Autoinducer 2 of Fusobacterium nucleatum as a target molecule to inhibit biofilm formation of periodontopathogens.
Periodontitis is initiated by bacteria in subgingival biofilms, which are composed mostly of Gram-negative anaerobes. Autoinducer 2 (AI-2) is a universal quorum sensing (QS) molecule that mediates intergeneric signalling in multispecies bacterial communities and may induce biofilm formation. As Fusobacterium nucleatum is the major coaggregation bridge organism that links early colonising commensals and late pathogenic colonisers in dental biofilms via the accretion of periodontopathogens, we hypothesised that AI-2 of F. nucleatum contributes to this interspecies interaction, and interruption of this signalling could result in the inhibition of biofilm formation of periodontopathogens. To test this hypothesis, we evaluated the effect of partially purified F. nucleatum AI-2 on monospecies biofilm as well as mutualistic interactions between F. nucleatum and the so-called 'red complex' (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia). Then we tested the effect of two QS inhibitors (QSIs), (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (furanone compound) and d-ribose, on AI-2-induced biofilm formation and coaggregation. F. nucleatum AI-2 remarkably induced biofilm growth of single and dual species and coaggregation between F. nucleatum and each species of the 'red complex', all of which were inhibited by the QSIs. F. nucleatum AI-2 induced the expression of the representative adhesion molecules of the periodontopathogens, which were inhibited by the QSIs. Our results demonstrate that F. nucleatum AI-2 plays an important role in inter- and intraspecies interactions between periodontopathogens via enhanced expression of adhesion molecules and may be a target for the inhibition of pathogenic dental biofilm formation.
Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Yun-Ji
YJ
Jang
Yu-Jung
YJ
Choi
Sung-Hoon
SH
Lee
Hye-Kyoung
HK
Jun
Bong-Kyu
BK
Choi
D001422:Bacterial Adhesion / Q000187:drug effects; D018407:Bacterial Physiological Phenomena / Q000187:drug effects; D001431:Bacteriological Techniques; D001439:Bacteroides / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D018533:Biomass; D002460:Cell Line; D004396:Coloring Agents; D003470:Culture Media; D005347:Fibroblasts / Q000187:drug effects; D005663:Furans / Q000494:pharmacology / Q000633:toxicity; D016967:Fusobacterium nucleatum / Q000378:metabolism*; D005840:Gentian Violet; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006714:Homoserine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D007783:Lactones / Q000037:antagonists & inhibitors*; D049449:Luminescence; D050296:Microbial Viability / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D016966:Porphyromonas gingivalis / Q000187:drug effects; D053038:Quorum Sensing / Q000187:drug effects*; D012266:Ribose / Q000494:pharmacology / Q000633:toxicity; D048373:Treponema denticola / Q000187:drug effects
C454202:4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone; D004396:Coloring Agents; D003470:Culture Media; D005663:Furans; D018836:Inflammation Mediators; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D012266:Ribose; D006714:Homoserine; D005840:Gentian Violet