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  • Paino, Annamari; Ahlstrand, Tuuli; Nuutila, Jari; Navickaite, Indre; Lahti, Maria; Tuominen, Heidi; Välimaa, Hannamari; Lamminmaki, Urpo; Pollanen, Marja T.; Ihalin, Riikka (2013)
  • Liljestrand, John M.; Paju, Susanna; Pietiäinen, Milla; Buhlin, Kåre; Persson, G. Rutger; Nieminen, Markku S.; Sinisalo, Juha; Mäntylä, Päivi; Pussinen, Pirkko J. (2018)
  • Ahlstrand, Tuuli; Torittu, Annamari; Elovaara, Heli; Välimaa, Hannamari; Pöllänen, Marja T.; Kasvandik, Sergo; Högbom, Martin; Ihalin, Riikka (2018)
    Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43nM in static settings and 2.4M in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested -lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.
  • Leskelä, Jaakko; Pietiäinen, Milla; Safer, Anton; Lehto, Markku; Metso, Jari; Malle, Ernst; Buggle, Florian; Becher, Heiko; Sundvall, Jouko; Grau, Armin; Pussinen, Pirkko J.; Palm, Frederick (2020)
    Introduction Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated. Materials and methods The assay to measure LPS-NC was set up by spiking serum samples with E. coli LPS. The LPS-NC, LPS-binding protein (LBP), soluble CD14 (sCD14), lipoprotein profiles, apo(lipoprotein) A-I, apoB, and phospholipid transfer protein (PLTP) activity, were determined in 98 ischemic stroke patients and 100 age- and sex-matched controls. Serum and saliva immune response to A. actinomycetemcomitans, its concentration in saliva, and serotype-distribution were examined. Results LPS-NC values ranged between 51-83% in the whole population. Although several of the LPS-NC determinants differed significantly between cases and controls (PLTP, sCD14, apoA-I, HDL-cholesterol), the levels did not (p = 0.056). The main determinants of LPS-NC were i) triglycerides (beta = -0.68, p Conclusion Serum LPS-NC comprised low PLTP-activity, triglyceride and LDL cholesterol concentrations, as well as high HDL cholesterol and IgG against A. actinomycetemcomitans. The present findings let us to conclude that LPS-NC did not associate with stroke.
  • Hyvärinen, Kati; Tuomainen, Anita M.; Laitinen, Saara; Alfthan, Georg; Salminen, Irma; Leinonen, Maija; Saikku, Pekka; Kovanen, Petri T.; Jauhiainen, Matti; Pussinen, Pirkko J. (2013)