Key Points
-
The targeting of the endothelium by bacteria and their toxins can produce severe pathologies, including: sepsis; endocarditis and focal vascular infections; septicaemia and ensuing septic metastasis and visceral abscesses; focal complications of bloodborne infections such as arthritis, meningitis and fetoplacental infections; and chronic infections leading to the formation of atherogenic or neo-angiogenic lesions.
-
Deregulation of innate immune responses by bacteria entering the cardiovascular system, combined with host susceptibility, can trigger systemic inflammatory syndrome, which damages the endothelium and can lead to immunoparalysis. Recent progress shows that neutrophil activation by platelets damages the endothelium.
-
Endothelial cells actively contribute to haemostatic homeostasis. Deregulation of this homeostasis by bloodborne pathogens can favour thrombosis and purpura fulminans. Recent work shows that some pathogenic bacteria can directly initiate the coagulation cascade.
-
Bacteria such as meningococci bind to and manipulate receptors at the endothelial cell surface to foster bacterial adhesion, circumvent shear stress forces that are exerted by the blood flow, recruit the polarity complex and destabilize intercellular junctions to disseminate in tissues.
-
Pathogenic bacteria trigger major endothelial cell membrane reorganizations, as do leukocytes during transcellular diapedesis across the endothelium. These reorganizations include the formation of transcellular tunnels that are induced by epidermal-cell differentiation inhibitor (EDIN) of Staphylococcus aureus and the formation of large membrane projections or invasomes in the case of Bartonella henselae.
-
Several toxins of pathogenic bacteria can hijack host inflammatory responses as well as the endothelial barrier function, inducing direct cytotoxic effects on the actin cytoskeleton and the endothelial cell.
Abstract
The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of pathogenic bacteria. Endothelial cells are actively involved in host responses to infectious agents, producing inflammatory cytokines, controlling coagulation cascades and regulating leukocyte trafficking. In this Review, a range of bacteria and bacterial toxins are used to illustrate how pathogens establish intimate interactions with endothelial cells, triggering inflammatory responses and coagulation processes and modifying endothelial cell plasma membranes and junctions to adhere to their surfaces and then invade, cross and even disrupt the endothelial barrier.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Valbuena, G. & Walker, D. H. The endothelium as a target for infections. Annu. Rev. Pathol. 1, 171–198 (2006).
Wolinsky, H. A proposal linking clearance of circulating lipoproteins to tissue metabolic activity as a basis for understanding atherogenesis. Circ. Res. 47, 301–311 (1980).
Aird, W. C. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ. Res. 100, 158–173 (2007).
Aird, W. C. Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ. Res. 100, 174–190 (2007). References 3 and 4 are thorough reviews on endothelium structure, heterogeneity and function.
Bazzoni, G. & Dejana, E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol. Rev. 84, 869–901 (2004).
Aird, W. C. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101, 3765–3777 (2003).
Angus, D. C. et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit. Care Med. 29, 1303–1310 (2001).
Campbell, L. A. & Kuo, C. C. Chlamydia pneumoniae — an infectious risk factor for atherosclerosis? Nature Rev. Microbiol. 2, 23–32 (2004).
Aird, W. C. Endothelium as a therapeutic target in sepsis. Curr. Drug Targets 8, 501–507 (2007).
Wojciak-Stothard, B. & Ridley, A. J. Rho GTPases and the regulation of endothelial permeability. Vascul. Pharmacol. 39, 187–199 (2003).
Carman, C. V. & Springer, T. A. Trans-cellular migration: cell-cell contacts get intimate. Curr. Opin. Cell Biol. 20, 533–540 (2008).
Rittirsch, D., Flierl, M. A. & Ward, P. A. Harmful molecular mechanisms in sepsis. Nature Rev. Immunol. 8, 776–787 (2008).
Pegu, A. et al. Human lymphatic endothelial cells express multiple functional TLRs. J. Immunol. 180, 3399–3405 (2008).
Loos, T. et al. TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis. Lab. Invest. 86, 902–916 (2006).
Kawai, T. & Akira, S. Signaling to NF-κB by Toll-like receptors. Trends Mol. Med. 13, 460–469 (2007).
Brodsky, I. E. & Medzhitov, R. Targeting of immune signalling networks by bacterial pathogens. Nature Cell Biol. 11, 521–526 (2009).
Jaffe, A. B. & Hall, A. RHO GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol. 21, 247–269 (2005).
Boquet, P. & Lemichez, E. Bacterial virulence factors targeting Rho GTPases: parasitism or symbiosis? Trends Cell Biol. 13, 238–246 (2003).
Munro, P. et al. Activation and proteasomal degradation of Rho GTPases by cytotoxic necrotizing factor-1 elicit a controlled inflammatory response. J. Biol. Chem. 279, 35849–35857 (2004). DNA macroarray analysis of the inflammatory responses that are induced in endothelial cells through direct activation of Rho GTPases by CNF1 of pathogenic E. coli .
Bokoch, G. M. Regulation of innate immunity by Rho GTPases. Trends Cell Biol. 15, 163–171 (2005).
Xie, Y., Kim, K. J. & Kim, K. S. Current concepts on Escherichia coli K1 translocation of the blood-brain barrier. FEMS Immunol. Med. Microbiol. 42, 271–279 (2004).
Miller, S. I., Ernst, R. K. & Bader, M. W. LPS, TLR4 and infectious disease diversity. Nature Rev. Microbiol. 3, 36–46 (2005).
Fraser, J. D. & Proft, T. The bacterial superantigen and superantigen-like proteins. Immunol. Rev. 225, 226–243 (2008).
Lorenz, E., Mira, J. P., Frees, K. L. & Schwartz, D. A. Relevance of mutations in the TLR4 receptor in patients with Gram-negative septic shock. Arch. Intern. Med. 162, 1028–1032 (2002).
Wang, L. et al. Crystal structure of a complete ternary complex of TCR, superantigen and peptide-MHC. Nature Struct. Mol. Biol. 14, 169–171 (2007).
Hotchkiss, R. S. & Nicholson, D. W. Apoptosis and caspases regulate death and inflammation in sepsis. Nature Rev. Immunol. 6, 813–822 (2006).
Arbibe, L. & Sansonetti, P. J. Epigenetic regulation of host response to LPS: causing tolerance while avoiding Toll errancy. Cell Host Microbe 1, 244–246 (2007).
Brown, K. A. et al. Neutrophils in development of multiple organ failure in sepsis. Lancet 368, 157–169 (2006).
Clark, S. R. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nature Med. 13, 463–469 (2007).
Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535 (2004). The first report of NETs.
Beiter, K. et al. An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr. Biol. 16, 401–407 (2006).
Kozek-Langenecker, S. A., Spiss, C. K., Michalek-Sauberer, A., Felfernig, M. & Zimpfer, M. Effect of prostacyclin on platelets, polymorphonuclear cells, and heterotypic cell aggregation during hemofiltration. Crit. Care Med. 31, 864–868 (2003).
Kessenbrock, K. et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nature Med. 15, 623–625 (2009).
Esmon, C. T. The interactions between inflammation and coagulation. Br. J. Haematol. 131, 417–430 (2005).
Niessen, F. et al. Dendritic cell PAR1–S1P3 signalling couples coagulation and inflammation. Nature 452, 654–658 (2008).
Faust, S. N. et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N. Engl. J. Med. 345, 408–416 (2001).
Levi, M., de Jonge, E. & van der Poll, T. New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology. Ann. Med. 36, 41–49 (2004).
Mullarky, I. K. et al. Infection-stimulated fibrin deposition controls hemorrhage and limits hepatic bacterial growth during listeriosis. Infect. Immun. 73, 3888–3895 (2005).
Kastrup, C. J. et al. Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'. Nature Chem. Biol. 4, 742–750 (2008). This work shows that clustering of some pathogenic bacteria can produce enough factors to directly activate the coagulation of human blood.
Mairey, E. et al. Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier. J. Exp. Med. 203, 1939–1950 (2006). The first demonstration that the force exerted by the blood flow can determine bacterial attachment sites along human vasculature.
Kim, K. S. Mechanisms of microbial traversal of the blood-brain barrier. Nature Rev. Microbiol. 6, 625–634 (2008). A recent review that discusses the possible mechanisms by which a pathogen can invade the brain.
Disson, O. et al. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature 455, 1114–1118 (2008). This study finds that the combined action of species-specific bacterial adhesion molecules is required for the development of fetoplacental listeriosis.
van Deuren, M., Brandtzaeg, P. & van der Meer, J. W. Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin. Microbiol. Rev. 13, 144–166 (2000).
Virji, M. et al. The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells. Mol. Microbiol. 5, 1831–1841 (1991).
Nassif, X. et al. Roles of pilin and PilC in adhesion of Neisseria meningitidis to human epithelial and endothelial cells. Proc. Natl Acad. Sci. USA 91, 3769–3773 (1994).
Virji, M. Pathogenic neisseriae: surface modulation, pathogenesis and infection control. Nature Rev. Microbiol. 7, 274–286 (2009). A comprehensive review of pathogenic neisseria, examining the known mechanisms used by these pathogens for niche establishment and the challenges that such mechanisms pose for infection control.
Kirchner, M., Heuer, D. & Meyer, T. F. CD46-independent binding of neisserial type IV pili and the major pilus adhesin, PilC, to human epithelial cells. Infect. Immun. 73, 3072–3082 (2005).
Merz, A. J., So, M. & Sheetz, M. P. Pilus retraction powers bacterial twitching motility. Nature 407, 98–102 (2000).
Maier, B., Koomey, M. & Sheetz, M. P. A force-dependent switch reverses type IV pilus retraction. Proc. Natl Acad. Sci. USA 101, 10961–10966 (2004).
Hoffmann, I., Eugene, E., Nassif, X., Couraud, P. O. & Bourdoulous, S. Activation of ErbB2 receptor tyrosine kinase supports invasion of endothelial cells by Neisseria meningitidis. J. Cell Biol. 155, 133–143 (2001).
Eugene, E. et al. Microvilli-like structures are associated with the internalization of virulent capsulated Neisseria meningitidis into vascular endothelial cells. J. Cell Sci. 115, 1231–1241 (2002).
Lambotin, M. et al. Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a PI3-Kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide. J. Cell Sci. 118, 3805–3816 (2005).
Doulet, N. et al. Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures. J. Cell Biol. 173, 627–637 (2006). The first demonstration that bacterial pathogens can hamper the triggering of host inflammatory responses by affecting the interaction of leukocytes with endothelial cells.
Lambotin, M. et al. Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide. J. Cell Sci. 118, 3805–3816 (2005).
Nassif, X., Bourdoulous, S., Eugene, E. & Couraud, P. O. How do extracellular pathogens cross the blood-brain barrier? Trends Microbiol. 10, 227–232 (2002).
Mikaty, G. et al. Neisseria meningitidis-induced host cell surface reorganization confers mechanical resistance to bacterial microcolonies in the bloodstream. PLoS Pathog. (in the press).
Nikulin, J., Panzner, U., Frosch, M. & Schubert-Unkmeir, A. Intracellular survival and replication of Neisseria meningitidis in human brain microvascular endothelial cells. Int. J. Med. Microbiol. 296, 553–558 (2006).
Pujol, C., Eugene, E., de Saint Martin, L. & Nassif, X. Interaction of Neisseria meningitidis with a polarized monolayer of epithelial cells. Infect. Immun. 65, 4836–4842 (1997).
Weksler, B. B. et al. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 19, 1872–1874 (2005).
Coureuil, M. et al. Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science 325, 83–87 (2009). This study elegantly shows how a bacterial pathogen may affect endothelial junction integrity by subverting the polarity complex.
Hurd, T. W., Gao, L., Roh, M. H., Macara, I. G. & Margolis, B. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nature Cell Biol. 5, 137–142 (2003).
Matter, K., Aijaz, S., Tsapara, A. & Balda, M. S. Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Curr. Opin. Cell Biol. 17, 453–458 (2005).
Bestebroer, J. et al. Staphylococcal SSL5 inhibits leukocyte activation by chemokines and anaphylatoxins. Blood 113, 328–337 (2009).
Bestebroer, J. et al. Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin-mediated neutrophil rolling. Blood 109, 2936–2943 (2007).
Ley, K., Laudanna, C., Cybulsky, M. I. & Nourshargh, S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nature Rev. Immunol. 7, 678–689 (2007).
Yamasaki, O. et al. Distribution of the exfoliative toxin D gene in clinical Staphylococcus aureus isolates in France. Clin. Microbiol. Infect. 12, 585–588 (2006).
Czech, A. et al. Prevalence of Rho-inactivating epidermal cell differentiation inhibitor toxins in clinical Staphylococcus aureus isolates. J. Infect. Dis. 184, 785–788 (2001).
Boyer, L. et al. Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors. J. Cell Biol. 173, 809–819 (2006). The first report of the induction of transient transcellular tunnels (macroapertures) in endothelial cells as a consequence of a decrease in RHOA activity.
Schwarz-Linek, U. et al. Pathogenic bacteria attach to human fibronectin through a tandem β-zipper. Nature 423, 177–181 (2003).
Schroder, A. et al. Staphylococcus aureus fibronectin binding protein-A induces motile attachment sites and complex actin remodeling in living endothelial cells. Mol. Biol. Cell 17, 5198–5210 (2006).
Tuomanen, E. Entry of pathogens into the central nervous system. FEMS Microbiol. Rev. 18, 289–299 (1996).
Finlay, B. B. & Cossart, P. Exploitation of mammalian host cell functions by bacterial pathogens. Science 276, 718–725 (1997).
Walker, D. H. & Ismail, N. Emerging and re-emerging rickettsioses: endothelial cell infection and early disease events. Nature Rev. Microbiol. 6, 375–386 (2008).
Voth, D. E. et al. The Coxiella burnetii ankyrin repeat domain-containing protein family is heterogeneous with C-terminal truncations that influence Dot/Icm-mediated secretion. J. Bacteriol. 191, 4232–4242 (2009).
Scheidegger, F. et al. Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation. Cell. Microbiol. 11, 1088–1101 (2009). This paper outlines a new model that allows the study of the molecular events underlying B. henselae -triggered angiogenesis.
Relman, D. A., Loutit, J. S., Schmidt, T. M., Falkow, S. & Tompkins, L. S. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N. Engl. J. Med. 323, 1573–1580 (1990).
Dehio, C. Bartonella-host-cell interactions and vascular tumour formation. Nature Rev. Microbiol. 3, 621–631 (2005).
Drancourt, M. et al. New serotype of Bartonella henselae in endocarditis and cat-scratch disease. Lancet 347, 441–443 (1996).
Kaiser, P. O. et al. The head of Bartonella adhesin A is crucial for host cell interaction of Bartonella henselae. Cell. Microbiol. 10, 2223–2234 (2008).
Szczesny, P. et al. Structure of the head of the Bartonella adhesin BadA. PLoS Pathog. 4, e1000119 (2008).
Manders, S. M. Bacillary angiomatosis. Clin. Dermatol. 14, 295–299 (1996).
Kyme, P. A. et al. Unusual trafficking pattern of Bartonella henselae-containing vacuoles in macrophages and endothelial cells. Cell. Microbiol. 7, 1019–1034 (2005).
Dehio, C., Meyer, M., Berger, J., Schwarz, H. & Lanz, C. Interaction of Bartonella henselae with endothelial cells results in bacterial aggregation on the cell surface and the subsequent engulfment and internalisation of the bacterial aggregate by a unique structure, the invasome. J. Cell Sci. 110, 2141–2154 (1997). A description of Bartonella -induced cell membrane reorganization into invasome structures.
Rhomberg, T. A., Truttmann, M. C., Guye, P., Ellner, Y. & Dehio, C. A translocated protein of Bartonella henselae interferes with endocytic uptake of individual bacteria and triggers uptake of large bacterial aggregates via the invasome. Cell. Microbiol. 11, 927–945 (2009).
Kempf, V. A. et al. Evidence of a leading role for VEGF in Bartonella henselae-induced endothelial cell proliferations. Cell. Microbiol. 3, 623–632 (2001).
Kempf, V. A. et al. Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections. Circulation 111, 1054–1062 (2005).
Schmid, M. C. et al. A translocated bacterial protein protects vascular endothelial cells from apoptosis. PLoS Pathog. 2, e115 (2006).
Johnson, K. E., Thorpe, C. M. & Sears, C. L. The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli. Clin. Infect. Dis. 43, 1587–1595 (2006).
Karmali, M. A. et al. Association of genomic O island 122 of Escherichia coli EDL 933 with verocytotoxin-producing Escherichia coli seropathotypes that are linked to epidemic and/or serious disease. J. Clin. Microbiol. 41, 4930–4940 (2003).
O'Brien, A. D. & Holmes, R. K. Shiga and Shiga-like toxins. Microbiol. Rev. 51, 206–220 (1987).
Romer, W. et al. Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature 450, 670–675 (2007). This article details a new mode of entry of Shiga toxin by self-induced membrane tubulation.
Warnier, M. et al. Trafficking of Shiga toxin/Shiga-like toxin-1 in human glomerular microvascular endothelial cells and human mesangial cells. Kidney Int. 70, 2085–2091 (2006).
Paton, A. W., Srimanote, P., Talbot, U. M., Wang, H. & Paton, J. C. A new family of potent AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. J. Exp. Med. 200, 35–46 (2004).
Karch, H. et al. New aspects in the pathogenesis of enteropathic hemolytic uremic syndrome. Semin. Thromb. Hemost. 32, 105–112 (2006).
Wolfson, J. J. et al. Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress-signalling pathways. Cell. Microbiol. 10, 1775–1786 (2008).
Byres, E. et al. Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature 456, 648–652 (2008). The discovery of the host cell receptor for SubAB of STEC.
Aktories, K. & Barbieri, J. T. Bacterial cytotoxins: targeting eukaryotic switches. Nature Rev. Microbiol. 3, 397–410 (2005).
Geny, B. et al. Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability. Am. J. Pathol. 170, 1003–1017 (2007).
Kirby, J. E. Anthrax lethal toxin induces human endothelial cell apoptosis. Infect. Immun. 72, 430–439 (2004).
Warfel, J. M., Steele, A. D. & D'Agnillo, F. Anthrax lethal toxin induces endothelial barrier dysfunction. Am. J. Pathol. 166, 1871–1881 (2005). This article reports lethal toxin of B. anthracis cleaves MAP kinase kinases to directly trigger the actin cytoskeleton reorganization that is responsible for an increase in endothelium permeability in human microvascular endothelial cells.
Gozes, Y., Moayeri, M., Wiggins, J. F. & Leppla, S. H. Anthrax lethal toxin induces ketotifen-sensitive intradermal vascular leakage in certain inbred mice. Infect. Immun. 74, 1266–1272 (2006).
Alfano, R. W. et al. Potent inhibition of tumor angiogenesis by the matrix metalloproteinase-activated anthrax lethal toxin: implications for broad anti-tumor efficacy. Cell Cycle 7, 745–749 (2008).
Moayeri, M. & Leppla, S. H. The roles of anthrax toxin in pathogenesis. Curr. Opin. Microbiol. 7, 19–24 (2004).
Bradley, K. A., Mogridge, J., Mourez, M., Collier, R. J. & Young, J. A. Identification of the cellular receptor for anthrax toxin. Nature 414, 225–229 (2001).
Scobie, H. M., Rainey, G. J., Bradley, K. A. & Young, J. A. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc. Natl Acad. Sci. USA 100, 5170–5174 (2003).
Bonuccelli, G. et al. ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry: implications for the pathogenesis of anthrax infection. Am. J. Physiol. Cell Physiol. 288, C1402–C1410 (2005).
Rmali, K. A., Al-Rawi, M. A., Parr, C., Puntis, M. C. & Jiang, W. G. Upregulation of tumour endothelial marker-8 by interleukin-1β and its impact in IL-1β induced angiogenesis. Int. J. Mol. Med. 14, 75–80 (2004).
Abrami, L., Leppla, S. H. & van der Goot, F. G. Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis. J. Cell Biol. 172, 309–320 (2006).
Sun, J., Lang, A. E., Aktories, K. & Collier, R. J. Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation. Proc. Natl Acad. Sci. USA 105, 4346–4351 (2008).
Duesbery, N. S. et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280, 734–737 (1998).
Moayeri, M., Haines, D., Young, H. A. & Leppla, S. H. Bacillus anthracis lethal toxin induces TNF-α-independent hypoxia-mediated toxicity in mice. J. Clin. Invest. 112, 670–682 (2003).
Rolando, M. et al. Injection of Staphylococcus aureus EDIN by the Bacillus anthracis protective antigen machinery induces vascular permeability. Infect. Immun. 77, 3596–3601 (2009).
Bhavsar, A. P., Guttman, J. A. & Finlay, B. B. Manipulation of host-cell pathways by bacterial pathogens. Nature 449, 827–834 (2007).
Bone, R. C. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 101, 1644–1655 (1992).
Voth, D. E. & Heinzen, R. A. Coxiella type IV secretion and cellular microbiology. Curr. Opin. Microbiol. 12, 74–80 (2009).
Merz, A. J. & So, M. Interactions of pathogenic Neisseriae with epithelial cell membranes. Annu. Rev. Cell Dev. Biol. 16, 423–457 (2000).
Bretscher, A., Edwards, K. & Fehon, R. G. ERM proteins and merlin: integrators at the cell cortex. Nature Rev. Mol. Cell Biol. 3, 586–599 (2002).
Weed, S. A. & Parsons, J. T. Cortactin: coupling membrane dynamics to cortical actin assembly. Oncogene 20, 6418–6434 (2001).
Selbach, M. & Backert, S. Cortactin: an Achilles' heel of the actin cytoskeleton targeted by pathogens. Trends Microbiol. 13, 181–189 (2005).
Yarden, Y. & Sliwkowski, M. X. Untangling the ErbB signalling network. Nature Rev. Mol. Cell Biol. 2, 127–137 (2001).
Ge, Z., Schauer, D. B. & Fox, J. G. In vivo virulence properties of bacterial cytolethal-distending toxin. Cell. Microbiol. 10, 1599–1607 (2008).
Shenker, B. J. et al. A novel mode of action for a microbial-derived immunotoxin: the cytolethal distending toxin subunit B exhibits phosphatidylinositol 3,4,5-triphosphate phosphatase activity. J. Immunol. 178, 5099–5108 (2007).
Lemonnier, M., Landraud, L. & Lemichez, E. Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology. FEMS Microbiol. Rev. 31, 515–534 (2007).
Vogelsgesang, M., Pautsch, A. & Aktories, K. C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins. Naunyn Schmiedebergs Arch. Pharmacol. 374, 347–360 (2007).
Popoff, M. R. et al. Ras, Rap, and Rac small GTP-binding proteins are targets for Clostridium sordellii lethal toxin glucosylation. J. Biol. Chem. 271, 10217–10224 (1996).
Acknowledgements
We apologize to all those authors in the field whose papers we could not cite because of space limitations. We thank L. Landraud and C. Dehio for discussions and N. Gauthier for the supplementary movie. We are supported by institutional funding from INSERM. Research in the E.L. laboratory is also supported by a grant from the Agence Nationale de la Recherche (ANR; grant RPV07055ASA) and the Association pour la Recherche sur le Cancer (ARC; grant 3800). Research in the S.B. and X.N. laboratories is also funded by grants from ANR and ARC. is M.L. is also funded by Institut Pasteur, ANR and FRM.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
41579_2010_BFnrmicro2269_MOESM1_ESM.mov
Supplementary information S1 | The movie shows the dynamics of opening and closure of macroapertures in human umbilical vein endothelial cells intoxicated by EDIN filmed by differential interference contrast. (MOV 4927 kb)
Glossary
- Atherogenesis
-
The process of atheromatous plaque formation during atherosclerosis.
- Inflammatory storm
-
An unspecific and massive release of inflammatory mediators.
- Toxic shock syndrome
-
Septic shock manifestations that are induced by bacterial toxins.
- Extrinsic pathway
-
The primary pathway for the initiation of blood coagulation, triggered by a thrombin burst; this is also called the tissue factor pathway.
- Intrinsic pathway
-
A secondary pathway for the initiation of blood coagulation that is classically triggered by contact activation of factor XII when blood comes into contact with negatively charged surfaces (potentially collagens); this is also called the contact activation pathway.
- Extravasation
-
The exit of leukocytes from the blood stream.
- Transendothelial diapedesis
-
The proess by which leukocytes cross the endothelium through large tunnels that are formed in endothelial cells.
- Leukocyte rolling
-
The method by which loosely attached leukocytes at the surface of the endothelium move.
Rights and permissions
About this article
Cite this article
Lemichez, E., Lecuit, M., Nassif, X. et al. Breaking the wall: targeting of the endothelium by pathogenic bacteria. Nat Rev Microbiol 8, 93–104 (2010). https://doi.org/10.1038/nrmicro2269
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrmicro2269
This article is cited by
-
Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for ‘leaky-gut’ in inflammatory bowel disease
Scientific Reports (2020)
-
Virulence factors and clonal diversity of Staphylococcus aureus in colonization and wound infection with emphasis on diabetic foot infection
European Journal of Clinical Microbiology & Infectious Diseases (2020)
-
Vascular surveillance by haptotactic blood platelets in inflammation and infection
Nature Communications (2020)
-
Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili
Nature Communications (2019)
-
Expression profiles of microRNAs in oxidized low-density lipoprotein-stimulated RAW 264.7 cells
In Vitro Cellular & Developmental Biology - Animal (2018)