Early sequence of events triggered by the interaction of<i>N</i><i>eisseria meningitidis</i>with endothelial cells

Charles-Orszag, Arthur; Lagache, Thibault; Machata, Silke; Imhaus, Anne-Flore; Dumont, Audrey; Millien, Corinne; Olivo‐Marin, Jean‐Christophe; Duménil, Gérard

doi:10.1111/cmi.12248

Cited by 24 publications

(27 citation statements)

References 43 publications

(59 reference statements)

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“…1a), and were enriched in F-actin (Extended Data Fig. 1a), paralleling earlier in vitro studies 11,16,17 . This data shows that the endothelial cell plasma membrane is remodeled during vascular colonization by meningococcus in vivo , supporting the idea of a key role of plasma membrane remodeling in meningococcal pathogenesis, and warranting to further study its underlying mechanisms.…”

Section: Main Textsupporting

confidence: 85%

“…While membrane protrusions are enriched in F-actin 16 , our previous work has shown that inhibition of actin polymerization 11, 16, 17 or depletion of host cell ATP 17 have no effect on the remodeling of the host cell plasma membrane. Bacterial type IV pili (T4P), which are long retractile fibers with a diameter of 6 nm, are required for plasma membrane remodeling in addition to their role in specific adhesion to human cells 12, 17 . Indeed, adhesion of non-piliated bacteria mediated by non-fibrillar adhesins, like Opa, does not lead to the formation of plasma membrane protrusions 19 .…”

Section: Main Textmentioning

confidence: 83%

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Adhesion to nanofibers drives cell membrane remodeling through 1D wetting

Charles-Orszag

Tsai

Bonazzi

et al. 2018

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28The shape of cellular membranes is highly regulated by a set of conserved mechanisms. These 29 mechanisms can be manipulated by bacterial pathogens to infect cells. Human endothelial cell 30 plasma membrane remodeling by the bacterium Neisseria meningitidis is thought to be 31 essential during the blood phase of meningococcal infection, but the underlying mechanisms 32 are unknown. Here we show that plasma membrane remodeling occurs independently of F-33 actin, along meningococcal type IV pili fibers, by a novel physical mechanism we term "one-34 dimensional" membrane wetting. We provide a theoretical model that gives the physical basis 35 of 1D wetting and show that this mechanism occurs in model membranes interacting with 36 model nanofibers, and in human cells interacting with model extracellular matrices. It is thus 37 a new general principle driving the interaction of cells with their environment at the nanoscale 38 that is diverted by meningococcus during infection. 39Main text 40 Control of the shape of biological membranes is fundamental for the maintenance of 41 multiple functions in the eukaryotic cell 1 . Acting as the interface of the cell with its 42 surrounding environment, the plasma membrane is a particularly important compartment that 43 is subject to a precise control of its shape and dynamics. Plasma membrane remodeling occurs 44 at very small scales, for example in the biogenesis of caveolae 2 or during the formation of 45 clathrin coated pits 3 . At larger scales, remodeling of the plasma membrane plays an important 46 role in a wide variety of biological processes, such as the uptake of large particles by 47 phagocytosis 4 or in the formation of actin-based membrane structures that support cell 48 migration and probing of the extracellular environment, such as filopodia or lamellipodia 5 . In 49 the context of pathological conditions, especially in bacterial, viral and fungal infections, 50 pathogens manipulate the shape of the plasma membrane to enter host cells. This is often 51 achieved by diverting the actin cytoskeleton 6-8 . Other pathogens remain extracellular and must 52 then resist mechanical strains such as those generated by flow 9 . The bacterium Neisseria 53 meningitidis (or meningococcus) is a human pathogen that, while remaining extracellular 10 , 54 massively remodels the host cell plasma membrane to form filopodia-like protrusions that 55 intercalate between aggregated bacteria upon adhesion to the host cell surface. It was shown 56 in vitro that plasma membrane remodeling allows N. meningitidis to proliferate on the outside 57 of the host cell while mechanically resisting high shear stress levels 11 , suggesting a central role 58 for plasma membrane remodeling in the blood phase of N. meningitidis pathogenesis where 59 bacteria are subject to high shear. Colonization of the blood vessels by N. meningitidis 60 eventually leads to a loss of vascular function that translates into hemorrhagic lesions in 61 organs throughout the body, including the skin where it presents...

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Section: Main Textsupporting

confidence: 85%

Section: Main Textmentioning

confidence: 83%

Adhesion to nanofibers drives cell membrane remodeling through 1D wetting

Charles-Orszag

Tsai

Bonazzi

et al. 2018

Preprint

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“…We found that the formation of these clusters requires sufficient concentration of a third partner, Actn4, indicating the necessity of an optimal stoichiometric ratio of receptors and of this cytoskeletal protein. These clusters provide molecular platforms for the elongation of membrane protrusions that were shown to rapidly surround bacteria after their initial adhesion14 and to maintain stable adhesion of growing colonies despite the forces exerted by the blood flow215. In this context, the functional role of these structures would be to provide a sufficient number of binding sites for polymeric bacterial ligands.…”

Section: Discussionmentioning

confidence: 99%

“…β-arrestins then favour the local recruitment and activation of both cytoskeleton-associated and signalling proteins, resulting in remodelling of the apical plasma membrane beneath bacterial colonies1213. Ezrin and moesin, which accumulate within 2–4 min after bacterial contact14, are key players in the reorganization of the cortical actin cytoskeleton at bacterial adhesion sites13. Ultimately, local signalling events result in the formation of membrane protrusions surrounding bacteria and allow them to resist haemodynamic forces15.…”

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confidence: 99%

Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4

et al. 2017

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Neisseria meningitidis (meningococcus) is an invasive bacterial pathogen that colonizes human vessels, causing thrombotic lesions and meningitis. Establishment of tight interactions with endothelial cells is crucial for meningococci to resist haemodynamic forces. Two endothelial receptors, CD147 and the β2-adrenergic receptor (β2AR), are sequentially engaged by meningococci to adhere and promote signalling events leading to vascular colonization, but their spatiotemporal coordination is unknown. Here we report that CD147 and β2AR form constitutive hetero-oligomeric complexes. The scaffolding protein α-actinin-4 directly binds to the cytosolic tail of CD147 and governs the assembly of CD147–β2AR complexes in highly ordered clusters at bacterial adhesion sites. This multimolecular assembly process increases the binding strength of meningococci to endothelial cells under shear stress, and creates molecular platforms for the elongation of membrane protrusions surrounding adherent bacteria. Thus, the specific organization of cellular receptors has major impacts on host–pathogen interaction.

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“…123 Only a small proportion of these bacteria are able to disseminate from the oropharyngeal cavity to the bloodstream and cross the blood-brain barrier to eventually invade the meninges. 126 N. meningitidis has been observed around the capillaries of the subarachnoidal space, in the brain parenchyma and the choroidal plexuses, and inside brain vessels. 123 Specifically, the adhesion of N. meningitidis to endothelial cells promotes the cleavage of occludin by the metalloproteinase MMP-8.…”

Section: N Meningitidismentioning

confidence: 99%