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  • 1.
    Bugaytsova, Jeanna A.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Björnham, Oscar
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Swedish Defence Research Agency, 906 21 Umeå, Sweden.
    Chernov, Yevgen A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gideonsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Henriksson, Sara
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mendez, Melissa
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sjöström, Rolf
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mahdavi, Jafar
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. School of Life Sciences, CBS, University of Nottingham, NG7 2RD Nottingham, UK.
    Shevtsova, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ilver, Dag
    Moonens, Kristof
    Quintana-Hayashi, Macarena P.
    Moskalenko, Roman
    Aisenbrey, Christopher
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bylund, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Schmidt, Alexej
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Åberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Brännström, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Koeniger, Verena
    Vikström, Susanne
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Rakhimova, Lena
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ögren, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Liu, Hui
    Goldman, Matthew D.
    Whitmire, Jeannette M.
    Åden, Jörgen
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Younson, Justine
    Kelly, Charles G.
    Gilman, Robert H.
    Chowdhury, Abhijit
    Mukhopadhyay, Asish K.
    Nair, G. Balakrish
    Papadakos, Konstantinos S.
    Martinez-Gonzalez, Beatriz
    Sgouras, Dionyssios N.
    Engstrand, Lars
    Unemo, Magnus
    Danielsson, Dan
    Suerbaum, Sebastian
    Oscarson, Stefan
    Morozova-Roche, Ludmilla A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holgersson, Jan
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology.
    Landström, Maréne
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Eldridge, Angela M.
    Chromy, Brett A.
    Hansen, Lori M.
    Solnick, Jay V.
    Linden, Sara K.
    Haas, Rainer
    Dubois, Andre
    Merrell, D. Scott
    Schedin, Staffan
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Remaut, Han
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Berg, Douglas E.
    Boren, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence2017In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389Article in journal (Refereed)
    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.

  • 2.
    Bugaytsova, Jeanna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Chernov, Yevgen A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gideonsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mendez, Melissa
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Henriksson, Sara
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Mahdavi, Jafar
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. School of Life Sciences, CBS, University of Nottingham, Nottingham, UK..
    Quintana-Hayashi, Macarena
    Department of Biochemistry and Cell biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Shevtsova, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sjöström, Rolf
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Moskalenko, Roman
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of Pathology, Medical Institute, State University, Sumy, Ukraine.
    Aisenbrey, Christopher
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Université de Strasbourg, Institut de Chimie, Strasbourg, France.
    Moonens, Kristof
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Belgium.
    Björnham, Oscar
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. FOI Totalförsvarets Forskningsinstitut, Umeå, Sweden..
    Brännström, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Bylund, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Königer, Verena
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU, Munich, Germany.
    Vikström, Susanne
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Schmidt, Alexej
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Rakhimova, Lena
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ögren, Johan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ilver, Dag
    Department of Biochemistry and Cell biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Liu, Hui
    Department of Medicine, USUHS, Bethesda, MD, USA.
    Goldman, Matthew
    Department of Pediatrics, USUHS, Bethesda, MD, USA.
    Whitmire, Jeannette M
    Department of Microbiology and Immunology, USUHS, Bethesda, MD USA.
    Kelly, Charles G
    King's College London, Dental Institute, London, UK.
    Gilman, Robert H
    Department of International Health, John Hopkins School of Public Health, Baltimore, MD, USA.
    Chowdhury, Abhijit
    Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.
    Mukhopadhyay, Asish K
    Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
    Nair, Balakrish G
    Translational Health Science and Technology Institute, Haryana, India.
    Papadakos, Konstantinos S
    Hellenic Pasteur Institute, Athens, Greece.
    Martinez-Gonzalez, Beatriz
    Hellenic Pasteur Institute, Athens, Greece.
    Sgouras, Dionyssios N
    Hellenic Pasteur Institute, Athens, Greece.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Unemo, Magnus
    Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Danielsson, Dan
    Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sebastian, Suerbaum
    Institute for Medical Microbiology and Hospital Epidemiology Hannover Medical School, Hannover, Germany.
    Oscarson, Stefan
    Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland.
    Morozova-Roche, Ludmilla
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holgersson, Jan
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Eldridge, Angela
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.
    Chromy, Brett A
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.
    Hansen, Lori
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis, CA, USA.
    Solnick, Jay
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis, CA, USA.
    Haas, Rainer
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Schedin, Staffan
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Sara K
    Department of Biochemistry and Cell biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Dubois, Andre
    Department of Medicine, USUHS, Bethesda, MD, USA.
    Merrell, D. Scott
    Department of Microbiology and Immunology, USUHS, Bethesda, MD, USA.
    Remaut, Han
    Structural and Molecular Microbiology, VIB Department of Structural Biology, VIB, Brussels, Belgium.
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Berg, Douglas E
    Department of Medicine, University of California San Diego, La Jolla, CA, USA.
    Borén, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Acid Responsive Helicobacter pylori Adherence: Implications for Chronic Infection and DiseaseManuscript (preprint) (Other academic)
  • 3.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sjögren, Ulf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Brundin, Malin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Actinomyces radicidentis and Actinomyces haliotis, coccoid Actinomyces species isolated from the human oral cavity2017In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 48, p. 19-26Article in journal (Refereed)
    Abstract [en]

    There are few reports on the bacterial species Actinomyces radicidentis in the literature. In this study, putative A. radicidentis isolates were collected from 16 root canal samples from 601 examined patients. The isolates were examined by biochemical tests, 16S rRNA gene sequencing, Arbitrarily-primed (AP-) PCR, antibiotic susceptibility testing, and MALDI-TOF analyses. In parallel, two A. radicidentis reference strains and two putative A. radicidentis isolates from United Kingdom were tested. Sixteen of the 18 isolates were confirmed as A. radicidentis. The remaining two isolates, both of which were isolated from root canals (one from Sweden and the other from the UK), but were identified as Actinomyces haliotis by sequencing ∼ 1300 base pairs of the 16S rRNA-gene. This isolates had a divergent, but between them similar, AP-PCR pattern, and a common distribution of sequence signatures in the 16S rRNA gene, but were not identified by MALDI-TOF. A. haliotis is a close relative to A. radicidentis, hitherto only been described from a sea-snail. The identity of A. haliotis was confirmed by a phylogenetic tree based on 16S rRNA gene sequences with species specific sequences included, and by additional biochemical tests. The examined bacteria exhibited similar antibiotic susceptibility patterns when tested for 10 separate antibiotic classes with E-tests (bioMérieux). The MIC90 for β-lactams (benzylpenicillin and cefuroxime) and vancomycin was 0.5 mg/L, for colistin and ciprofloxacin 8 mg/mL and for the other antibiotic classes ≤ 25 mg/mL The isolation of A. haliotis from infected dental root canals cast doubt on the accepted opinion that all Actinomyces infections have an endogenous source.

  • 4. Cordova, R.
    et al.
    Knaze, V.
    Viallon, V.
    Rust, P.
    Schalkwijk, C. G.
    Weiderpass, E.
    Wagner, K-H.
    Mayen-Chacon, A-L.
    Aglago, E. K.
    Dahm, C. C.
    Overvad, K.
    Tjonneland, A.
    Halkjaer, J.
    Mancini, F. R.
    Boutron-Ruault, M-C.
    Fagherazzi, G.
    Katzke, V.
    Kuehn, T.
    Schulze, M. B.
    Boeing, H.
    Trichopoulou, A.
    Karakatsani, A.
    Thriskos, P.
    Masala, G.
    Krogh, V.
    Panico, S.
    Tumino, R.
    Ricceri, F.
    Spijkerman, A.
    Boer, J.
    Skeie, G.
    Rylander, C.
    Borch, K. B.
    Quiros, J. R.
    Agudo, A.
    Redondo-Sanchez, D.
    Amiano, P.
    Gomez-Gomez, J-H.
    Barricarte, A.
    Ramne, S.
    Sonestedt, E.
    Johansson, I.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Tong, T.
    Aune, D.
    Tsilidis, K. K.
    Gunter, M. J.
    Jenab, M.
    Freisling, Heinz
    Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults2019In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215Article in journal (Refereed)
    Abstract [en]

    Purpose: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up.

    Methods: A total of 255,170 participants aged 25–70 years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects.

    Results: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087–0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041–0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish.

    Conclusion: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

  • 5.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haworth, Simon
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Allelic Variation in Taste Genes Is Associated with Taste and Diet Preferences and Dental Caries2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 7, article id 1491Article in journal (Refereed)
    Abstract [en]

    Taste and diet preferences are complex and influenced by both environmental and host traits while affecting both food selection and associated health outcomes. The present study genotyped 94 single nucleotide polymorphisms (SNPs) in previously reported taste and food intake related genes and assessed associations with taste threshold (TT) and preferred intensity (PT) of sweet, sour and bitter, food preferences, habitual diet intake, and caries status in healthy young Swedish men and women (n = 127). Polymorphisms in the GNAT3, SLC2A4, TAS1R1 and TAS1R2 genes were associated with variation in TT and PT for sweet taste as well as sweet food intake. Increasing PT for sweet was associated with increasing preference and intake of sugary foods. Similarly, increasing TT for sour was associated with increasing intake of sour foods, whereas the associations between food preference/intake and TT/PT for bitter was weak in this study group. Finally, allelic variation in the GNAT3, SLC2A2, SLC2A4, TAS1R1 and TAS1R2 genes was associated with caries status, whereas TT, PT and food preferences were not. It was concluded that variations in taste receptor, glucose transporter and gustducin encoding genes are related to taste perception, food preference and intake as well as the sugar-dependent caries disease.

  • 6.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Microbial complexes and caries in 17-year-olds with and without Streptococcus mutans2018In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 97, no 3, p. 275-282Article in journal (Refereed)
    Abstract [en]

    Streptococcus mutans is a key bacterial species in the caries process, which affects >90% of the population worldwide. However, other acidogenic and aciduric/acidophilic species may contribute to disease development. In Sweden, a country with low prevalences of caries and S. mutans, a significant portion of caries-affected adolescents lack detectable levels of S. mutans. The objectives of the present study were 1) to characterize the tooth biofilm and saliva microbiota of adolescents with caries disease, with or without detectable S. mutans, from tooth biofilm and saliva samples and 2) to assess taxa clustering in the tooth biofilm and saliva samples and relate this information to caries status. For 17-y-old participants ( N = 154), enamel and dentin caries (the total number of present carious surfaces in the enamel and dentin) and caries experience (the number of decayed and filled tooth surfaces) were recorded, dental biofilm and saliva samples obtained, and information on medical and lifestyle habits collected. Multiplex 16S rDNA (V3-V4) sequencing of bacterial DNA was performed with the Illumina MiSeq platform. The Human Oral Microbiome Database and the ProbeSeq pipeline were used in the HOMI NGS procedure. In subjects with caries experience, high levels of S. mutans were associated with a few species and low levels with a panel of saccharolytic species. Present caries was similarly associated with a panel of saccharolytic species in subjects without S. mutans. Furthermore, tooth biofilm microbiota could be used to establish 4 clusters of subjects with different caries experiences. In particular, high levels of S. mutans were associated with the presence of a few influential species in multivariate modeling, including Scardovia wiggsiae. By contrast, a panel of less avid lactic acid-producing species was influential in patients with undetectable or low S. mutans levels in such modeling. These findings support a prominent role of S. mutans in infected adolescents but also the ecologic concept, especially in S. mutans-free subjects.

  • 7.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haworth, Simon
    Brunius, Carl
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 452Article in journal (Refereed)
    Abstract [en]

    Carbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.

  • 8.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Marcus J O
    Byström, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis.2006In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 24, no 1, p. 139-148Article in journal (Refereed)
    Abstract [en]

    The Saccharomyces cerevisiae Elongator complex consisting of the six Elp1-Elp6 proteins has been proposed to participate in three distinct cellular processes: transcriptional elongation, polarized exocytosis, and formation of modified wobble uridines in tRNA. Therefore it was important to clarify whether Elongator has three distinct functions or whether it regulates one key process that leads to multiple downstream effects. Here, we show that the phenotypes of Elongator-deficient cells linking the complex to transcription and exocytosis are suppressed by increased expression of two tRNA species. Elongator is required for formation of the mcm(5) group of the modified wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U) in these tRNAs. Hence, in cells with normal levels of these tRNAs, presence of mcm(5)s(2)U is crucial for posttranscriptional expression of gene products important in transcription and exocytosis. Our results indicate that the physiologically relevant function of the evolutionary-conserved Elongator complex is in formation of modified nucleosides in tRNAs.

  • 9.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Isehed, Catrine
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Periodontology, Public Dental Health County Council of Gävleborg, Gävle County Hospital, Gävle, Sweden; Center for Clinical Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    Holmlund, Anders
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Peri-implant crevicular fluid proteome before and after adjunctive enamel matrix derivative treatment of peri-implantitis2019In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 46, no 6, p. 669-677Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to explore which peri‐implant crevicular fluid (PICF) protein pattern is associated with the active peri‐implantitis process.

    Materials and methods: Peri‐implant crevicular fluid from 25 peri‐implantitis sites were subjected to proteomic analysis using liquid chromatography–tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between PICF protein pattern and implant loss, bleeding on probing, pocket depth and enamel matrix derivative (EMD) treatment.

    Results: Clustering of subjects based on their 3–12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 differentiated from cluster 3 by 52 proteins (R2 = 90%, Q2 = 80%) and belonging to cluster 2 was associated with implant loss (p = 0.009) and bleeding on probing (p = 0.001). Cluster 3 was associated with implant survival and EMD treatment (p = 0.044).

    Conclusion: Here, we demonstrate that a specific PICF proteomic profile associates with active peri‐implantitis process and implant loss.

  • 10.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Isehed, Catrine
    Umeå University, Faculty of Medicine, Department of Odontology. Folktandvården Gävleborg AB, Region Gävleborg.
    Holmlund, Anders
    Folktandvården Gävleborg AB, Region Gävleborg.
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    PICF proteome before and after adjunctive EMD treatment of peri-implantitisManuscript (preprint) (Other academic)
    Abstract [en]

    Aim: The aim of this study was to explore which peri-implant crevicular fluid (PICF) protein patter that are associated with the active peri-implantitis process.

    Materials and methods: PICF from 25 peri-implantitis sites were subjected to proteomic analysis using liquid chromatography-tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between protein expression and implant loss, radiographic bone level change, bleeding on probing, pocket depth, and enamel matrix derivative (EMD) treatment. 

    Results: Clustering of subjects based on their 3 to 12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 was differentiated from cluster 3 by 52 proteins (R2=90%, Q2=80%) and belonging to cluster 2 had an odds ratio for implant loss of 7.9 (95% confidence interval 1.8 to 35.9). Cluster 3 was related to implant survival (p=0.007) after 5 years and associated with EMD treatment (p=0.044). Furthermore, cluster 2 was associated with radiographic bone loss (p<0.0001) and bleeding on probing (p=0.001). 

    Conclusion: EMD treatment was associated with the PICF proteomic profile related to implant survival. EMD reduced number of proteins, dominated by proteins associated with implant loss. However, whether these effects are direct or indirect requires further exploration.

  • 11.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öhman, Ulla
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts2012In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 11, p. 3869-3879Article in journal (Refereed)
    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.

  • 12.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Moqtaderi, Zarmik
    Fan, Xiaochun
    Lu, Jian
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Struhl, Kevin
    Byström, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Iwr1 protein is important for preinitiation complex formation by all three nuclear RNA polymerases in Saccharomyces cerevisiae2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, p. e20829-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Iwr1, a protein conserved throughout eukaryotes, was originally identified by its physical interaction with RNA polymerase (Pol) II.

    PRINCIPAL FINDINGS: Here, we identify Iwr1 in a genetic screen designed to uncover proteins involved in Pol III transcription in S. cerevisiae. Iwr1 is important for Pol III transcription, because an iwr1 mutant strain shows reduced association of TBP and Pol III at Pol III promoters, a decreased rate of Pol III transcription, and lower steady-state levels of Pol III transcripts. Interestingly, an iwr1 mutant strain also displays reduced association of TBP to Pol I-transcribed genes and of both TBP and Pol II to Pol II-transcribed promoters. Despite this, rRNA and mRNA levels are virtually unaffected, suggesting a post-transcriptional mechanism compensating for the occupancy defect.

    CONCLUSIONS: Thus, Iwr1 plays an important role in preinitiation complex formation by all three nuclear RNA polymerases.

  • 13.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Muller, Ludo A. H.
    McCusker, John H.
    Genomic structure of and genome-wide recombination in the saccharomyces cerevisiae S288C progenitor isolate EM932011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 9, p. e25211-Article in journal (Refereed)
    Abstract [en]

    The diploid isolate EM93 is the main ancestor to the widely used Saccharomyces cerevisiae haploid laboratory strain, S288C. In this study, we generate a high-resolution overview of the genetic differences between EM93 and S288C. We show that EM93 is heterozygous for >45,000 polymorphisms, including large sequence polymorphisms, such as deletions and a Saccharomyces paradoxus introgression. We also find that many large sequence polymorphisms (LSPs) are associated with Ty-elements and sub-telomeric regions. We identified 2,965 genetic markers, which we then used to genotype 120 EM93 tetrads. In addition to deducing the structures of all EM93 chromosomes, we estimate that the average EM93 meiosis produces 144 detectable recombination events, consisting of 87 crossover and 31 non-crossover gene conversion events. Of the 50 polymorphisms showing the highest levels of non-crossover gene conversions, only three deviated from parity, all of which were near heterozygous LSPs. We find that non-telomeric heterozygous LSPs significantly reduce meiotic recombination in adjacent intervals, while sub-telomeric LSPs have no discernable effect on recombination. We identified 203 recombination hotspots, relatively few of which are hot for both non-crossover gene conversions and crossovers. Strikingly, we find that recombination hotspots show limited conservation. Some novel hotspots are found adjacent to heterozygous LSPs that eliminate other hotspots, suggesting that hotspots may appear and disappear relatively rapidly.

  • 14.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sheng, Nongfei
    Umeå University, Faculty of Medicine, Department of Odontology.
    Mårell, Lena
    Umeå University, Faculty of Medicine, Department of Odontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Persson, Karina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Borén, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology.
    Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development2017In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 24, p. 205-215Article in journal (Refereed)
    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.

  • 15. Huseinovic, Ena
    et al.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Winkvist, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Department of Internal Medicine and Clinical Nutrition, the Sahlgrenska Academy, University of Gothenburg, Sweden.
    Changes in food intake patterns during 2000–2007 and 2008–2016 in the population-based Northern Sweden Diet Database2019In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 18, article id 36Article in journal (Refereed)
    Abstract [en]

    Background: Food intake patterns provide a summary of dietary intake. Few studies have examined trends in food intake patterns over time in large, population-based studies. We examined food intake patterns and related sociodemographic and individual characteristics in the large Northern Sweden Diet Database during the two time windows 2000–2007 and 2008–2016.

    Methods: In total, 100 507 participants (51% women) who had filled in a 64-item food frequency questionnaire and provided background and sociodemographic data between 2000 and 2016 were included. Food intake patterns were evaluated for women and men separately for the two time windows 2000–2007 and 2008–2016, respectively. Latent class analysis was used to identify distinct, latent clusters based on 40 food groups.

    Results: Among both women and men, a greater proportion of participants were classified into food intake patterns characterized by high-fat spread and high-fat dairy during 2008–2016 compared to 2000–2007. In the earlier time window, these high-fat clusters were related to lower educational level and smoking. Simultaneously, the proportion of women and men classified into a cluster characterized by high intake of fruit, vegetables, and fibre decreased from the earlier to the later time window.

    Conclusion: From a public health perspective, the increase in clusters with a high conditional mean for high-fat spread and high-fat dairy and decrease in clusters with a high conditional mean for fruit and vegetables, during the time period 2008–2016 compared to 2000–2007, is worrisome as it indicates a shift away from the recommended food habits. Subgroups of women and men with less healthy dietary patterns in the time window 2008–2016 with lower education, lower age, higher body mass index, lower levels of physical activity and more smoking were identified and future interventions may be targeted towards these groups.

  • 16.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Eriksson, Linda
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haworth, Simon
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Self-reported bovine milk intake is associated with oral microbiota composition2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 3, article id e0193504Article in journal (Refereed)
    Abstract [en]

    Bovine milk intake has been associated with various disease outcomes, with modulation of the gastro-intestinal microbiome being suggested as one potential mechanism. The aim of the present study was to explore the oral microbiota in relation to variation in self-reported milk intake. Saliva and tooth biofilm microbiota was characterized by 16S rDNA sequencing, PCR and cultivation in 154 Swedish adolescents, and information on diet and other lifestyle markers were obtained from a questionnaire, and dental caries from clinical examination. A replication cohort of 31,571 adults with similar information on diet intake, other lifestyle markers and caries was also studied. Multivariate partial least squares (PLS) modelling separated adolescents with low milk intake (lowest tertile with <0.4 servings/day) apart from those with high intake of milk (≥3.7 servings/day) based on saliva and tooth biofilm, respectively. Taxa in several genera contributed to this separation, and milk intake was inversely associated with the caries causing Streptococcus mutans in saliva and tooth biofilm samples by sequencing, PCR and cultivation. Despite the difference in S. mutans colonization, caries prevalence did not differ between milk consumption groups in the adolescents or the adults in the replication cohort, which may reflect that a significant positive association between intake of milk and sweet products was present in both the study and replication group. It was concluded that high milk intake correlates with different oral microbiota and it is hypothesized that milk may confer similar effects in the gut. The study also illustrated that reduction of one single disease associated bacterial species, such as S. mutans by milk intake, may modulate but not prevent development of complex diseases, such as caries, due to adverse effects from other causal factors, such as sugar intake in the present study.

  • 17.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, 90187 Umeå, Sweden. .
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Winkvist, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden. .
    Dairy Product Intake and Cardiometabolic Diseases in Northern Sweden: A 33-Year Prospective Cohort Study2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 284Article in journal (Refereed)
    Abstract [en]

    Dairy products are important constituents of most diets, and their association with adverse health outcomes remains a focus. We characterized dairy food intake and examined associations with the incidence of type 2 diabetes (T2D), myocardial infarction (MI) or stroke among 108,065 Swedish men and women. Hazard ratios (HRs) and 95% CIs were estimated using the multivariable Cox proportional hazards models in a population characterized by high milk tolerance. During a mean follow-up of 14.2 years, 11,641 first-time events occurred. Non-fermented milk intake decreased, whereas butter intake increased over the period. For high intake of non-fermented milk, the HR (95% CI) for developing T2D and MI was 1.17 (1.03, 1.34) and 1.23 (1.10, 1.37), respectively, in men. A greater intake of butter, fermented milk, and cheese tended to be associated with a reduced risk of T2D and/or MI. Non-consumers and those who chose low-fat variants of the targeted dairy products had increased risk for T2D, MI, or stroke compared to those in the non-case group. Generally, effect-sizes were small. This prospective study found that non-fermented milk was associated with an increased risk for developing T2D and MI and that subjects abstaining from dairy products or choosing low-fat variants were at greater risk. However, the overall cardiometabolic risk of non-fermented milk intake was judged as low, since the effect sizes were small.

  • 18.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Winkvist, Anna
    Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population2018In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 17, article id 110Article in journal (Refereed)
    Abstract [en]

    Background: The association between milk and dairy intake and the incidence of cardiometabolic diseases, cancer and mortality has been evaluated in many studies, but these studies have had conflicting results with no clear conclusion on causal or confounding associations. The present study aims to further address this association by cross-sectional and longitudinal evaluation of the associations between exposure to various types of dairy products and metabolic risk markers among inhabitants in northern Sweden while taking other lifestyle factors into account.

    Methods: Respondents in the Vasterbotten Intervention Programme with complete and plausible diet data between 1991 and 2016 were included, yielding 124,934 observations from 90,512 unique subjects. For longitudinal analysis, 27,682 participants with a visit 8-12years after the first visit were identified. All participants completed a validated Food Frequency Questionnaire. Metabolic risk markers, including body mass index (BMI), blood pressure, serum (S) cholesterol and triglycerides, and blood glucose, were measured. Participants were categorized into quintiles by intake of dairy products, and risk (odds ratios, OR) of undesirable levels of metabolic risk markers was assessed in multivariable logistic regression analyses. In longitudinal analyses, intake quintiles were related to desirable levels of metabolic risk markers at both visits or deterioration at follow-up using Cox regression analyses.

    Results: The OR of being classified with an undesirable BMI decreased with increasing quintiles of total dairy, cheese and butter intake but increased with increasing non-fermented milk intake. The OR of being classified with an undesirable S-cholesterol level increased with increasing intake of total dairy, butter and high fat (3%) non-fermented milk, whereas an undesirable S-triglyceride level was inversely associated with cheese and butter intake in women. In longitudinal analyses, increasing butter intake was associated with deterioration of S-cholesterol and blood glucose levels, whereas increasing cheese intake was associated with a lower risk of deterioration of S-triglycerides.

    Conclusions: Confounding factors likely contribute to the demonstrated association between dairy intake and mortality, and other medical conditions and analyses should be stratified by dairy type.

  • 19.
    Johansson, Marcus J O
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Esberg, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Björk, Glenn R
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Byström, Anders S
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Eukaryotic wobble uridine modifications promote a functionally redundant decoding system.2008In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 28, no 10, p. 3301-3312Article in journal (Refereed)
    Abstract [en]

    The translational decoding properties of tRNAs are modulated by naturally occurring modifications of their nucleosides. Uridines located at the wobble position (nucleoside 34 [U34]) in eukaryotic cytoplasmic tRNAs often harbor a 5-methoxycarbonylmethyl (mcm(5)) or a 5-carbamoylmethyl (ncm(5)) side chain and sometimes an additional 2-thio (s2) or 2'-O-methyl group. Although a variety of models explaining the role of these modifications have been put forth, their in vivo functions have not been defined. In this study, we utilized recently characterized modification-deficient Saccharomyces cerevisiae cells to test the wobble rules in vivo. We show that mcm5 and ncm5 side chains promote decoding of G-ending codons and that concurrent mcm5 and s2 groups improve reading of both A- and G-ending codons. Moreover, the observation that the mcm5U34- and some ncm5U34-containing tRNAs efficiently read G-ending codons challenges the notion that eukaryotes do not use U-G wobbling.

  • 20.
    Lu, Jian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Esberg, Anders
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Byström, Anders
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Identification of determinants in tRNA required for Kluyveromyces lactis γ-toxin cleavageManuscript (Other academic)
  • 21. Lu, Jian
    et al.
    Esberg, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Byström, Anders S
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Kluyveromyces lactis γ-toxin, a ribonuclease that recognizes the anticodon stem loop of tRNA2008In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 36, no 4, p. 1072-1080Article in journal (Refereed)
    Abstract [en]

    Kluyveromyces lactis gamma-toxin is a tRNA endonuclease that cleaves Saccharomyces cerevisiae [see text] between position 34 and position 35. All three substrate tRNAs carry a 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U) residue at position 34 (wobble position) of which the mcm(5) group is required for efficient cleavage. However, the different cleavage efficiencies of mcm(5)s(2)U(34)-containing tRNAs suggest that additional features of these tRNAs affect cleavage. In the present study, we show that a stable anticodon stem and the anticodon loop are the minimal requirements for cleavage by gamma-toxin. A synthetic minihelix RNA corresponding to the anticodon stem loop (ASL) of the natural substrate [see text] is cleaved at the same position as the natural substrate. In [see text], the nucleotides U(34)U(35)C(36)A(37)C(38) are required for optimal gamma-toxin cleavage, whereas a purine at position 32 or a G in position 33 dramatically reduces the cleavage of the ASL. Comparing modified and partially modified forms of E. coli and yeast [see text] reinforced the strong stimulatory effects of the mcm(5) group, revealed a weak positive effect of the s(2) group and a negative effect of the bacterial 5-methylaminomethyl (mnm(5)) group. The data underscore the high specificity of this yeast tRNA toxin.

  • 22.
    Lu, Jian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Huang, Bo
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Esberg, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Johansson, Marcus J O
    Byström, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    The Kluyveromyces lactis γ-toxin targets tRNA anticodons.2005In: RNA: A publication of the RNA Society, ISSN 1355-8382, E-ISSN 1469-9001, Vol. 11, no 11, p. 1648-1654Article in journal (Refereed)
    Abstract [en]

    Kluyveromyces lactis killer strains secrete a heterotrimeric toxin (zymocin), which causes an irreversible growth arrest of sensitive yeast cells. Despite many efforts, the target(s) of the cytotoxic gamma-subunit of zymocin has remained elusive. Here we show that three tRNA species tRNA(Glu)(mcm(5)s(2)UUC), tRNA(Lys)(mcm(5)s(2)UUU), and tRNA(Gln)(mcm(5)s(2)UUG) are the targets of gamma-toxin. The toxin inhibits growth by cleaving these tRNAs at the 3' side of the modified wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U). Transfer RNA lacking a part of or the entire mcm(5) group is inefficiently cleaved by gamma-toxin, explaining the gamma-toxin resistance of the modification-deficient trm9, elp1-elp6, and kti11-kti13 mutants. The K. lactis gamma-toxin is the first eukaryotic toxin shown to target tRNA.

  • 23.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Winkvist, Anna
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Dairy Products and Cancer Risk in a Northern Sweden Population2019In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914Article in journal (Refereed)
    Abstract [en]

    The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5-Q1), 1.11; 95% CI, 0.97-1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5-Q1, 0.95; 95% CI, 0.88-1.04; Ptrend = 0.039), smoking-related (HR Q5-Q1, 0.84; 95% CI, 0.72-0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5-Q1, 0.82; 95% CI, 0.63-1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5-Q1, 0.91; 95% CI, 0.81-1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

  • 24.
    Persson, Karina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    The pilin protein FimP from Actinomyces oris: crystal structure and sequence analyses2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, p. e48364-Article in journal (Refereed)
    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.

  • 25.
    Strömberg, Nicklas
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sheng, Nongfei
    Umeå University, Faculty of Medicine, Department of Odontology.
    Mårell, Lena
    Umeå University, Faculty of Medicine, Department of Odontology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Odontology.
    Danielsson, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Källestål, Carina
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Women’s and Children’s Health/International Maternal and Child Health, Uppsala University, SE-751 85 Uppsala, Sweden.
    Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH22017In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 26, p. 38-46Article in journal (Refereed)
    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.

  • 26.
    Tükenmez, Hasan
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Xu, Hao
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Byström, Anders S.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes2015In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 43, no 19, p. 9489-9499Article in journal (Refereed)
    Abstract [en]

    In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U), 5-methoxycarbonylmethyluridine (mcm5U), 5-carbamoylmethyluridine (ncm5U) or 5-carbamoylmethyl-2′-O-methyluridine (ncm5Um) nucleosides in the anticodon at the wobble position (U34). Earlier we showed that mutants unable to form the side chain at position 5 (ncm5 or mcm5) or lacking sulphur at position 2 (s2) of U34 result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs. This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting. The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error. In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system. We here show that the presence of mcm5 and s2 side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors.

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