Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Boren, Thomas
Alternative names
Publications (10 of 78) Show all publications
Holubnycha, V., Husak, Y., Korniienko, V., Bolshanina, S., Tveresovska, O., Myronov, P., . . . Pogorielov, M. (2024). Antimicrobial activity of two different types of silver nanoparticles against wide range of pathogenic bacteria. Nanomaterials, 14(2), Article ID 137.
Open this publication in new window or tab >>Antimicrobial activity of two different types of silver nanoparticles against wide range of pathogenic bacteria
Show others...
2024 (English)In: Nanomaterials, E-ISSN 2079-4991, Vol. 14, no 2, article id 137Article in journal (Refereed) Published
Abstract [en]

The emergence of antibiotic-resistant bacteria, particularly the most hazardous pathogens, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE)-pathogens pose a significant threat to global health. Current antimicrobial therapies, including those targeting biofilms, have shown limited effectiveness against these superbugs. Nanoparticles, specifically silver nanoparticles (AgNPs), have emerged as a promising alternative for combating bacterial infections. In this study, two types of AgNPs with different physic-chemical properties were evaluated for their antimicrobial and antibiofilm activities against clinical ESKAPE strains. Two types of silver nanoparticles were assessed: spherical silver nanoparticles (AgNPs-1) and cubic-shaped silver nanoparticles (AgNPs-2). AgNPs-2, characterized by a cubic shape and higher surface-area-to-volume ratio, exhibited superior antimicrobial activity compared to spherical AgNPs-1. Both types of AgNPs demonstrated the ability to inhibit biofilm formation and disrupt established biofilms, leading to membrane damage and reduced viability of the bacteria. These findings highlight the potential of AgNPs as effective antibacterial agents against ESKAPE pathogens, emphasizing the importance of nanoparticle characteristics in determining their antimicrobial properties. Further research is warranted to explore the underlying mechanisms and optimize nanoparticle-based therapies for the management of infections caused by antibiotic-resistant bacteria.

Place, publisher, year, edition, pages
MDPI, 2024
Keywords
antibiofilm activity, antimicrobial activity, ESKAPE pathogens, silver nanoparticles
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-220311 (URN)10.3390/nano14020137 (DOI)001151533400001 ()2-s2.0-85183090925 (Scopus ID)
Funder
EU, Horizon Europe, 101086441
Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2024-02-13Bibliographically approved
Okoye, J. C., Holland, A., Pitoulias, M., Paschalis, V., Piddubnyi, A., Dufailu, O. A., . . . Soultanas, P. (2023). Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers. Frontiers in Microbiology, 14, Article ID 1146418.
Open this publication in new window or tab >>Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers
Show others...
2023 (English)In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 14, article id 1146418Article in journal (Refereed) Published
Abstract [en]

Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major outer membrane protein (MOMP) of C. jejuni NCTC11168 binds to the Lewis b (Leb) antigen on the gastrointestinal epithelia of host tissues and this interaction can be competitively inhibited by ferric quinate (QPLEX), a ferric chelate structurally similar to bacterial siderophores. We provide evidence that QPLEX competitively inhibits the MOMP-Leb interaction. Furthermore, we demonstrate that QPLEX can be used as a feed additive in broiler farming to significantly reduce C. jejuni colonization. Our results indicate that QPLEX can be a viable alternative to the preventative use of antibiotics in broiler farming to combat C. jejuni infections.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
broilers, Campylobacter, gastrointestinal, iron chelates, Lewis b (Leb) antigen, major outer membrane protein (MOMP)
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-206342 (URN)10.3389/fmicb.2023.1146418 (DOI)000955904900001 ()36970690 (PubMedID)2-s2.0-85150695884 (Scopus ID)
Available from: 2023-04-28 Created: 2023-04-28 Last updated: 2024-01-17Bibliographically approved
Reihill, M., Fournière, V., Cheallaigh, A. N., Olofsson Edlund, J., Miller, G. J., Boren, T., . . . Oscarson, S. (2023). Synthesis of a B-antigen hexasaccharide, a B-lewis b heptasaccharide and glycoconjugates thereof to investigate binding properties of helicobacter pylori. Chemistry - A European Journal, 29(16), Article ID e202203672.
Open this publication in new window or tab >>Synthesis of a B-antigen hexasaccharide, a B-lewis b heptasaccharide and glycoconjugates thereof to investigate binding properties of helicobacter pylori
Show others...
2023 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 29, no 16, article id e202203672Article in journal (Refereed) Published
Abstract [en]

Infecting the stomach of almost 50 % of people, Helicobacter pylori is a causative agent of gastritis, peptic ulcers and stomach cancers. Interactions between bacterial membrane-bound lectin, Blood group Antigen Binding Adhesin (BabA), and human blood group antigens are key in the initiation of infection. Herein, the synthesis of a B-antigen hexasaccharide (B6) and a B-Lewis b heptasaccharide (BLeb7) and Bovine Serum Albumin glycoconjugates thereof is reported to assess the binding properties and preferences of BabA from different strains. From a previously reported trisaccharide acceptor a versatile key Lacto-N-tetraose tetrasaccharide intermediate was synthesized, which allowed us to explore various routes to the final targets, either via initial introduction of fucosyl residues followed by introduction of the B-determinant or vice versa. The first approach proved unsuccessful, whereas the second afforded the target structures in good yields. Protein conjugation using isothiocyanate methodology allowed us to reach high glycan loadings (up to 23 per protein) to mimic multivalent displays encountered in Nature. Protein glycoconjugate inhibition binding studies were performed with H. pylori strains displaying high or low affinity for Lewis b hexasaccharide structures showing that the binding to the high affinity strain was reduced due to the presence of the B-determinant in the Bleb7-conjugates and further reduced by the absence of the Lewis fucose residue in the B6-conjugate.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2023
Keywords
B antigen, B-Lewis b, glycoconjugate, synthesis, thioglycoside
National Category
Organic Chemistry
Identifiers
urn:nbn:se:umu:diva-205198 (URN)10.1002/chem.202203672 (DOI)000932377100001 ()36562295 (PubMedID)2-s2.0-85147992982 (Scopus ID)
Funder
Swedish Research Council, 2017-02183Swedish Cancer Society, 2018/807Swedish Cancer Society, 21/1875
Available from: 2023-02-28 Created: 2023-02-28 Last updated: 2023-07-14Bibliographically approved
Sharova, O., Smiyan, O. & Borén, T. (2021). Immunological effects of cerebral palsy and rehabilitation exercises in children. Brain, Behavior, and Immunity - Health, 18, Article ID 100365.
Open this publication in new window or tab >>Immunological effects of cerebral palsy and rehabilitation exercises in children
2021 (English)In: Brain, Behavior, and Immunity - Health, E-ISSN 2666-3546, Vol. 18, article id 100365Article in journal (Refereed) Published
Abstract [en]

Cerebral palsy (CP) is a group of motor disorders caused by non-progressive lesions of the premature brain with lifelong pathophysiological consequences that include dysregulation of innate immunity. Persistent inflammation with increased levels of circulating pro-inflammatory tumor necrosis factor alpha (TNF-a) is negatively associated with rehabilitation outcome in children with CP. Because of the crosstalk between innate and adaptive immunity, we investigated the effect of CP and rehabilitation exercises on the adaptive immune system in children with CP by measuring the levels of CD3+, CD4+, CD8+ Т-cells, and CD22+ B-cells and the levels of immunoglobulins. Children with CP had higher levels of CD3+, CD4+, CD8+ Т-cells, and CD22+ B-cells compared to healthy children, and the rehabilitation exercise programs produced better outcomes in terms of increased gains in motor function at an earlier age. Rehabilitation exercises performed over a month resulted in significantly decreased levels of IgA in serum and reduced numbers of B-lymphocytes and reduced IgM levels. Our study suggests that rehabilitation programs with a focus on neuroplasticity and physical exercises in children with CP can reduce both cellular and humoral immune responses.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
CD22+ B-cells, Children with cerebral palsy, IgA, Rehabilitation, T-cells, TNF-a
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-202965 (URN)10.1016/j.bbih.2021.100365 (DOI)34704080 (PubMedID)2-s2.0-85130868547 (Scopus ID)
Available from: 2023-01-14 Created: 2023-01-14 Last updated: 2023-01-14Bibliographically approved
Mthembu, Y. H., Jin, C., Padra, M., Liu, J., Olofsson Edlund, J., Ma, H., . . . Holgersson, J. (2020). Recombinant mucin-type proteins carrying LacdiNAc on different O-glycan core chains fail to support H. pylori binding.. Molecular Omics, 16(3), 243-257
Open this publication in new window or tab >>Recombinant mucin-type proteins carrying LacdiNAc on different O-glycan core chains fail to support H. pylori binding.
Show others...
2020 (English)In: Molecular Omics, E-ISSN 2515-4184, Vol. 16, no 3, p. 243-257Article in journal (Refereed) Published
Abstract [en]

The β4-N-acetylgalactosaminyltransferase 3 (B4GALNT3) transfers GalNAc in a β1,4-linkage to GlcNAc forming the LacdiNAc (LDN) determinant on oligosaccharides. The LacdiNAc-binding adhesin (LabA) has been suggested to mediate attachment of Helicobacter pylori to the gastric mucosa via binding to the LDN determinant. The O-glycan core chain specificity of B4GALNT3 is poorly defined. We investigated the specificity of B4GALNT3 on GlcNAc residues carried by O-glycan core 2, core 3 and extended core 1 precursors using transient transfection of CHO-K1 cells and a mucin-type immunoglobulin fusion protein as reporter protein. Binding of the LabA-positive H. pylori J99 and 26695 strains to mucin fusion proteins carrying the LDN determinant on different O-glycan core chains and human gastric mucins with and without LDN was assessed in a microtiter well-based binding assay, while the binding of 125I-LDN-BSA to various clinical H. pylori isolates was assessed in solution. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and western blotting confirmed the requirement of a terminal GlcNAc for B4GALNT3 activity. B4GALNT3 added a β1,4-linked GalNAc to GlcNAc irrespective of whether the latter was carried by a core 2, core 3 or extended core 1 chain. No LDN-mediated adhesion of H. pylori strains 26 695 and J99 to LDN determinants on gastric mucins or a mucin-type fusion protein carrying core 2, 3 and extended core 1 O-glycans were detected in a microtiter well-based adhesion assay and no binding of a 125I-labelled LDN-BSA neoglycoconjugate to clinical H. pylori isolates was identified.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2020
National Category
Basic Medicine Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-171214 (URN)10.1039/c9mo00175a (DOI)000542588800005 ()32267274 (PubMedID)2-s2.0-85086515284 (Scopus ID)
Available from: 2020-05-28 Created: 2020-05-28 Last updated: 2023-03-24Bibliographically approved
Jin, C., Barone, A., Boren, T. & Sandberg, S. (2018). Helicobacter pylori-binding nonacid glycosphingolipids in the human stomach. Journal of Biological Chemistry, 293(44), 17248-17266
Open this publication in new window or tab >>Helicobacter pylori-binding nonacid glycosphingolipids in the human stomach
2018 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 44, p. 17248-17266Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori has a number of well-characterized carbohydrate-binding adhesins (BabA, SabA, and LabA) that promote adhesion to the gastric mucosa. In contrast, information on the glycoconjugates present in the human stomach remains unavailable. Here, we used MS and binding of carbohydrate-recognizing ligands to characterize the glycosphingolipids of three human stomachs from individuals with different blood group phenotypes (O(Rh-)P, A(Rh+)P, and A(Rh+)p), focusing on compounds recognized by H. pylori. We observed a high degree of structural complexity, and the composition of glycosphingolipids differed among individuals with different blood groups. The type 2 chain was the dominating core chain of the complex glycosphingolipids in the human stomach, in contrast to the complex glycosphingolipids in the human small intestine, which have mainly a type 1 core. H. pylori did not bind to the O(Rh-)P stomach glycosphingolipids, whose major complex glycosphingolipids were neolactotetraosylceramide, the Lex, Lea, and H type 2 pentaosylceramides, and the Ley hexaosylceramide. Several H. pylori-binding compounds were present among the A(Rh+)P and A(Rh+)p stomach glycosphingolipids. Ligands for BabA-mediated binding of H. pylori were the Leb hexaosylceramide, the H type 1 pentaosylceramide, and the A type 1/ALeb heptaosylceramide. Additional H. pylori-binding glycosphingolipids recognized by BabA-deficient strains were lactosylceramide, lactotetraosylceramide, the x2 pentaosylceramide, and neolactohexaosylceramide. Our characterization of human gastric receptors required for H. pylori adhesion provides a basis for the development of specific compounds that inhibit the binding of this bacterium to the human gastric mucosa.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2018
Keywords
Helicobacter pylori, mass spectrometry (MS), glycolipid structure, adhesin, carbohydrate structure, ycoconjugate, virulence factor, gastric mucosa, glycosphingolipid characterization, H, pylori BabA hesin, Human gastric glycosphingolipids, microbial adhesion
National Category
Biochemistry and Molecular Biology Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-153648 (URN)10.1074/jbc.RA118.004854 (DOI)000449466500024 ()30232154 (PubMedID)2-s2.0-85056031487 (Scopus ID)
Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2023-03-24Bibliographically approved
Hansen, L. M., Gideonsson, P., Canfield, D. R., Borén, T. & Solnick, J. V. (2017). Dynamic Expression of the BabA Adhesin and Its BabB Paralog during Helicobacter pylori Infection in Rhesus Macaques. Infection and Immunity, 85(6), Article ID e00094.
Open this publication in new window or tab >>Dynamic Expression of the BabA Adhesin and Its BabB Paralog during Helicobacter pylori Infection in Rhesus Macaques
Show others...
2017 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 85, no 6, article id e00094Article in journal (Refereed) Published
Abstract [en]

Most Helicobacter pylori strains express the BabA adhesin, which binds to ABO/Leb blood group antigens on gastric mucin and epithelial cells and is found more commonly in strains that cause peptic ulcers or gastric cancer, rather than asymptomatic infection. We and others have previously reported that in mice, gerbils, and rhesus macaques, expression of babA is lost, either by phase variation or by gene conversion, in which the babB paralog recombines into the babA locus. The functional significance of loss of babA expression is unknown. Here we report that in rhesus monkeys, there is independent selective pressure for loss of babA and for overexpression of BabB, which confers a fitness advantage. Surprisingly, loss of babA by phase variation or gene conversion is not dependent on the capacity of BabA protein to bind Leb, which suggests that it may have other, unrecognized functions. These findings have implications for the role of outer membrane protein diversity in persistent H. pylori infection.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY, 2017
Keywords
Helicobacter pylori, adhesin, babA, rhesus
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-138236 (URN)10.1128/IAI.00094-17 (DOI)000405937200005 ()2-s2.0-85019885432 (Scopus ID)
Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2023-03-23Bibliographically approved
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
Show others...
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)2-s2.0-85014795847 (Scopus ID)
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2023-03-24Bibliographically approved
Kable, M. E., Hansen, L. M., Styer, C. M., Deck, S. L., Rakhimova, O., Shevtsova, A., . . . Solnick, J. V. (2017). Host Determinants of Expression of the Helicobacter pylori BabA Adhesin. Scientific Reports, 7, Article ID 46499.
Open this publication in new window or tab >>Host Determinants of Expression of the Helicobacter pylori BabA Adhesin
Show others...
2017 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 46499Article in journal (Refereed) Published
Abstract [en]

Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2-/- mice that do not have functional B or T cells, and in MyD88-/-, TLR2-/- and TLR4-/- mice that are defective in toll like receptor signaling. The presence of other bacteria had no effect on BabA expression as shown by infection of germ free mice. Moreover, loss of BabA expression was not dependent on Le(b) expression or the capacity of BabA to bind Leb. Surprisingly, gender was the host determinant most associated with loss of BabA expression, which was maintained to a greater extent in male mice and was associated with greater bacterial load. These results suggest the possibility that loss of BabA expression is not driven by adaptive immunity or toll-like receptor signaling, and that BabA may have other, unrecognized functions in addition to serving as an adhesin that binds Le(b).

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-134722 (URN)10.1038/srep46499 (DOI)000399367000001 ()28418004 (PubMedID)2-s2.0-85017633268 (Scopus ID)
Available from: 2017-05-19 Created: 2017-05-19 Last updated: 2023-03-24Bibliographically approved
Esberg, A., Sheng, N., Mårell, L., Claesson, R., Persson, K., Borén, T. & Strömberg, N. (2017). Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development. EBioMedicine, 24, 205-215
Open this publication in new window or tab >>Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development
Show others...
2017 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 24, p. 205-215Article in journal (Refereed) Published
Abstract [en]

Dental caries, which affects billions of people, is a chronic infectious disease that involves Streptococcus mutans, which is nevertheless a poor predictor of individual caries development. We therefore investigated if adhesin types of S.mutans with sucrose-independent adhesion to host DMBT1 (i.e. SpaP A, B or C) and collagen (i.e. Cnm, Cbm) match and predict individual differences in caries development. The adhesin types were measured in whole saliva by qPCR in 452 12-year-old Swedish children and related to caries at baseline and prospectively at a 5-year follow-up. Strains isolated from the children were explored for genetic and phenotypic properties. The presence of SpaP B and Cnm subtypes coincided with increased 5-year caries increment, and their binding to DMBT1 and saliva correlated with individual caries scores. The SpaP B subtypes are enriched in amino acid substitutions that coincided with caries and binding and specify biotypes of S. mutans with increased acid tolerance. The findings reveal adhesin subtypes of S. mutans that match and predict individual differences in caries development and provide a rationale for individualized oral care.

Keywords
Adhesion, Chronic infections, Dental caries, SpaP, Streptococcus mutans, Virulence
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-140203 (URN)10.1016/j.ebiom.2017.09.027 (DOI)000414392900033 ()28958656 (PubMedID)2-s2.0-85029795020 (Scopus ID)
Funder
Swedish Research Council, 10906
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2023-05-22Bibliographically approved
Organisations

Search in DiVA

Show all publications