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Björnham, Oscar
Publications (10 of 15) Show all publications
Bugaytsova, J. A., Björnham, O., Chernov, Y. A., Gideonsson, P., Henriksson, S., Mendez, M., . . . Boren, T. (2017). Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Cell Host and Microbe, 21(3), 376-389
Open this publication in new window or tab >>Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence
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2017 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389Article in journal (Refereed) Published
Abstract [en]

The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

Place, publisher, year, edition, pages
CELL PRESS, 2017
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-132788 (URN)10.1016/j.chom.2017.02.013 (DOI)000396375600023 ()28279347 (PubMedID)
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2019-05-24Bibliographically approved
Axner, O., Andersson, M., Björnham, O., Castelain, M., Klinth, J., Koutris, E. & Schedin, S. (2011). Assessing bacterial adhesion on an individual adhesin and single pili level using optical tweezers . In: D. Line and A. Goldman (Ed.), Bacterial adhesion: chemistry, biology and physics (pp. 301-313). Berlin: Springer Berlin/Heidelberg
Open this publication in new window or tab >>Assessing bacterial adhesion on an individual adhesin and single pili level using optical tweezers
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2011 (English)In: Bacterial adhesion: chemistry, biology and physics / [ed] D. Line and A. Goldman, Berlin: Springer Berlin/Heidelberg, 2011, p. 301-313Chapter in book (Refereed)
Abstract [en]

Optical tweezers (OT) are a technique that, by focused laser light, can both manipulate micrometer sized objects and measure minute forces (in the pN range) in biological systems. The technique is therefore suitable for assessment of bacterial adhesion on an individual adhesin-receptor and single attachment organelle (pili) level. This chapter summarizes the use of OT for assessment of adhesion mechanisms of both non-piliated and piliated bacteria. The latter include the important helix-like pili expressed by uropathogenic Escherichia coli (UPEC), which have shown to have unique and intricate biomechanical properties. It is conjectured that the large flexibility of this type of pili allows for a redistribution of an external shear force among several pili, thereby extending the adhesion lifetime of bacteria. Systems with helix-like adhesion organelles may therefore act as dynamic biomechanical machineries, enhancing the ability of bacteria to withstand high shear forces originating from rinsing flows such as in the urinary tract. This implies that pili constitute an important virulence factor and a possible target for future anti-microbial drugs.

Place, publisher, year, edition, pages
Berlin: Springer Berlin/Heidelberg, 2011
Series
Advances in experimental medicine and biology, ISSN 0065-2598 ; 715
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Atom and Molecular Physics and Optics
Research subject
Physical Biology; Physics
Identifiers
urn:nbn:se:umu:diva-51811 (URN)10.1007/978-94-007-0940-9_19 (DOI)000291365200019 ()21557072 (PubMedID)
Available from: 2012-02-02 Created: 2012-02-02 Last updated: 2018-06-08Bibliographically approved
Björnham, O. & Axner, O. (2010). Catch-Bond behavior of bacteria binding by slip bonds. Biophysical Journal, 99(5), 1331-1341
Open this publication in new window or tab >>Catch-Bond behavior of bacteria binding by slip bonds
2010 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 99, no 5, p. 1331-1341Article in journal (Refereed) Published
Abstract [en]

It is shown that multipili-adhering bacteria expressing helix-like pili binding by slip bonds can show catch-bond behavior. When exposed to an external force, such bacteria can mediate adhesion to their hosts by either of two limiting means: sequential or simultaneous pili force exposure (referring to when the pili mediate force in a sequential or simultaneous manner, respectively). As the force is increased, the pili can transition from sequential to simultaneous pili force exposure. Since the latter mode of adhesion gives rise to a significantly longer bacterial adhesion lifetime than the former, this results in a prolongation of the lifetime, which shows up as a catch-bond behavior. The properties and conditions of this effect were theoretically investigated and assessed in some detail for dual-pili-adhering bacteria, by both analytical means and simulations. The results indicate that the adhesion lifetime of such bacteria can be prolonged by more than an order of magnitude. This implies that the adhesion properties of multibinding systems cannot be directly conveyed to the individual adhesion-receptor bonds.

Keywords
Catch bond, slip bond, multipili, cooperative, binding, bacterium, adhesion, in vivo
National Category
Biophysics
Research subject
Physical Biology
Identifiers
urn:nbn:se:umu:diva-36157 (URN)10.1016/j.bpj.2010.06.003 (DOI)000281721500002 ()
Available from: 2010-09-21 Created: 2010-09-21 Last updated: 2018-06-08Bibliographically approved
Axner, O., Björnham, O., Castelain, M., Koutris, E., Schedin, S., Fällman, E. & Andersson, M. (2010). Unraveling the secrets of bacterial adhesion organelles using single molecule force spectroscopy (96ed.). In: Springer series in chemical physics: single molecule spectroscopy in chemistry, physics and biology (pp. 337-362). Springer Verlag
Open this publication in new window or tab >>Unraveling the secrets of bacterial adhesion organelles using single molecule force spectroscopy
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2010 (English)In: Springer series in chemical physics: single molecule spectroscopy in chemistry, physics and biology, Springer Verlag , 2010, 96, p. 337-362Chapter in book (Other academic)
Abstract [en]

Many types of bacterium express micrometer-long attachment organelles (so called pili) whose role is to mediate adhesion to host tissue. Until recently, little was known about their function in the adhesion process. Forcemeasuring  ptical tweezers (FMOT) have since then been used to unravel the  iomechanical properties of various types of pili, primarily those from uropathogenic E. coli, in particular their force-vs.-elongation response, but lately also some properties of the adhesin situated and the distal end of the pilus. This knowledge provides an understanding of how piliated bacteria can sustain external shear forces caused by rinsing processes, e.g. urine flow. It has been found that anytypes of pilus exhibit unique and complex force-vs.-elongation responses. It has been conjectured that their dissimilar properties impose significant differences in their ability to sustain external forces and that different types of pilus therefore have dissimilar predisposition to withstand different types of rinsing conditions. An understanding of these properties is of high importance since it can serve as a basis for finding new means to combat bacterial adhesion, including that caused by antibiotic-resistance bacteria. This work presents a review of the current status of the assessment of biophysical properties of individual pili on single bacteria exposed to strain/stress, primarily by the FMOT technique. It also addresses, for the first time, how the elongation and retraction properties of the rod couple to the adhesive properties of the tip adhesin.

Place, publisher, year, edition, pages
Springer Verlag, 2010 Edition: 96
Series
Nobel Symposium 138: Single Molecule Spectroscopy in Chemistry, Physics and Biosciences, ISSN 0172-6218 ; 138
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:umu:diva-21488 (URN)978-3-642-02596-9 (ISBN)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
Axner, O., Björnham, O., Castelain, M., Koutris, E., Schedin, S., Fällman, E. & Andersson, M. (2010). Unraveling the secrets of bacterial adhesion organelles using single-molecule force spectroscopy. In: Gräslund, Astrid, Rigler, Rudolf & Widengren, Jerker (Ed.), Single molecule spectroscopy in chemistry, physics and biology: Nobel symposium. Paper presented at Nobel Symposium 138: Single Molecule Spectroscopy in Chemistry, Physics and Biosciences, Jun 01-06, 2008, Sanga-Saby, SWEDEN (pp. 337-362). Springer
Open this publication in new window or tab >>Unraveling the secrets of bacterial adhesion organelles using single-molecule force spectroscopy
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2010 (English)In: Single molecule spectroscopy in chemistry, physics and biology: Nobel symposium / [ed] Gräslund, Astrid, Rigler, Rudolf & Widengren, Jerker, Springer, 2010, p. 337-362Conference paper, Published paper (Refereed)
Abstract [en]

Many types of bacterium express micrometer-long attachment organelles (so-called pili) whose role is to mediate adhesion to host tissue. Until recently, little was known about their function in the adhesion process. Force-measuring optical tweezers (FMOT) have since then been used to unravel the biomechanical properties of various types of pili, primarily those from uropathogenic E. coli, in particular their force-vs.-elongation response, but lately also some properties of the adhesin situated at the distal end of the pilus. This knowledge provides an understanding of how piliated bacteria can sustain external shear forces caused by rinsing processes, e.g., urine flow. It has been found that many types of pilus exhibit unique and complex force-vs.-elongation responses. It has been conjectured that their dissimilar properties impose significant differences in their ability to sustain external forces and that different types of pilus therefore have dissimilar predisposition to withstand different types of rinsing conditions. An understanding of these properties is of high importance since it can serve as a basis for finding new means to combat bacterial adhesion, including that caused by antibiotic-resistance bacteria. This work presents a review of the current status of the assessment of biophysical properties of individual pili on single bacteria exposed to strain/stress, primarily by the FMOT technique. It also addresses, for the first time, how the elongation and retraction properties of the rod couple to the adhesive properties of the tip adhesin.

Place, publisher, year, edition, pages
Springer, 2010
Series
Springer Series in Chemical Physics, ISSN 0172-6218 ; 96
Keywords
Coli P-pili, Uropathogenic escherichia coli, Optical tweezers, Physical properties, Extraintestinal infections, Radiation pressure, Energy landscapes, Sticky chain, Type-1 Pili, Bonds
National Category
Chemical Sciences Atom and Molecular Physics and Optics Physical Sciences
Identifiers
urn:nbn:se:umu:diva-109061 (URN)10.1007/978-3-642-02597-6_18 (DOI)000285735900018 ()978-3-642-02596-9 (ISBN)
Conference
Nobel Symposium 138: Single Molecule Spectroscopy in Chemistry, Physics and Biosciences, Jun 01-06, 2008, Sanga-Saby, SWEDEN
Available from: 2015-09-18 Created: 2015-09-17 Last updated: 2018-06-07Bibliographically approved
Björnham, O. (2009). A study of bacterial adhesion on a single-cell level by means of force measuring optical tweezers and simulations. (Doctoral dissertation). Umeå: Print & Media
Open this publication in new window or tab >>A study of bacterial adhesion on a single-cell level by means of force measuring optical tweezers and simulations
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The intriguing world of microbiology is nowadays accessible for detailed exploration at a single–molecular level. Optical tweezers are a novel instrument that allows for non–invasive manipulation of single cells by the sole use of laser light and operates on the nano– and micrometer scale which corresponds to the same length scale as living cells. Moreover, forces within the field of microbiology are typically in the picoNewton range which is in accordance with the capability of force measuring optical tweezers systems. Both these conformabilities imply that force measuring optical tweezers is suitable for studies of single living cells. This thesis focuses on the mechanisms of bacterial attachments to host cells which constitute the first step in bacterial infection processes. Bacteria bind specifically to host receptors by means of adhesins that are expressed either directly on the bacterial membrane or on micrometer–long adhesion organelles that are called pili. The properties of single adhesin–receptor bonds that mediate adherence of the bacterium Helicobacter pylori are first examined at various acidities. Further on, biomechanical properties of P pili expressed by Escherichia coli are presented to which computer simulations, that capture the complex kinetics of the pili structure and precisely replicate measured data, are applied. Simulations are found to be a powerful tool for investigations of adhesive attributes of binding systems and are utilized in the analyses of the specific binding properties of P pili on a single–pilus level. However, bacterial binding systems generally involve a multitude of adhesin–receptor bonds. To explore bacterial attachments, the knowledge from single–pilus studies is brought into a full multipili attachment scenario which is analyzed by means of theoretical treatments and simulations. The results are remarkable in several aspects. Not only is it found that the intrinsic properties of P pili are composed in an optimal combination to promote strong multipili bindings. The properties of the pili structure itself are also found to be optimized with respect to its in vivo environment. Indeed, the true meaning of the attributes derived at a single–pilus level cannot be unraveled until a multipili–binding system is considered. Whereas detailed studies are presented for the helix–like P pili expressed by Gram–negative Escherichia coli, conceptual studies are presented for the open coil–like T4 pili expressed by Gram–positive Streptococcus pneumoniae. The structural and adhesive properties of these two types of pili differ considerably. These dissimilarities have far–reaching consequences on the adhesion possibilities at both single–pilus and multipili levels which are discussed qualitatively. Moreover, error analyses of conventional data processing methods in dynamic force spectroscopy as well as development of novel analysis methods are presented. These findings provide better understanding of how to perform refined force measurements on single adhesion organelles as well as how to improve the analyses of measurement data to obtain accurate parameter values of biomechanical entities. In conclusion, this thesis comprises a study of bacterial adhesion organelles and the way they cooperate to establish efficient attachment systems that can successfully withstand strong external forces that acts upon bacteria. Such systems can resist, for instance, rinsing effects and thereby allow bacteria to colonize their host. By understanding the complexity, and thereby possible weaknesses, of bacterial attachments, new targets for combating bacterial infections can be identified.

Place, publisher, year, edition, pages
Umeå: Print & Media, 2009. p. 108
National Category
Physical Sciences
Research subject
Physics; cell research; molecular cell biology
Identifiers
urn:nbn:se:umu:diva-21493 (URN)978-91-7264-765-7 (ISBN)
Public defence
2009-05-08, N420, Naturvetarhuset, Umeå Universitet, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2009-04-17 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
Castelain, M., Koutris, E., Andersson, M., Wiklund, K., Björnham, O., Schedin, S. & Axner, O. (2009). Characterization of the Biomechanical Properties of T4 Pili Expressed by Streptococcus pneumoniae – A Comparison between Helix-like and Open Coil-like Pili. ChemPhysChem, 10(9-10), 1533-1540
Open this publication in new window or tab >>Characterization of the Biomechanical Properties of T4 Pili Expressed by Streptococcus pneumoniae – A Comparison between Helix-like and Open Coil-like Pili
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2009 (English)In: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 10, no 9-10, p. 1533-1540Article in journal (Refereed) Published
Abstract [en]

Bacterial adhesion organelles, known as fimbria or pili, are expressed by Gram–positive as well as Gram–negative bacteria families. These appendages play a key role in the first steps of the invasion and infection processes, and they therefore provide bacteria with pathogenic abilities. To improve the knowledge of pili-mediated bacterial adhesion to host cells and how these pili behave under the presence of an external force, we first characterize, using force measuring optical tweezers, open coil-like T4 pili expressed by Gram–positive Streptococcus pneumoniae with respect to their biomechanicalproperties. It is shown that their elongation behavior can be well described by the worm-like chain model and that they possess a large degree of flexibility. Their properties are then compared with those of helix-like pili expressed by Gram–negative uropathogenic Escherichia coli (UPEC), which have different pili architecture. The differences suggest that these two types of pili have distinctly dissimilar mechanisms to adhere and sustain external forces. Helix-like pili expressed by UPEC bacteria adhere to host cells by single adhesins located at the distal end of the pili while their helix-like structures act as shock absorbers to dampen the irregularly shear forces induced by urine flow and to increase the cooperativity of the pili ensemble. Open coil-like pili expressed by S. pneumoniae adhere to cells by a multitude of adhesins distributed along the pili. It is hypothesized that these two types of pili represent different strategies of adhering to host cells in the presence of external forces. When exposed to significant forces, bacteria expressing helix-like pili remain attached bydistributing the external force among a multitude of pili, whereas bacteria expressing open coil-like pili sustain large forces primarily by their multitude of binding adhesins.

National Category
Other Physics Topics
Identifiers
urn:nbn:se:umu:diva-21489 (URN)10.1002/cphc.200900195 (DOI)000267928100027 ()19565578 (PubMedID)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
Björnham, O., Bugaytsova, J., Borén, T. & Schedin, S. (2009). Dynamic force spectroscopy of the Helicobacter pylori BabA-Lewis b binding. Biophysical Chemistry, 143(1-2), 102-105
Open this publication in new window or tab >>Dynamic force spectroscopy of the Helicobacter pylori BabA-Lewis b binding
2009 (English)In: Biophysical Chemistry, ISSN 0301-4622, E-ISSN 1873-4200, Vol. 143, no 1-2, p. 102-105Article in journal (Refereed) Published
Abstract [en]

The binding strength of the Helicobacter pylori adhesin–receptor complex BabA-ABO/Lewis b has been analyzed by means of dynamic force pectroscopy. High-resolution measurements of rupture forces were performed in situ on single bacterial cells, expressing the high-affinity binding BabA adhesin, by the use of force measuring optical tweezers. The resulting force spectra revealed the mechanical properties of a single BabA–Leb bond. It was found that the bond is dominated by one single energy barrier and that it is a slipbond. The bond length and thermal off-rate were assessed to be 0.86±0.07 nm and 0.015±0.006 s−1, respectively.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2009
Keywords
Optical tweezers, Single bond dissociation, Receptor–ligand interaction, Bond strength, Lewis b receptor
National Category
Physical Sciences Biochemistry and Molecular Biology
Research subject
Physics
Identifiers
urn:nbn:se:umu:diva-21486 (URN)10.1016/j.bpc.2009.03.007 (DOI)000267006000012 ()
External cooperation:
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
Björnham, O. & Schedin, S. (2009). Methods and error estimations of uncertainties in single-molecule dynamic force spectroscopy. European Biophysics Journal, 38(7), 911-922
Open this publication in new window or tab >>Methods and error estimations of uncertainties in single-molecule dynamic force spectroscopy
2009 (English)In: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 38, no 7, p. 911-922Article in journal (Refereed) Published
Abstract [en]

In dynamic force spectroscopy, access to the characteristic parameters of single molecular bonds requires non-trivial measurements and data processing as the rupture forces are found not only to be distributed over a wide range, but are also dependent on the loading rate. The choice of measurement procedure and data processing methods has a considerable impact on the accuracy and precision of the final results. We analyse, by means of numerical simulations, methods to minimize and assess the magnitude of the expected errors for different combinations of experimental and evaluation methods. It was found that the choice of fitting function is crucial to extract correct parameter values. Applying a Gaussian function, which is a common practice, is equivalent to introducing a systematic error, and leads to a consequent overestimation of the thermal off-rate by more than 30%. We found that the precision of the bond length and the thermal off-rate, in presence of unbiased noise, were improved by reducing the number of loading rates for a given number of measurements. Finally, the results suggest that the minimum number of measurements needed to obtain the bond strength, with acceptable precision, exceeds the common number of ~100 reported in literature.

 

Keywords
Specific Binding, DFS, Receptor-ligand, Error Propagation, Bond Length, Thermal off-rate, Monte Carlo Simulation
National Category
Other Physics Topics
Research subject
Physics
Identifiers
urn:nbn:se:umu:diva-21485 (URN)10.1007/s00249-009-0471-8 (DOI)000269055500009 ()
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
Björnham, O. & Axner, O. (2009). Multipili Attachment of Bacteria with Helix–like Pili Exposed to Stress. Journal of Chemical Physics, 130, 235102
Open this publication in new window or tab >>Multipili Attachment of Bacteria with Helix–like Pili Exposed to Stress
2009 (English)In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 130, p. 235102-Article in journal (Refereed) Published
Abstract [en]

A number of biomechanical properties of various types of pili expressed by Escherichia coli, predominantly their force–vs.–elongation behavior, have previously been assessed in detail on a single pilus level. In vivo, however, bacteria bind in general to host cells by a multitude of pili, which presumably provides them with adhesion properties that differs from those of single pili. Based upon the previously assessed biomechanical properties of individual pili, this work presents a theoretical analysis of the adhesion properties of multipili–attaching bacteria expressing helix–like pili exposed to an external force. Expressions for the adhesion lifetime of dual– and multipili–attaching bacteria are derived and their validity is verified by Monte Carlo simulations. It is shown that the adhesion lifetime of a multipili–binding bacterium depends to a large degree on the cooperativity of the attaching pili, which, in turn, depends strongly on their internal biomechanical properties, in particular their helix–like structure and its ability to elongate, which, in turn, depend on the intrinsic properties of the bonds, e.g. their lengths and activation energies. It is shown, for example, that a decrease in the length of a layer–to–layer bond in the rod of P pili, expressed by E. coli, by 50 % leads to a decrease in the adhesion lifetime of a bacterium attaching by 10 pili and exposed to a force of 500 pN by three orders of magnitude. The results indicate moreover that the intrinsic properties of the rod for this particular type of pili are optimized for multipili attachment under a broad range of external forces and presumably also to its in vivo environment. Even though the results presented in this work apply quantitatively to one type of pilus, they are assumed to apply qualitatively to all helix–like pili systems expressing slip bonds.

Identifiers
urn:nbn:se:umu:diva-21490 (URN)10.1063/1.3148027 (DOI)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09
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