| 1. |
- Drobni, Mirva, et al.
(author)
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A host-derived pentapeptide enhancing host-bacteria commensalisms and communication
- 2006
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In: Infection and Immunity. - Washington : American society for microbiology. - 0019-9567 .- 1098-5522. ; 74:11, s. 6293-6299
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Journal article (peer-reviewed)abstract
- Salivary proline-rich proteins (PRPs) attach commensal Actinomyces and Streptococcus species to teeth. Here, gel filtration, mass spectrometry and Edman degradation were applied to show the release of a pentapeptide, RGRPQ, from PRP-1 upon proteolysis by Streptococcus gordond. Moreover, synthetic RGRPQ and derivatives were used to investigate associated innate properties and responsible motifs. The RGRPQ peptide increased 2.5-fold the growth rate of S. gordonii via a Q-dependent sequence motif and selectively stimulated oral colonization of this organism in a rat model in vivo. In contrast, the growth of Streptococcus mutans, implicated in caries, was not affected. While the entire RGRPQ sequence was required to block sucrose-induced pH-decrease by S. gordonii and S. mutans, the N-terminal Arg residue mediated the pH increase (i.e., ammonia production) by S. gordonii alone (which exhibits Arg catabolism to ammonia). Strains of commensal viridans streptococci exhibited PR-P degradation and Arg catabolism, whereas cariogenic species did not. The RGRPQ peptide mediated via a differential Q-dependent sequence motif, adhesion inhibition, and desorption of PRP-1-binding strains of A. naeslundii genospecies 2 (5 of 10 strains) but not of S. gordonii (n = 5). The inhibitable A. naeslundii strains alone displayed the same binding profile as S. gordond to hybrid peptides terminating in RGRPQ or GQSPQ, derived from the middle or C-terminal segments of PRP-1. The present findings indicate the presence of a host-bacterium interaction in which a host peptide released by bacterial proteolysis affects key properties in biofilm formation.
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| 2. |
- Drobni, Mirva, et al.
(author)
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Host-derived pentapeptide affecting adhesion, proliferation, and local pH in biofilm communities composed of Streptococcus and Actinomyces species.
- 2006
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:11, s. 6293-6299
-
Journal article (peer-reviewed)abstract
- Salivary proline-rich proteins (PRPs) attach commensal Actinomyces and Streptococcus species to teeth. Here, gel filtration, mass spectrometry and Edman degradation were applied to show the release of a pentapeptide, RGRPQ, from PRP-1 upon proteolysis by Streptococcus gordonii. Moreover, synthetic RGRPQ and derivatives were used to investigate associated innate properties and responsible motifs. The RGRPQ peptide increased 2.5-fold the growth rate of S. gordonii via a Q-dependent sequence motif and selectively stimulated oral colonization of this organism in a rat model in vivo. In contrast, the growth of Streptococcus mutans, implicated in caries, was not affected. While the entire RGRPQ sequence was required to block sucrose-induced pH-decrease by S. gordonii and S. mutans, the N-terminal Arg residue mediated the pH increase (i.e., ammonia production) by S. gordonii alone (which exhibits Arg catabolism to ammonia). Strains of commensal viridans streptococci exhibited PRP degradation and Arg catabolism, whereas cariogenic species did not. The RGRPQ peptide mediated via a differential Q-dependent sequence motif, adhesion inhibition, and desorption of PRP-1-binding strains of A. naeslundii genospecies 2 (5 of 10 strains) but not of S. gordonii (n=5). The inhibitable A. naeslundii strains alone displayed the same binding profile as S. gordonii to hybrid peptides terminating in RGRPQ or GQSPQ, derived from the middle or C-terminal segments of PRP-1. The present findings indicate the presence of a host-bacterium interaction in which a host peptide released by bacterial proteolysis affects key properties in biofilm formation.
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| 3. |
- Eriksson, Christer, et al.
(author)
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Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation
- 2007
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In: Glycoconjugate Journal. - : Springer Science and Business Media LLC. - 1573-4986 .- 0282-0080. ; 24:2-3, s. 131-142
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Journal article (peer-reviewed)abstract
- Glycoprotein gp-340 aggregates bacteria in saliva as part of innate defence at mucosal surfaces. We have detected size- and glycoforms of gp-340 between human saliva samples (n=7) and lung gp-340 from a proteinosis patient using antibodies and lectins in Western blots and ELISA measurements. Western blots of saliva samples, and of gp-340 purified, from the seven donors using a gp-340 specific antibody distinguished four gp-340 size variants, designated I to IV (n=2,2,2 and 1). While saliva gp-340 variants I to III had single bands of increasing sizes, variant IV and lung gp-340 had double bands. Purified I to IV proteins all revealed a N-terminal sequence TGGWIP upon Edman degradation. Moreover, purified gp-340 from the seven donors and lung gp-340 shared N-glycans, sialylated Gal beta 1-3GalNAc and (poly)lactosamine structures. However, the larger size gp-340 grouping II/III (n=4) and smaller size grouping I/IV correlated with a secretor, Se(+), and a non secretor, Se(-), dependent glycoform of gp-340, respectively (p=0.03). The Se(+) glycoforms contained ABH, Le(b), Le(y) and polylactosamine structures, while the Se(-) glycoforms lacked ABH antigens but expressed Lea, Lex and lactosamine structures. By contrast, lung gp- 340 completely lacked ABH, Le(a/b), Le(x/y) or sLe(x) structures. Gp-340 and secretor typing of saliva from additional donors (n=29) showed gp-340 glycoforms I to IV for 6, 16, 4 and 0 donors, respectively, and 3 non-typeable donors, and verified that gp-340 glycoforms I and II/III correlate with Se(-) and Se(+) phenotypes, respectively (p < 0.0001). The glycoforms of saliva and lung gp-340 mediated differential aggregation of Le(b)-(Helicobacter pylori), sialylpolylactosamine(Streptococcus suis) or sialic acid- (Streptococcus mutans) binding bacteria. In conclusion, variant size- and glycoforms of gp-340 are expressed by different individuals and may modulate the biological properties of gp-340 pertinent to health and disease.
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| 4. |
- Kouki, Annika, et al.
(author)
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Bacterial adhesion of Streptococcus suis to host cells and its inhibition by carbohydrate ligands
- 2013
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In: Biology. - : MDPI AG. - 2079-7737. ; 2:3, s. 918-935
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Research review (peer-reviewed)abstract
- Streptococcus suis is a Gram-positive bacterium, which causes sepsis and meningitis in pigs and humans. This review examines the role of known S. suis virulence factors in adhesion and S. suis carbohydrate-based adhesion mechanisms, as well as the inhibition of S. suis adhesion by anti-adhesion compounds in in vitro assays. Carbohydrate-binding specificities of S. suis have been identified, and these studies have shown that many strains recognize Galα1-4Gal-containing oligosaccharides present in host glycolipids. In the era of increasing antibiotic resistance, new means to treat infections are needed. Since microbial adhesion to carbohydrates is important to establish disease, compounds blocking adhesion could be an alternative to antibiotics. The use of oligosaccharides as drugs is generally hampered by their relatively low affinity (micromolar to compete with multivalent binding to host receptors. However, screening of a library of chemically modified Galα1-4Gal derivatives has identified compounds that inhibit S. suis adhesion in nanomolar range. Also, design of multivalent Galα1-4Gal-containing dendrimers has resulted in a significant increase of the inhibitory potency of the disaccharide. The S. suis adhesin binding to Galα1-4Gal-oligosaccharides, Streptococcal adhesin P (SadP, was recently identified. It has a Galα1-4Gal-binding N-terminal domain and a C-terminal LPNTG-motif for cell wall anchoring. The carbohydrate-binding domain has no homology to E. coli P fimbrial adhesin, which suggests that these Gram-positive and Gram-negative bacterial adhesins recognizing the same receptor have evolved by convergent evolution. SadP adhesin may represent a promising target for the design of anti-adhesion ligands for the prevention and treatment of S. suis infections.
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| 5. |
- Kouki, Annika, et al.
(author)
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Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-alpha 1-4-galactose-containing Glycoconjugates CONVERGENT EVOLUTION OF BACTERIAL PATHOGENS TO BINDING OF THE SAME HOST RECEPTOR
- 2011
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In: Journal of Biological Chemistry. - 1083-351X. ; 286:45, s. 38854-38864
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Journal article (peer-reviewed)abstract
- Bacterial adhesion is often a prerequisite for infection, and host cell surface carbohydrates play a major role as adhesion receptors. Streptococci are a leading cause of infectious diseases. However, only few carbohydrate-specific streptococcal adhesins are known. Streptococcus suis is an important pig pathogen and a zoonotic agent causing meningitis in pigs and humans. In this study, we have identified an adhesin that mediates the binding of S. suis to galactosyl-alpha 1-4-galactose (Gal alpha 1-4Gal)-containing host receptors. A functionally unknown S. suis cell wall protein (SSU0253), designated here as SadP (streptococcal adhesin P), was identified using a Gal alpha 1-4Gal-containing affinity matrix and LC-ESI mass spectrometry. Although the function of the protein was not previously known, it was recently identified as an immunogenic cell wall protein in a proteomic study. Insertional inactivation of the sadP gene abolished S. suis Gal alpha 1-4Gal-dependent binding. The adhesin gene sadP was cloned and expressed in Escherichia coli. Characterization of its binding specificity showed that SadP recognizes Gal alpha 1-4Gal-oligosaccharides and binds its natural glycolipid receptor, GbO(3) (CD77). The N terminus of SadP was shown to contain a Gal alpha 1-Gal-binding site and not to have apparent sequence similarity to other bacterial adhesins, including the E. coli P fimbrial adhesins, or to E. coli verotoxin or Pseudomonas aeruginosa lectin I also recognizing the same Gal alpha 1-4Gal disaccharide. The SadP and E. coli P adhesins represent a unique example of convergent evolution toward binding to the same host receptor structure.
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| 6. |
- Loimaranta, Vuokko, et al.
(author)
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Leucine-rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor gp340.
- 2009
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 284:28, s. 18614-23
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Sheng, Nongfei, 1988-
(author)
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Revisiting dental caries as an immunodeficiency disorder
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Worldwide, dental caries is the major human chronic disease, with billions of people affected in terms of life quality impairment and high society costs that consumes 5-10% of the global healthcare budget. In Western countries dental caries has declined dramatically, with a trajectory of 15% high-risk individuals with recurrent caries and a non-responder behavior to standard prevention. This dissertation work focuses on revisiting the primary causes of caries development by exploring human and Streptococcus mutans genetic variation in a prospective case-control sample of 452 Swedish adolescents followed from 12 and 17 years of age.Genetic variation of PRH1 and PRH2, encoding acidic proline-rich protein receptors for indigenous oral streptococci and actinomycetes, specified high (P4a), moderate (P6) and low (P1) caries phenotypes of different risk and causal profiles (Paper I). Susceptible individuals thus classified into the immunodeficiency caries type (P4a) or the lifestyle caries type (P1) that accounted for naturally resistant individuals. Orthodontic treatment during adolescence exerted a further negative load that resulted in an even bigger difference in caries progression between P4a and P1 individuals. Importantly, immunodeficiency P4a individuals were identified as risk individuals at the clinic and therefore given extra fluoride.Adhesin gene variation in S. mutans specified SpaP A/B/C and Cnm/Cbm adhesion types that matched individual caries progression (Paper II). The saliva/DMBT1 binding avidity of high cariogenicity SpaP and Cnm but not of low cariogenicity SpaP A types correlated positively with the caries activity of the individual strain donor. SpaP-guided MLST typing also revealed SpaP A/B/C biotypes with high SpaP B and low SpaP A cariogenicity lineages that besides adhesion differed in acid production and acid tolerance properties. The SpaP A/B/C receptor-binding V-regions had markedly different structures. In paper III, we found unstable residency of a mixed and fluctuating SpaP A/B/C adhesion mode, a high cariogenicity SpaP B-1 subtype and Cnm adhesin expression and glycosylation to contribute to mono-microbial caries progression in naturally resistant low caries P1 phenotypes. By, contrast, moderate- and high-caries P6 and P4a phenotypes contributed to poly- and meta-microbial caries progression. In addition, the S. mutans adhesion types showed specificity (tropism) for individual hosts and plausible family distribution patterns.DMBT1 protein size isoforms I-III predicted caries progression but differently in the PRH1/PRH2 genetic background and influenced the infection profile of S. mutans adhesion and virulence types (Paper IV). Caries progression increased as DMBT1 isoform size decreased in the order of isoform I > II > III, suggesting that loss of the large isoform III glycotype may impair immunity. The finding that DMBT1 isoform variation did not add predictive power to the P4a+ but to P4a- phenotypes allowed a novel sick and health classification system.In conclusion, PRH1, PRH2 may represent a pattern recognition and immunity pathway for tooth homeostasis and formation of the indigenous flora on teeth. It can predict prospective caries risk and might be implemented in caries prevention based on genetic risk and cause at the clinical level. DMBT1 appears as an evolutionary different but intertwined immunity pathway for surveillance of infectious agents in general at teeth and mucosal surfaces. The S. mutans organism is heterogenous with biotypes and lineages that match individual caries development. Narrowing both S. mutans and PRH1, PRH2 phenotypes suggest a mono- (P1), poly- (P6) and even meta- (P4a) microbial characters of dental caries.
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