Intermittent Pili-Mediated Forces Fluidize Neisseria meningitidis Aggregates Promoting Vascular Colonization

Abstract

Neisseria meningitidis, a bacterium responsible for meningitis and septicemia, proliferates and eventually fills the lumen of blood capillaries with multicellular aggregates. The impact of this aggregation process and its specific properties are unknown. We first show that aggregative properties are necessary for efficient infection and study their underlying physical mechanisms. Micropipette aspiration and single-cell tracking unravel unique features of an atypical fluidized phase, with single-cell diffusion exceeding that of isolated cells. A quantitative description of the bacterial pair interactions combined with active matter physics-based modeling show that this behavior relies on type IV pili active dynamics that mediate alternating phases of bacteria fast mutual approach, contact, and release. These peculiar fluid properties proved necessary to adjust to the geometry of capillaries upon bacterial proliferation. Intermittent attractive forces thus generate a fluidized phase that allows for efficient colonization of the blood capillary network during infection.

Continuum theory of active phase separation in cellular aggregates

“…Pili-mediated intercellular interactions of the bacteria are well studied and may serve as an important example to construct a microscopic model for active cellular force generation. N. gonorrhoeae bacteria have multiple (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) pili isotropically distributed over the cell body (see fig. 1 (c)) [27][28][29].…”

“…Multi-scale computer simulations have played an important role in the study of the physics of the formation of N. gonorrhoeae colonies [16][17][18]. Continuum approaches such as theories of active gels [19][20][21][22][23][24][25][26] so far do not capture important features of dense cellular aggregates.…”

Meningococcal disease: A paradigm of type‐IV pilus dependent pathogenesis

“…It was further shown in N. meningitidis that Tfp‐mediated interactions are source of cohesion forces favouring aggregate formation and fluidization. By generating intermittent attractive forces, pilus dynamics provides a viscous liquid‐like behaviour to the microcolonies, enabling them to adjust to changing geometries (Bonazzi et al, ). This feature may allow meningococcus to efficiently colonise the human microvasculature and provoke capillary occlusions.…”

Molecular interactions betweenNeisseria meningitidisand its human host

“…Furthermore, the dynamic of bacterial aggregates is key during colonisation of the blood capillary network. Bonazzi et al recently revealed that the ATPase PilT drives adaptation of aggregates to tubular geometry found in capillaries, a property necessary for colonisation of blood vessels (Bonazzi et al, ).…”

“…meningitidis may invade the bloodstream where it becomes one of the most harmful extracellular bacterial pathogen. In some cases, meningococcemia will rapidly progress toward a septic shock leading in the worst cases to a purpura fulminans , an acute systemic inflammatory response associated with an intravascular coagulation and tissue necrosis (Bonazzi et al, ; Brandtzaeg & van Deuren, ; Capel et al, ; Lecuyer et al, ; Lecuyer, Borgel, Nassif, & Coureuil, ). Alternatively, N .…”