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The Many Faces of Bacterium-Endothelium Interactions during Systemic Infections

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  • Authors: Dorian Obino1, Guillaume Duménil2
  • Editors: Pascale Cossart3, Craig R. Roy4, Philippe Sansonetti5
    Affiliations: 1: Pathogenesis of Vascular Infections, Institut Pasteur, INSERM, Paris, France; 2: Pathogenesis of Vascular Infections, Institut Pasteur, INSERM, Paris, France; 3: Institut Pasteur, Paris, France; 4: Yale University School of Medicine, New Haven, Connecticut; 5: Institut Pasteur, Paris, France
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0010-2019
  • Received 04 June 2018 Accepted 10 January 2019 Published 08 March 2019
  • Guillaume Duménil, [email protected]
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  • Abstract:

    A wide variety of pathogens reach the circulatory system during viral, parasitic, fungal, and bacterial infections, causing clinically diverse pathologies. Such systemic infections are usually severe and frequently life-threatening despite intensive care, in particular during the age of antibiotic resistance. Because of its position at the interface between the blood and the rest of the organism, the endothelium plays a central role during these infections. Using several examples of systemic infections, we explore the diversity of interactions between pathogens and the endothelium. These examples reveal that bacterial pathogens target specific vascular beds and affect most aspects of endothelial cell biology, ranging from cellular junction stability to endothelial cell proliferation and inflammation.

  • Citation: Obino D, Duménil G. 2019. The Many Faces of Bacterium-Endothelium Interactions during Systemic Infections. Microbiol Spectrum 7(2):BAI-0010-2019. doi:10.1128/microbiolspec.BAI-0010-2019.


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A wide variety of pathogens reach the circulatory system during viral, parasitic, fungal, and bacterial infections, causing clinically diverse pathologies. Such systemic infections are usually severe and frequently life-threatening despite intensive care, in particular during the age of antibiotic resistance. Because of its position at the interface between the blood and the rest of the organism, the endothelium plays a central role during these infections. Using several examples of systemic infections, we explore the diversity of interactions between pathogens and the endothelium. These examples reveal that bacterial pathogens target specific vascular beds and affect most aspects of endothelial cell biology, ranging from cellular junction stability to endothelial cell proliferation and inflammation.

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Image of FIGURE 1

Schematic representation of the two main types of intercellular junctions within the endothelium. Adherens junctions (AJ) are made by the homophilic interaction of VE-cadherin and PECAM (also known as CD31). In contrast, claudins, occludin, and proteins from the junctional adhesion molecule (JAM) family are involved in establishing tight junctions. Connection with the actin cytoskeleton is ensured by proteins of the catenin family (alpha-, beta-, and p120-catenin) in the case of adherens junctions and by proteins from the zonula occludens family (ZO-1, -2, and -3) in the case of tight junctions.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0010-2019
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Image of FIGURE 2

Infection of the endothelium by . Following bacterial inoculation into the lumen of blood vessels, adheres at the surface of the endothelium through the surface expression of OmpA and OmpB. Binding of OmpA and -B to cell surface integrins induces the phagocytosis of bacteria and the remodeling of the cellular actin cytoskeleton. Then, hemolysin C- and/or phospholipase D-expressing bacteria escape phagosomal vesicles, proliferate intracellularly, and utilize cellular components, such as actin monomers and nutrients, to assemble actin comet tails, which support bacterial movement and cell-to-cell spreading. Both actin cytoskeleton remodeling and bacterial propagation participate in damaging infected vessels, including the destabilization of cellular junctions responsible for the increase in vessel permeability.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0010-2019
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Vascular colonization by . Once in the bloodstream, adheres to the endothelium thanks to the surface expression of Tfp. While proliferating, and owing to their autoaggregative property, bacteria form a tight microcolony at the surface of the endothelium, which ultimately leads to the congestion of the colonized vessel. Bacterial adhesion at the surface of endothelial cells induces a drastic remodeling of the host cell plasma membrane that forms membrane protrusions that interdigitate within the bacterial aggregate. In addition, pilus interaction with endothelial cell surface receptors, such as CD147 or β2-adrenergic receptor (β2AR), induces the reorganization of the actin cytoskeleton and intercellular junctions by recruiting their components underneath the microcolony. Together, these events are proposed to destabilize intercellular junctions, resulting in an increase in vessel permeability. , ; RBC, red blood cell; Cad, cadherin.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0010-2019
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The stepwise process leading to endocarditis. The appearance of sterile lesions (most often of unknown origin) on the heart valvular endothelium leads to the exposure of the underlying extracellular matrix (ECM). This in turn triggers the formation of a thrombus—characterized by the local deposition of platelets and fibrin at the surface of the damaged endothelium—that favors bacterial adhesion. While bacteria proliferate and spread, the valvular endothelium becomes more and more damaged, eventually leading to the failure of the valve and the need for its surgical replacement.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0010-2019
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-induced angioproliferation. Interactions of with the endothelium can occur at the single-bacterium level through bacterial expression of the adhesin A (BadA) protein. This triggers the phagocytosis of the cell surface-bound bacteria and results in their perinuclear accumulation within phagosomes. Similarly to , also forms aggregates that are internalized through a slower process within large vacuoles, referred to as invasomes. In both cases, the VirB-VirD4 type IV secretion system-dependent cytoplasmic release of effector proteins (Beps) by intravesicular bacteria promotes the proliferation and activation of the infected endothelial cells. This results in the secretion by the endothelium of proinflammatory (e.g., IL-8) and proangiogenic (e.g., VEGF) factors. As a consequence, cells from the innate immunity system, including neutrophils and macrophages, are locally recruited to fight the infection. Activated macrophages locally secrete VEGF, thus reinforcing the proangiogenic microenvironment. Combined with the bacterium-mediated endothelial cell proliferation, this particular environment promotes angiogenesis that ultimately leads to the local accumulation of new blood capillaries and the formation of bacillary angiomatosis lesions. RBC, red blood cell.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0010-2019
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