Salmonella bacteria grip their host more tenaciously when pulled apart because complex adhesive proteins change their structure as stronger force is applied.

Pathogens must adhere to host tissue in order to survive and reproduce. They produce many adhesive proteins on their surface most of which exhibit slip-bond type binding with host compounds; in other words, the bonds slip and let go when pulled apart. Salmonella bacteria have evolved special binding proteins that exhibit catch-bond type adhesion to host cells—these bonds actually become stronger when pulled apart, up to a certain threshold. FimH is one of Salmonella's multi-domain adhesive proteins. The binding domain is a lectin pocket that binds to mannose on the surface of the host cell. This domain is linked to another part of the adhesive protein (a long pilin domain) which anchors FimH to the bacteria. When the bonds between the bacteria and its host are pulled apart by weak forces, the pilin domain holds tightly to the binding domain which in turn binds mannose with low force. But when the bonds between the bacteria and its host are pulled apart by stonger forces, the pilin domain is stretched away from the binding domain causing the structure of the binding pocket to shift so that it binds mannose with 100 times more force. In short, strong mechanical forces pull a binding inhibitor away from the binding domain increasing adhesion: a catch-bond. There is an optimum range within which catch-bonding occurs; when that range is exceeded, catch-bonds revert to slip-bonds.


"Receptor-ligand bonds strengthened by tensile mechanical force are referred to as catch bonds…mechanical force prolongs the lifetime of these bonds rather than shortens the lifetime by pulling the ligand out of the binding pocket." (Thomas et al. 2008:399)

"Catch bonds provide a way for cells to stabilize their attachments exactly when they need it most—when forces would otherwise pull the bonds apart...Above 11 pN, the trend reversed and these bonds, like any other adhesive interaction, could be overpowered by sufficient force. Thus, catch bonds have a biphasic response to force, with the longest lifetime at an intermediate level of force termed the critical force." (Thomas et al. 2008:400-1)

"[B]acterial adhesive protein, FimH, which binds to mannose residues on glycoproteins...undergoes a force-induced conformational change. Point mutations correlated this conformational change with stronger binding to target cells under shear stress." (Thomas et al. 2008:401-2)

"The presence of two distinct rate constants demonstrates the existence of two bound states...FimH forms catch bonds with mannose because of a force-induced switch between two distinct states...FimH has a deep pocket into which mannose docks, similar to many strong-binding receptor-ligand interactions such as biotin-avidin...FimH mediates a rolling adhesion even at lower shear stress and a stationary adhesion once activated by force." (Thomas et al. 2008:402)

"Most proteins respond to external stimuli by changing structure and thus function. A common means of regulation is allostery, in which a soluble compound binds to an allosteric site on a protein that regulates the structure and function of the active site because the two sites are spatially separated but structurally coupled...mechanical force, like a soluble compound, could act on an allosteric site of a catch bond rather than directly on the ligand-binding pocket. For example, the ligand-binding domain interacts with a second domain that acts as an allosteric inhibitor...Then mechanical force could pull the inhibitor from the regulatory site of the ligand-binding domain, favoring a high- activity over a low-activity state." (Thomas et al. 2008:403)

"[F]orce would activate FimH indirectly through a regulatory region rather than by acting directly on the active site. FimH has a lectin domain that binds mannose in a pocket at the tip and a pilin domain that integrates FimH into long fimbriae. In the simulations, force extended the linker chain that normally connects the two domains...extension of the linker chain activated FimH. The pilin domain, which anchors FimH to the bacteria, reduces the affinity of the ligand-binding lectin domain over 100-fold...biochemical interventions hypothesized to wedge the two domains apart increased the affinity of FimH for mannose...mechanical force extends the interdomain linker chain, which separates the inhibitory pilin domain from the lectin domain, leading to its allosteric activation...FimH-mannose bonds demonstrate catch bond behavior, but only when FimH contains the native allosteric regulation...the bonds act like slip bonds when FimH is allosterically preactivated. Thus, the structural simulations combined with mutagenesis and functional assays demonstrate that FimH is a catch bond because the interdomain region has an allosteric regulatory site that activates the binding site when it is in the extended conformation." (Thomas et al. 2008:409)

Journal article
Biophysics of Catch BondsAnnu. Rev. Biophys.February 14, 2008
Wendy E. Thomas, Viola Vogel, Evgeni Sokurenko

Living System/s