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Strömberg, Nicklas
Publications (10 of 28) Show all publications
Barman, M., Murray, F., Bernardi, A. I., Broberg, K., Bölte, S., Hesselmar, B., . . . Sandin, A. (2018). Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden. BMJ Open, 8(10), Article ID e022013.
Open this publication in new window or tab >>Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden
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2018 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, no 10, article id e022013Article in journal (Refereed) Published
Abstract [en]

Introduction Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, 'Nutritional impact on Immunological maturation during Childhood in relation to the Environment' (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures-diet, microbes and environmental toxicants-during pregnancy and early childhood, on the maturation of the infant's immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health. Methods and analysis The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015-2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health. Ethics and dissemination The NICE cohort has been approved by the Regional Ethical Review Board in Umea, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-155656 (URN)10.1136/bmjopen-2018-022013 (DOI)000454739500070 ()30344169 (PubMedID)
Available from: 2019-01-25 Created: 2019-01-25 Last updated: 2019-01-25Bibliographically approved
Strömberg, N., Esberg, A., Sheng, N., Mårell, L., Löfgren-Burström, A., Danielsson, K. & Källestål, C. (2017). Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2. EBioMedicine, 26, 38-46
Open this publication in new window or tab >>Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2
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2017 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 26, p. 38-46Article in journal (Refereed) Published
Abstract [en]

Dental caries is a chronic infectious disease that affects billions of people with large individual differences in activity. We investigated whether PRH1 and PRH2 polymorphisms in saliva acidic proline-rich protein (PRP) receptors for indigenous bacteria match and predict individual differences in the development of caries. PRH1 and PRH2 variation and adhesion of indigenous and cariogenic (Streptococcus mutans) model bacteria were measured in 452 12-year-old Swedish children along with traditional risk factors and related to caries at baseline and after 5-years. The children grouped into low-to-moderate and high susceptibility phenotypes for caries based on allelic PRH1, PRH2 variation. The low-to-moderate susceptibility children (P1 and P4a-) experienced caries from eating sugar or bad oral hygiene or infection by S. mutans. The high susceptibility P4a (Db, PIF, PRP12) children had more caries despite receiving extra prevention and irrespective of eating sugar or bad oral hygiene or S. mutans-infection. They instead developed 3.9-fold more caries than P1 children from plaque accumulation in general when treated with orthodontic multibrackets; and had basic PRP polymorphisms and low DMBT1-mediated S. mutans adhesion as additional susceptibility traits. The present findings thus suggest genetic autoimmune-like (P4a) and traditional life style (P1) caries, providing a rationale for individualized oral care.

Keywords
Acidic proline-rich proteins, Chronic infections, Dental caries, Host susceptibility, PRH1, PRH2
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-143131 (URN)10.1016/j.ebiom.2017.11.019 (DOI)29191562 (PubMedID)
Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2018-06-09Bibliographically 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
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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
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
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2017 (English)In: EBioMedicine, ISSN 0360-0637, 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)
Funder
Swedish Research Council, 10906
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2018-06-09Bibliographically approved
Esberg, A., Löfgren-Burström, A., Öhman, U. & Strömberg, N. (2012). Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts. Infection and Immunity, 80(11), 3869-3879
Open this publication in new window or tab >>Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts
2012 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 11, p. 3869-3879Article in journal (Refereed) Published
Abstract [en]

The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r(2) = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B-1, and B-2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B-1 and B-2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously.

Place, publisher, year, edition, pages
Washington: American Society Microbiology, 2012
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-61766 (URN)10.1128/IAI.00435-12 (DOI)000309971600015 ()
Available from: 2012-11-27 Created: 2012-11-26 Last updated: 2018-06-08Bibliographically approved
Persson, K., Esberg, A., Claesson, R. & Strömberg, N. (2012). The pilin protein FimP from Actinomyces oris: crystal structure and sequence analyses. PLoS ONE, 7(10), e48364
Open this publication in new window or tab >>The pilin protein FimP from Actinomyces oris: crystal structure and sequence analyses
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, p. e48364-Article in journal (Refereed) Published
Abstract [en]

The Actinomyces oris type-1 pili are important for the initial formation of dental plaque by binding to salivary proteins that adhere to the tooth surface. Here we present the X-ray structure of FimP, the protein that is polymerized into the type-1 pilus stalk, assisted by a pili-specific sortase. FimP consists of three tandem IgG-like domains. The middle and C-terminal domains contain one autocatalyzed intramolecular isopeptide bond each, a feature used by Gram-positive bacteria for stabilization of surface proteins. While the N-terminal domain harbours all the residues necessary for forming an isopeptide bond, no such bond is observed in the crystal structure of this unpolymerized form of FimP. The monomer is further stabilized by one disulfide bond each in the N- and C-terminal domains as well as by a metal-coordinated loop protruding from the C-terminal domain. A lysine, predicted to be crucial for FimP polymerization by covalent attachment to a threonine from another subunit, is located at the rim of a groove lined with conserved residues. The groove may function as a docking site for the sortase-FimP complex. We also present sequence analyses performed on the genes encoding FimP as well as the related FimA, obtained from clinical isolates.

Keywords
crystal structure, pili
National Category
Structural Biology Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-61474 (URN)10.1371/journal.pone.0048364 (DOI)
Funder
Swedish Research Council
Available from: 2012-11-15 Created: 2012-11-15 Last updated: 2018-06-08Bibliographically approved
Maddocks, S. E., Wright, C. J., Nobbs, A. H., Brittan, J. L., Franklin, L., Strömberg, N., . . . Jenkinson, H. F. (2011). Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation. Molecular Microbiology, 81(4), 1034-1049
Open this publication in new window or tab >>Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation
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2011 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 81, no 4, p. 1034-1049Article in journal (Refereed) Published
Abstract [en]

The streptococcal antigen I/II (AgI/II)-family polypeptides are cell wall-anchored adhesins expressed by most indigenous oral streptococci. Proteins sharing 30-40% overall amino acid sequence similarities with AgI/II-family proteins are also expressed by Streptococcus pyogenes. The S. pyogenes M28_Spy1325 polypeptide (designated AspA) displays an AgI/II primary structure, with alanine-rich (A) and prolinerich (P) repeats flanking a V region that is projected distal from the cell. In this study it is shown that AspA from serotype M28 S. pyogenes, when expressed on surrogate host Lactococcus lactis, confers binding to immobilized salivary agglutinin gp-340. This binding was blocked by antibodies to the AspA-VP region. In contrast, the N-terminal region of AspA was deficient in binding fluid-phase gp-340, and L. lactis cells expressing AspA were not agglutinated by gp-340. Deletion of the aspA gene from two different M28 strains of S. pyogenes abrogated their abilities to form biofilms on saliva-coated surfaces. In each mutant strain, biofilm formation was restored by trans complementation of the aspA deletion. In addition, expression of AspA protein on the surface of L. lactis conferred biofilm-forming ability. Taken collectively, the results provide evidence that AspA is a biofilm-associated adhesin that may function in host colonization by S. pyogenes.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-104831 (URN)10.1111/j.1365-2958.2011.07749.x (DOI)000293752500015 ()21736640 (PubMedID)
Available from: 2015-06-17 Created: 2015-06-15 Last updated: 2018-06-07Bibliographically approved
Nordlund, Å., Johansson, I., Källestål, C., Ericson, T., Sjöström, M. & Strömberg, N. (2009). Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling. BMC Oral Health, 9(28)
Open this publication in new window or tab >>Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling
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2009 (English)In: BMC Oral Health, ISSN 1472-6831, E-ISSN 1472-6831, Vol. 9, no 28Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n=88) for ability to predict caries in a cross-sectional (baseline caries) and prospective (2-year caries development) setting. METHODS: Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces. RESULTS: A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n=18) predicted baseline caries better (ROC area 0.96) than five markers (0.92) and a single lactobacilli marker (0.7) with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n=18) explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76). By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88), or together with biological multimarkers (0.94), increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick. CONCLUSION: Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.

Place, publisher, year, edition, pages
BioMed Central, 2009
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-27771 (URN)10.1186/1472-6831-9-28 (DOI)19886991 (PubMedID)
Available from: 2009-11-19 Created: 2009-11-19 Last updated: 2018-06-08Bibliographically approved
Loimaranta, V., Hytönen, J., Pulliainen, A. T., Sharma, A., Tenovuo, J., Strömberg, N. & Finne, J. (2009). Leucine-rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor gp340.. Journal of Biological Chemistry, 284(28), 18614-23
Open this publication in new window or tab >>Leucine-rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor gp340.
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2009 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 284, no 28, p. 18614-23Article in journal (Refereed) Published
Abstract [en]

Scavenger receptors are innate immune molecules recognizing and inducing the clearance of non-host as well as modified host molecules. To recognize a wide pattern of invading microbes, many scavenger receptors bind to common pathogen-associated molecular patterns, such as lipopolysaccharides and lipoteichoic acids. Similarly, the gp340/DMBT1 protein, a member of the human scavenger receptor cysteine-rich protein family, displays a wide ligand repertoire. The peptide motif VEVLXXXXW derived from its scavenger receptor cysteine-rich domains is involved in some of these interactions, but most of the recognition mechanisms are unknown. In this study, we used mass spectrometry sequencing, gene inactivation, and recombinant proteins to identify Streptococcus pyogenes protein Spy0843 as a recognition receptor of gp340. Antibodies against Spy0843 are shown to protect against S. pyogenes infection, but no function or host receptor have been identified for the protein. Spy0843 belongs to the leucine-rich repeat (Lrr) family of eukaryotic and prokaryotic proteins. Experiments with truncated forms of the recombinant proteins confirmed that the Lrr region is needed in the binding of Spy0843 to gp340. The same motif of two other Lrr proteins, LrrG from the Gram-positive S. agalactiae and BspA from the Gram-negative Tannerella forsythia, also mediated binding to gp340. Moreover, inhibition of Spy0843 binding occurred with peptides containing the VEVLXXXXW motif, but also peptides devoid of the XXXXW motif inhibited binding of Lrr proteins. These results thus suggest that the conserved Lrr motif in bacterial proteins serves as a novel pattern recognition motif for unique core peptides of human scavenger receptor gp340.

Identifiers
urn:nbn:se:umu:diva-31886 (URN)10.1074/jbc.M900581200 (DOI)19465482 (PubMedID)
Available from: 2010-02-21 Created: 2010-02-21 Last updated: 2018-06-08
Jonasson, A., Eriksson, C., Jenkinson, H., Källestål, C., Johansson, I. & Strömberg, N. (2007). Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries. BMC Infectious Diseases, 11(7), 57
Open this publication in new window or tab >>Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries
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2007 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 11, no 7, p. 57-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries), harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. METHODS: A case-referent study was performed in 12-year-old Swedish children with high (n = 19) or low (n = 19) caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS) multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. RESULTS: All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively). The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37) and saliva adhesion of S. mutans Ingbritt (VIP = 1.47). The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc) compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. CONCLUSION: Gp-340 I behaves as a caries susceptibility protein.

Identifiers
urn:nbn:se:umu:diva-17124 (URN)10.1186/1471-2334-7-57 (DOI)17562017 (PubMedID)
Available from: 2007-11-01 Created: 2007-11-01 Last updated: 2018-06-09Bibliographically approved
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