The shaft of the type 1 fimbriae regulates an external force to match the FimH catch bond

Abstract

Type 1 fimbriae mediate adhesion of uropathogenic Escherichia coli to host cells. It has been hypothesized that due to their ability to uncoil under exposure to force, fimbriae can reduce fluid shear stress on the adhesin-receptor interaction by which the bacterium adheres to the surface. In this work, we develop a model that describes how the force on the adhesin-receptor interaction of a type 1 fimbria varies as a bacterium is affected by a time-dependent fluid flow mimicking in vivo conditions. The model combines in vivo hydrodynamic conditions with previously assessed biomechanical properties of the fimbriae. Numerical methods are used to solve for the motion and adhesion force under the presence of time-dependent fluid profiles. It is found that a bacterium tethered with a type 1 pilus will experience significantly reduced shear stress for moderate to high flow velocities and that the maximum stress the adhesin will experience is limited to ∼120 pN, which is sufficient to activate the conformational change of the FimH adhesin into its stronger state but also lower than the force required for breaking it under rapid loading. Our model thus supports the assumption that the type 1 fimbria shaft and the FimH adhesin-receptor interaction are optimized to each other, and that they give piliated bacteria significant advantages in rapidly changing fluidic environments.

Figure 1

Symbolic representation of the nomenclature used in the model. The red point represents both the origin of the coordinate system and the position at which the adhesin adheres to a surface receptor. All entities displayed in the figure ($\theta ,F_P,F_{P_x},F_D$, etc.) generally take positive values and are described in detail in the text.

Figure 2

The trajectory of a bacterium tethered to a surface with a stiff linker (black dashed arrow) and an extendable pilus that elongates by uncoiling when the shear force is higher than the uncoiling force (gray solid arrows).

Figure 3

(A) Trajectory of a bacterium tethered with either a stiff linker (solid black curve) or a type 1 pilus (dashed curves) exposed to different flows, $S_1$, $S_2$, and $S_3$. The bacterium modeled has an effective radius of 1.0 μm and the length of the tether is 2 μm. The position given represents the center position of the bacterium. The gray dashed horizontal line therefore represents the position at which the bacterium touches the surface. (B) The force experienced by the adhesin in the various cases.

Figure 4

Trajectory of a bacterium exposed to five different transient sweeps. The solid black curves correspond to a bacterium attached by a stiff linker, whereas the dashed curves represent the trajectories for the bacterium attached with a type 1 pilus. In all cases, at time 0 the bacterium was exposed to a flow profile with the nominal shear rate of $S_0$ (corresponding to a linear shear with a flow velocity of 8 mm/s 3 μm above the surface). The sudden sweeps increase the shear rate at given times after the start of the simulation, as indicated in the key. (A) The shear rate was increased by a sweep from $S_0$ to $S_2$. (B) The shear rate was increased by a sweep from $S_0$ to $S_3$.

Figure 5

Force experienced by the adhesin for three of the flow conditions considered in Fig. 4 (when the transient sweep increases the shear rate at 0, 0.5, and 1 ms after the start of the simulation). The denotations of the various curves are indicated in the key, and the shear sweeps for A and B are as in Fig. 4.

Figure 6

Survival probability for a FimH-mannose bond when the bacterium is tethered via a stiff linker (solid curves) or a type 1 pilus (dashed curves) and exposed to three different shear rates, $S_1$, $S_2$, and $S_3$. The figure shows that for the stiff linker, the survival probability rapidly decreases toward zero in <0.2 ms, whereas for the type 1 pilus it remains close to 1 for a considerable time. (Inset) Decrease in the survival probability of the bacteria attached by the two types of tether. After 1.2 ms at $S_3$, the pilus is fully uncoiled (red dashed curve), i.e., the survival probability will rapidly go toward zero (not explicitly shown). The plateau represents the period after the catch bond changes conformation state from the weak to the strong binding configuration.