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Narrowed Streptococcus mutans adhesion and human receptor phenotypes that match mono-, poly- and metamicrobial characters of dental caries
Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.ORCID-id: 0000-0002-2391-5903
Faculty of Odontology, Malmö University, Malmö, Sweden.
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Odontologi
Identifikatorer
URN: urn:nbn:se:umu:diva-208346OAI: oai:DiVA.org:umu-208346DiVA, id: diva2:1758199
Tillgänglig från: 2023-05-22 Skapad: 2023-05-22 Senast uppdaterad: 2023-05-22
Ingår i avhandling
1. Revisiting dental caries as an immunodeficiency disorder
Öppna denna publikation i ny flik eller fönster >>Revisiting dental caries as an immunodeficiency disorder
2023 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Karies som en immunbristsjukdom?
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2023. s. 88
Serie
Umeå University odontological dissertations, ISSN 0345-7532 ; 150
Nyckelord
caries, immunodeficiency, proline-rich proteins, DMBT1, S. mutans, adhesin, SpaP, Cnm, Cbm, collagen binding, caries risk stratification, precision dentistry
Nationell ämneskategori
Odontologi
Identifikatorer
urn:nbn:se:umu:diva-208357 (URN)978-91-8070-106-8 (ISBN)978-91-8070-107-5 (ISBN)
Disputation
2023-06-13, Hörsal B, 9 tr, Byggnad 1D, Norrlands universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2023-05-25 Skapad: 2023-05-22 Senast uppdaterad: 2023-05-23Bibliografiskt granskad

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Sheng, NongfeiMårell, LenaSitaram, Raviprakash TumkurStrömberg, Nicklas

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