTI, P.J ., PARSOT, C. 1993 MxiD, an outer membrane protein necessary for the secretion of the Shigella flexneri  Ipa invasins. Mol. Microbiol., 7:59-68

One of the key protein in assembly of the Type III secretory system.

 

GOLDBERG, M., BARZU, O., PARSOT, C., SANSONETTI, P.J.  1993 Unipolar localization and ATPase activity of IcsA, a Shigella flexneri  protein involved in intracellular movement. J. Bacteriol., 175:2189-2196

Advanced characterization of the polar localization and function of IcsA, the actin-nucleating autotransporter of Shigella.

 

PREVOST, M.C., LESOURD, M., ARPIN, M., VERNEL, F., MOUNIER, J., HELLIO, R., SANSONETTI, P.J.  1992 Unipolar reorganization of F-actin layer at bacterial division and bundling of actin filaments by plastin correlate with movement of Shigella flexenri  within HeLa cells. Infect. Immun., 60:4088-4099

An example of applying fine imaging techniques to better characterize dynamic cytoskeletal rearrangements during invasion of eukaryotic cells by pathogens.

 

ALLAOUI, A., SANSONETTI, PJ., PARSOT, C. MxiJ, a lipoprotein involved in secretion of Shigella Ipa invasins, is homologous to YscJ, a secretion factor of the Yersinia Yop proteins. 1992 J. Bacteriol., 174:7661-7669

One of the papers dissecting the function of the various proteins constituting the Shigella Type III secretory system.

 

ZYCHLINSKY, A., PREVOST, M.C., SANSONETTI, P.J.  1992 Shigella flexneri  induces apoptosis in infected macrophages. Nature, 358:167-169

Another founding paper of Cellular Microbiology. Shigella-induced apoptosis of macrophages opened the field of cell death in the presence of bacterial pathogens and anticipated on the concept of pyroptosis.

 

HIGH, N., MOUNIER, J., PREVOST, M.C., and SANSONETTI, P.J.  1992 IpaB of Shigella flexneri  causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J., 11:1991-1999

This has been for us a turn in understanding the connection between Type III secretion and entry.

 

MOUNIER, J., VASSELON, T., HELLIO, R., LESOURD, M. and SANSONETTI, P. J. 1992 Shigella flexneri  enters human colonic Caco-2 epithelial cells through their basolateral pole. Infect. Immun., 60:237-248

A conceptually major paper in our view of Shigella invasion of the intestinal epithelium.

 

SANSONETTI, P.J ., ARONDEL, J., FONTAINE, A., d'HAUTEVILLE, H., BERNARDINI, M. L. 1991 OmpB (osmo-regulation) and ics A (cell to cell spread) mutants of Shigella flexneri . Evaluation as vaccine candidates. Probes to study the pathogenesis of shigellosis. Vaccine, 9:416-422

A paper that not only validated the strategy of rational attenuation of our Shigella live attenuated vaccine candidates in the most relevant animal model, the macaque monkey, but also showed that in the colon/rectum, initial entry of Shigella occurred via the follicle-associated epithelium.

 

BERNARDINI, M. L., MOUNIER, J., d'HAUTEVILLE, H., COQUIS-RONDON, M., SANSONETTI, P. J.  1989 Identification of ics A, a plasmid locus of Shigella flexneri  which governs bacterial intra- and intercellular spread through interaction with F-actin. Proc. Natl. Acad. Sci. USA, 86:3867-3871

Another founding paper of Cellular microbiology. The first demonstration of actin-mediated cytosolic motility and cell to cell spread of a pathogen. Identification of the bacterial effector IcsA.

 

MOUNIER, J., RYTER, A., COQUIS RONDON, M., SANSONETTI, P. J . 1990 Intracellular and cell-to-cell spread of Listeria monocytogenes  involves interaction with F-actin in the Enterocytelike cell line Caco-2. Infect. Immun., 58:1048-1058

Confirmation that actin-dependant intracellular motility was a general process which did not only apply to Shigella.

 

FONTAINE, A., ARONDEL, J., SANSONETTI, P. J.  1988 Role of Shiga-toxin in the pathogenesis of bacillary dysentery as studied with a Tox-mutant of Shigella dysenteriae  1. Infect. Immun., 56:3099-3109

Likely the only paper that analyzed the role of Shiga toxin in a relevant animal model developing shigellosis: the macaque monkey. This paper showed that Shiga toxin essentially accounted for vascular rupture in the mucosa, thus causing ischemic colitis.

 

MAURELLI, A. T., SANSONETTI, P. J.  1988 Identification of a chromosomal gene controlling temperature regulated expression of Shigella  virulence. Proc. Natl. Acad. Sci. USA, 85:2820-2824

Identifiication of the gene regulating temperature-dependant expression of pathogenesis in Shigella.

 

GAILLARD, J. L., BERCHE, P., MOUNIER, J., RICHARD, S., SANSONETTI, P. J.  1987 Penetration and intracellular growth of Listeria monocytogenes  in the human enterocyte-like cell line CaCo2 : an in vitro model of pathogenesis. Infect. Immun., 55:2822-2829

Contributed to generalize the use of epithelial cells to study bacterial invasion.

 

CLERC, P., SANSONETTI, P. J.  1987 Entry of Shigella flexneri  into HeLa cells : evidence for directed phagocytosis involving actin polymerization and myosin accumulation. Infect. Immun., 55:2681-2688 (citations: 258)

Another founding papers of Cellular Microbiology for the first time demonstrating the need for actin polymerization tfor an invasive pathogen to penetrate into non-phagocytic cells.

 

CLERC, P., RYTER, A., MOUNIER, J., SANSONETTI, P.J.  1987 Plasmid-mediated early killing of eucaryotic cells by Shigella flexneri  as studied by infection of J774 macrophages. Infect. Immun., 55:521-527

The article that set the basis for the discovery that Shigella caused apoptotic death of macrophages.

 

BERCHE, P., GAILLARD, J. L., SANSONETTI, P. J.  1987 Intracellular growth of Listeria monocytogenes  as a prerequisite for in vivo  induction of T cell-mediated immunity. J. Immunol., 138:2266-2271

First evidence for the need for Listeria hemolysin to induce efficient protective T-cell response.

 

SANSONETTI, P. J.,  RYTER, A., CLERC. P., MAURELLI, A. T., MOUNIER, J. 1986 Multiplication of Shigella flexneri  within HeLa cells : lysis of the phagocytic vacuole and plasmid-mediated contact hemolysis. Infect. Immun., 51:461-469

First demonstration that an intracellular pathogen could escape into the cytoplasm.

 

GAILLARD, J. L., BERCHE, P., SANSONETTI, P. J . 1986 Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect. Immun., 52:50-55

Another founding paper of Cellular Microbiology: first example of transposon mutagenesis in Listeria and first demonstration of the role of Hemolysin in pathogenesis.

 

MAURELLI, A. T., BAUDRY, B., d'HAUTEVILLE, H., HALE,T. L., SANSONETTI, P. J.  1985 Cloning of plasmid DNA sequences involved in invasion of HeLa cells by Shigella flexneri . Infect. Immun. 49:164-171

First cloning of operons encoding cell invasion. A “tour de force” at that time (3 operons to clone on a single vector, stability, phenotypic screening, etc…).

 

SANSONETTI, P.J.,  HALE, T.L., DAMMIN, G.J., KAPFER, C., COLINS,H., FORMAL, S.B. 1983 Alterations in the pathogenicity of Escherichia coli  K-12 after transfer of plasmid and chromosomal genes from Shigella flexneri . Infect. Immun., 39:1392-1402

The first paper in which, starting from E. coli K12, we could reconstruct a fully virulent Shigella through stepwise transmission of the virulence plasmid and conjugative transfer of chromosiomal sequences. This work provided the bases for further characterization of the genes necessary for virulence.

 

SANSONETTI, P. J.,  KOPECKO, D. J., FORMAL, S. B. 1982 Involvement of a large plasmid in the invasive ability of Shigella flexneri . Infect. Immun., 35:852-860

This article and the one below started the field of Shigella pathogenesis by identifying a large virulence plasmid responsible for cell invasion. One of the funding papers of Cellular Microbiology

 

SANSONETTI, P. J ., KOPECKO, D. J., FORMAL, S. B. 1981 Shigella sonnei  plasmids : evidence that a large plasmid is necessary for virulence. Infect. Immun., 34:75-83

A founding paper of Shigella pathogenesis.

 

 

Reviews:

 

MARTEYN,B., GAZI,A., SANSONETTI PJ. Shigella: a model of virulence regulation in vivo

Gut Microbes, 2012 Mars:1;3(2)

A necessary review pointing to the need for increased analysis of gene regulation in pathogens in vivo. Shigella as a model.

 

KUFER, TA, SANSONETTI, PJ.  2011 NLR functions beyond pathogen recognition Nat. Immunol. 2011 Feb; 12(2):121-8

Increasing evidence indicate that Nod-like molecules (NLR) serve a variety of purposes that doare not exclusively related to the innate sensing of pathogens. This review is a snapshot of the current situation and points to the increasingly recognized role of TLRs in diverse human pathologies.

 

SANSONETTI PJ. To be or not to be a pathogen: that is the mucosally relevant question. Mucosal Immunol. 2011 Jan;4(1):8-14

A reflection on how mammals discriminate between the symbiotic microorganisms for which they establish a state of tolerance and pathogenic microorganisms that they need to quickly recognize and eliminate.

 

RAY K, MARTEYN B, SANSONETTI PJ,  TANG CM. Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nat Rev Microbiol. 2009 May;7(5):333-40

A review of the mechanisms supporting the intracellular growth of invasive bacteria.

 

SANSONETTI PJ , MEDZHITOV R. Learning tolerance while fighting ignorance. Cell. 2009 Aug 7;138(3):416-20

A reflection on the rules governing homeostasis of the gut in the presence of its microbiota. A “societal” view of symbiosis.

 

KUFER TA, SANSONETTI PJ. Sensing of bacteria: NOD a lonely job. Curr Opin Microbiol. 2007 Feb;10(1):62-9

A perspective on the function od Nod proteins.

 

PHALIPON A, SANSONETTI PJ. Shigella's ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival? Immunol Cell Biol. 2007 Feb-Mar;85(2):119-29

An exhaustive and early review of the mechanisms of subversion of the immune system by Shigella.

 

SANSONETTI, PJ.,  DI SANTO, J., 2007 Debugging how Bacteria Manipulate the Immune Response.

Immunity 26(2):149-61 (citations: 59)

A reflection on how homeostasis in maintained at the level of epthelia in the presence of symbiotic microorganisms, and how this homeostatic balance is disrupted by the pathogens.

 

SANSONETTI, P.J.  2006 The innate signaling of dangers and the dangers of innate signaling. Nat. Immunol., 7 (12) :1237-42

One of the first attempts at trying to synthesize data on extracellular and intracellular sensing of microbes, and at reflecting on how such systems are integrated and regulated, and how loss of control may occur, thus the title that was quite appreciated.

 

SANSONETTI, PJ,  2004 War and peace at mucosal surfaces. Nature Rev. Immunol., 4(12) :953-964

A reflection and a perspective on the spectrum of interactions between bacteria and the intestinal epithelium. From symbiosis to pathogenicity.

 

COSSART, P., SANSONETTI P.J.,  2004 Bacterial invasion : the paradigms of enteroinvasive pathogens. Science, 304 (5668) : 242-248

One very influential review on the molecular and cellular pathogenesis of enteroinvasive bacteria.

 

GIRARDIN S.E., HUGOT J.-P., SANSONETTI P.J.,  2003 Lessons from Nod2 studies : towards a link between Crohn's disease and bacterial sensing. Trends in Immunol., 24 (12):652-658

Among the first reviews that attempted to put the alteration of Nod molecules in the perspective of inflammatory bowel diseases such as Crohn’s disease.

 

PHILPOTT, D.J., GIRARDIN S.E., SANSONETTI, P.J.,  2001 Innate immune responses of epithelial cells following infection with bacterial pathogens Curr Opin Immunol, 2001 13:410-416

An attempt to rationalize the mechanisms of reprogramming of epithelial cells to become pro-inflammatory cells in function of the type of pathogens they encounter.

 

SANSONETTI, P.J.,  PHALIPON, A., 1999 M cells as ports of entry for enteroinvasive pathogens: mechanisms of interaction, consequences for the disease process. Seminars in Immunology, 11:193-203

One of the early reviews on the role of M-cells in facilitating pathogens translocation through the intestinal epithelium.

 

SANSONETTI, P.J.,  1998 Vaccines against enteric infections. Slaying the Hydra all at once or head by head ? Nature Medicine, Supplement, 4(5):499-500 (citations: 15)

A perspective regarding the development of anti-diarrheal vaccines.

 

ZYCHLINSKY, A., SANSONETTI, P.J.,  1997 Apoptosis as a proinflammatory event: what can we learn from bacteria-induced cell death ? Trends in Microbiology, 5:201-204

A nicely cited review because it conceptualizes the link between apoptosis, inflammation, and infection.

 

ZYCHLINSKY, A, SANSONETTI, PJ., 1997 Perspective in host/pathogen interactions. Apoptosis in bacterial pathogenesis. J Clin. Invest., 100:493-496 (citations: 142)

A nicely cited review because it conceptualizes the link between apoptosis, inflammation, and infection.

 

SANSONETTI, P. J . 1991 Genetic and molecular basis of epithelial cell invasion by Shigella  species. Rev. Infect. Dis., 13:S285-S292

A key stone review after the first steps of cellular microbiology of Shigella.

 

MAURELLI, A. T., SANSONETTI, P. J.  1988 Genetic determinants of Shigella  pathogenicity. Annual Review of Microbiology, 42:127-150

The first exhaustive review of Shigella genetics of pathogenesis following the discovery of the virulence plasmid.

 

SANSONETTI, P.J., FORMAL, S.B., HALE, T.L. 1983 Invasive enteric pathogens. Rev. Infectious Diseases, 5:S702-S707

First review on the genetic bases of virulence of enteroinvasive pathogens.

Updated on 22/10/2014

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