Elevated Shear Stress Protects
            <i>Escherichia coli</i>
            Cells Adhering to Surfaces via Catch Bonds from Detachment by Soluble Inhibitors

Nilsson, Lina; Thomas, Wendy E.; Sokurenko, Evgeni V.; Vogel, Viola

doi:10.1128/aem.72.4.3005-3010.2006

Cited by 59 publications

(55 citation statements)

References 38 publications

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“…The antiadhesive treatment used in this work, ␣MM, is not metabolized by E. coli, nor is it toxic, and so it does not affect the rate of growth of E. coli in planktonic conditions and must act by altering adhesion. We have shown previously that soluble inhibitor is effective in detaching rolling bacteria (36). Consistent with this, we observed here that ␣MM, even at a concentration below the IC 50 , was able to reduce colonization by FimH-wt E. coli.…”

Section: Discussionsupporting

confidence: 79%

“…However, we also show here that the addition of a soluble inhibitor could enhance the rate of surface colonization for strong-binding bacteria. We found earlier that ␣MM was not very effective in detaching bacteria bound in a strong stationary mode of adhesion (36). Instead of causing the FimH-hi E. coli cells to detach, the inhibitor appears to have caused them to roll slowly.…”

Section: Discussionmentioning

confidence: 97%

“…The protein-coated glass coverslips formed the bottom of a parallel-plate flow chamber (2. Other than the differences in the surfaces, these assays were performed as previously described (36). The bound bacteria were recorded in time-lapse digital videos with the camera shutter held open just long enough to blur out free-floating bacteria.…”

Section: Methodsmentioning

confidence: 99%

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Weak Rolling Adhesion Enhances Bacterial Surface Colonization

et al. 2007

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Bacterial adhesion to and subsequent colonization of surfaces are the first steps toward forming biofilms, which are a major concern for implanted medical devices and in many diseases. It has generally been assumed that strong irreversible adhesion is a necessary step for biofilm formation. However, some bacteria, such as Escherichia coli when binding to mannosylated surfaces via the adhesive protein FimH, adhere weakly in a mode that allows them to roll across the surface. Since single-point mutations or even increased shear stress can switch this FimH-mediated adhesion to a strong stationary mode, the FimH system offers a unique opportunity to investigate the role of the strength of adhesion independently from the many other factors that may affect surface colonization. Here we compare levels of surface colonization by E. coli strains that differ in the strength of adhesion as a result of flow conditions or point mutations in FimH. We show that the weak rolling mode of surface adhesion can allow a more rapid spreading during growth on a surface in the presence of fluid flow. Indeed, an attempt to inhibit the adhesion of strongly adherent bacteria by blocking mannose receptors with a soluble inhibitor actually increased the rate of surface colonization by allowing the bacteria to roll. This work suggests that (i) a physiological advantage to the weak adhesion demonstrated by commensal variants of FimH bacteria may be to allow rapid surface colonization and (ii) antiadhesive therapies intended to prevent biofilm formation can have the unintended effect of enhancing the rate of surface colonization.Biofilms consist of surface-associated colonies of bacteria (11, 45) and are a major concern for implanted medical devices and in many diseases. They are the dominant mode of bacterial life in nature and exist on biological as well as abiotic surfaces (11,45). Eradication of biofilms is more problematic than that of bacteria in the planktonic mode of growth, since biofilms are resistant to innate host defenses (21, 32, 51), mechanical removal, and antibiotic treatments (6, 52). Therefore, a more promising strategy that has been proposed is to prevent biofilm formation through interference with the earliest steps of formation (11,38,45). Surface adhesion, defined as the binding of a planktonic bacterium to a surface, is the first step, and it is generally assumed that strong irreversible adhesion is necessary for biofilm formation (9,14). The next step is surface colonization, defined as the spread of adherent bacteria across a surface through division. It has been suggested that biofilms can be prevented by restricting these early stages of colonization by blocking specific receptor-ligand interactions with soluble inhibitors or antibodies that block adhesion rather than prevent bacterial growth (39).Escherichia coli binding via the protein FimH provides a model system for studying surface adhesion and colonization for two reasons. First, E. coli is the most common cause of both urinary tract infections (22, 23) and bi...

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 97%

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Weak Rolling Adhesion Enhances Bacterial Surface Colonization

et al. 2007

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“…Binding assays under shear conditions were carried out in a flow chamber as previously published (11). Briefly, bacteria in buffer are passed over the surface of 1M-bovine serum albumin-coated dishes in a parallelplate flow chamber (GlycoTech, Gaithersburg, MD).…”

Section: Methodsmentioning

confidence: 99%

Differential Stability and Trade-Off Effects of Pathoadaptive Mutations in the Escherichia coli FimH Adhesin

et al. 2007

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FimH is the tip adhesin of mannose-specific type 1 fimbriae of Escherichia coli, which are critical to the pathogenesis of urinary tract infections. Point FimH mutations increasing monomannose (1M)-specific uroepithelial adhesion are commonly found in uropathogenic strains of E. coli. Here, we demonstrate the emergence of a mixed population of clonally identical E. coli strains in the urine of a patient with acute cystitis, where half of the isolates carried a glycine-to-arginine substitution at position 66 of the mature FimH. The R66 mutation induced an unusually strong 1M-binding phenotype and a 20-fold advantage in mouse bladder colonization. However, E. coli strains carrying FimH-R66, but not the parental FimH-G66, had disappeared from the patient's rectal and urine samples collected from 29 to 44 days later, demonstrating within-host instability of the R66 mutation. No FimH variants with R66 were identified in a large (>600 strains) sequence database of fimH-positive E. coli strains. However, several strains carrying genes encoding FimH with either S66 or C66 mutations appeared to be relatively stable in the E. coli population. Relative to FimH-R66, the FimH-S66 and FimH-C66 variants mediated only moderate increases in 1M binding but preserved the ability to enhance binding under flow-induced shear conditions. In contrast, FimH-R66 completely lost shearenhanced binding properties, with bacterial adhesion being inhibited by shear forces and lacking a rolling mode of binding. These functional trade-offs may determine the natural populational instability of this mutation or other pathoadaptive FimH mutations that confer dramatic increases in 1M binding strength.Most Escherichia coli strains express type 1 fimbriae, hairlike adhesive organelles that mediate mannose-sensitive binding to host glycoproteins. The tip subunit, adhesin FimH, mediates shear-enhanced adhesion to monomannose (1M) receptors; the strength of binding is relatively weak under static conditions but is dramatically increased at high flow (21,22). Binding properties of FimH can be dramatically altered by single point mutations that occur throughout the protein and are responsible for up to 15-fold increases in the ability of E. coli strains to bind 1M under static conditions (4,14,15,17,18). Uropathogenic strains tend to bind 1M significantly better than strains of intestinal origin, and 1M binding is correlated with the ability to bind uroepithelial cells and with colonization of the urinary bladder in the mouse model of urinary tract infection (15). Thus, FimH mutations resulting in enhanced 1M binding are pathogenicity adaptive (pathoadaptive) in nature.Though FimH variants are 99% identical at the protein level, evolutionary analysis indicates that mutations occur in the adhesin more frequently than in even the structurally diverse major subunit of type 1 fimbriae, FimA (23). At the same time, mutations that enhance 1M binding do not persist in evolutionary terms due to the trade-off effects of pathoadaptive mutations (15). However, the na...

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“…For example, FimH-mediated binding of E. coli and other enterobacteria to the GP2 receptor of M cells is considered to be a prerequisite for the mucosal immune response against these bacteria (15). Also, FimH locked in the HAS conformation is much more sensitive to inhibition by solubilized mannosylated compounds than FimH able to switch between LAS and HAS (31). Therefore, the effect of "activating" antibodies on the course of bacterial colonization could potentially be advantageous for clearing the organism from bacterial infection.…”

Section: Discussionmentioning

confidence: 99%

Type 1 Fimbrial Adhesin FimH Elicits an Immune Response That Enhances Cell Adhesion of Escherichia coli

et al. 2011

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Escherichia coli causes about 90% of urinary tract infections (UTI), and more than 95% of all UTI-causing E. coli express type 1 fimbriae. The fimbrial tip-positioned adhesive protein FimH utilizes a shear forceenhanced, so-called catch-bond mechanism of interaction with its receptor, mannose, where the lectin domain of FimH shifts from a low-to a high-affinity conformation upon separation from the anchoring pilin domain. Here, we show that immunization with the lectin domain induces antibodies that exclusively or predominantly recognize only the high-affinity conformation. In the lectin domain, we identified four high-affinity-specific epitopes, all positioned away from the mannose-binding pocket, which are recognized by 20 separate clones of monoclonal antibody. None of the monoclonal or polyclonal antibodies against the lectin domain inhibited the adhesive function. On the contrary, the antibodies enhanced FimH-mediated binding to mannosylated ligands and increased by severalfold bacterial adhesion to urothelial cells. Furthermore, by natural conversion from the high-to the low-affinity state, FimH adhesin was able to shed the antibodies bound to it. When whole fimbriae were used, the antifimbrial immune serum that contained a significant amount of antibodies against the lectin domain of FimH was also able to enhance FimH-mediated binding. Thus, bacterial adhesins (or other surface antigens) with the ability to switch between alternative conformations have the potential to induce a conformation-specific immune response that has a function-enhancing rather than -inhibiting impact on the protein. These observations have implications for the development of adhesin-specific vaccines and may serve as a paradigm for antibody-mediated enhancement of pathogen binding.

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Elevated Shear Stress Protects Escherichia coli Cells Adhering to Surfaces via Catch Bonds from Detachment by Soluble Inhibitors

Cited by 59 publications

References 38 publications

Weak Rolling Adhesion Enhances Bacterial Surface Colonization

Weak Rolling Adhesion Enhances Bacterial Surface Colonization

Differential Stability and Trade-Off Effects of Pathoadaptive Mutations in the Escherichia coli FimH Adhesin

Type 1 Fimbrial Adhesin FimH Elicits an Immune Response That Enhances Cell Adhesion of Escherichia coli

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