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Dive into the research topics where Lina M. Nilsson is active.

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Featured researches published by Lina M. Nilsson.


Molecular Microbiology | 2004

Shear‐dependent ‘stick‐and‐roll’ adhesion of type 1 fimbriated Escherichia coli

Wendy E. Thomas; Lina M. Nilsson; Manu Forero; Evgeni V. Sokurenko; Viola Vogel

It is generally assumed that bacteria are washed off surfaces as fluid flow increases because they adhere through ‘slip‐bonds’ that weaken under mechanical force. However, we show here that the opposite is true for Escherichia coli attachment to monomannose‐coated surfaces via the type 1 fimbrial adhesive subunit, FimH. Raising the shear stress (within the physiologically relevant range) increased accumulation of type 1 fimbriated bacteria on monomannose surfaces by up to two orders of magnitude, and reducing the shear stress caused them to detach. In contrast, bacterial binding to anti‐FimH antibody‐coated surfaces showed essentially the opposite behaviour, detaching when the shear stress was increased. These results can be explained if FimH is force‐activated; that is, that FimH mediates ‘catch‐bonds’ with mannose that are strengthened by tensile mechanical force. As a result, on monomannose‐coated surfaces, bacteria displayed a complex ‘stick‐and‐roll’ adhesion in which they tended to roll over the surface at low shear but increasingly halted to stick firmly as the shear was increased. Mutations in FimH that were predicted earlier to increase or decrease force‐induced conformational changes in FimH were furthermore shown here to increase or decrease the probability that bacteria exhibited the stationary versus the rolling mode of adhesion. This ‘stick‐and‐roll’ adhesion could allow type 1 fimbriated bacteria to move along mannosylated surfaces under relatively low flow conditions and to accumulate preferentially in high shear regions.


Journal of Biological Chemistry | 2006

Catch bond-mediated adhesion without a shear threshold: trimannose versus monomannose interactions with the FimH adhesin of Escherichia coli

Lina M. Nilsson; Wendy E. Thomas; Elena Trintchina; Viola Vogel; Evgeni V. Sokurenko

The FimH protein is the adhesive subunit of Escherichia coli type 1 fimbriae. It mediates shear-dependent bacterial binding to monomannose (1M)-coated surfaces manifested by the existence of a shear threshold for binding, below which bacteria do not adhere. The 1M-specific shear-dependent binding of FimH is consistent with so-called catch bond interactions, whose lifetime is increased by tensile force. We show here that the oligosaccharide-specific interaction of FimH with another of its ligands, trimannose (3M), lacks a shear threshold for binding, since the number of bacteria binding under static conditions is higher than under any flow. However, similar to 1M, the binding strength of surface-interacting bacteria is enhanced by shear. Bacteria transition from rolling into firm stationary surface adhesion as the shear increases. The shear-enhanced bacterial binding on 3M is mediated by catch bond properties of the 1M-binding subsite within the extended oligosaccharide-binding pocket of FimH, since structural mutations in the putative force-responsive region and in the binding site affect 1M- and 3M-specific binding in an identical manner. A shear-dependent conversion of the adhesion mode is also exhibited by P-fimbriated E. coli adhering to digalactose surfaces.


Journal of Bacteriology | 2007

Weak Rolling Adhesion Enhances Bacterial Surface Colonization

Brett N. Anderson; Albert M. Ding; Lina M. Nilsson; Kaoru Kusuma; Veronika Tchesnokova; Viola Vogel; Evgeni V. Sokurenko; Wendy E. Thomas

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.


Applied and Environmental Microbiology | 2006

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

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

ABSTRACT Soluble inhibitors find widespread applications as therapeutic drugs to reduce the ability of eukaryotic cells, bacteria, or viruses to adhere to surfaces and host tissues. Mechanical forces resulting from fluid flow are often present under in vivo conditions, and it is commonly presumed that fluid flow will further add to the inhibitive effect seen under static conditions. In striking contrast, we discover that when surface adhesion is mediated by catch bonds, whose bond life increases with increased applied force, shear stress may dramatically increase the ability of bacteria to withstand detachment by soluble competitive inhibitors. This shear stress-induced protection against inhibitor-mediated detachment is shown here for the fimbrial FimH-mannose-mediated surface adhesion of Escherichia coli. Shear stress-enhanced reduction of bacterial detachment has major physiological and therapeutic implications and needs to be considered when developing and screening drugs.


Molecular Microbiology | 2007

The cysteine bond in the Escherichia coli FimH adhesin is critical for adhesion under flow conditions

Lina M. Nilsson; Olga Yakovenko; Veronika Tchesnokova; Wendy E. Thomas; Mark A. Schembri; Viola Vogel; Per Klemm; Evgeni V. Sokurenko

Cysteine bonds are found near the ligand‐binding sites of a wide range of microbial adhesive proteins, including the FimH adhesin of Escherichia coli. We show here that removal of the cysteine bond in the mannose‐binding domain of FimH did not affect FimH–mannose binding under static or low shear conditions (≤ 0.2 dyne cm−2). However, the adhesion level was substantially decreased under increased fluid flow. Under intermediate shear (2 dynes cm−2), the ON‐rate of bacterial attachment was significantly decreased for disulphide‐free mutants. Molecular dynamics simulations demonstrated that the lower ON‐rate of cysteine bond‐free FimH could be due to destabilization of the mannose‐free binding pocket of FimH. In contrast, mutant and wild‐type FimH had similar conformation when bound to mannose, explaining their similar binding strength to mannose under intermediate shear. The stabilizing effect of mannose on disulphide‐free FimH was also confirmed by protection of the FimH from thermal and chemical inactivation in the presence of mannose. However, this stabilizing effect could not protect the integrity of FimH structure under high shear (> 20 dynes cm−2), where lack of the disulphide significantly increased adhesion OFF‐rates. Thus, the cysteine bonds in bacterial adhesins could be adapted to enable bacteria to bind target surfaces under increased shear conditions.


Structure | 2008

Beyond Induced-Fit Receptor-Ligand Interactions: Structural Changes that Can Significantly Extend Bond Lifetimes

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

While the lifetime of conventional receptor-ligand interactions is shortened by tensile mechanical force, some recently discovered interactions, termed catch bonds, can be strengthened by force. Motivated by the search for the underpinning structural mechanisms, we here explore the structural dynamics of the binding site of the bacterial adhesive protein FimH by molecular dynamics and steered molecular dynamics. While the crystal structure of only one FimH conformation has been reported so far, we describe two distinctively different conformations of the mannose-bound FimH binding site. Force-induced dissociation was slowed when the mannose ring rotated such that additional force-bearing hydrogen bonds formed with the base of the FimH binding pocket. The lifetime of the complex was further enhanced significantly by rigidifying this base. We finally show how even sub-angstrom spatial alterations of the hydrogen bonding pattern within the base can lead to significantly decreased bond lifetimes.


Biophysical Journal | 2006

Catch-Bond Model Derived from Allostery Explains Force-Activated Bacterial Adhesion

Wendy E. Thomas; Manu Forero; Olga Yakovenko; Lina M. Nilsson; Paolo Vicini; Evgeni V. Sokurenko; Viola Vogel


Nano Letters | 2004

A catch-bond based nanoadhesive sensitive to shear stress

Manu Forero; Wendy E. Thomas; Clint Bland; Lina M. Nilsson; Evgeni V. Sokurenko; Viola Vogel


Advanced Functional Materials | 2008

An Engineered Mannoside Presenting Platform: Escherichia coli Adhesion under Static and Dynamic Conditions†

Katrin A. Barth; Géraldine Coullerez; Lina M. Nilsson; Riccardo Castelli; Peter H. Seeberger; Viola Vogel; Marcus Textor


Archive | 2008

An Engineered Mannoside Presenting Platform:Escherichia coliAdhesion under Static and Dynamic Conditions**

ByKatrin A. Barth; Lina M. Nilsson; Riccardo Castelli; Peter H. Seeberger; Viola Vogel

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Manu Forero

University of Washington

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Riccardo Castelli

École Polytechnique Fédérale de Lausanne

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Olga Yakovenko

University of Washington

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