Fusobacterium nucleatum is a gram-negative anaerobe, which belongs to theBacteroidaceae family and is found naturally in the microflora of the mouth in healthy or diseased humans. F. nucleatum is a very long rod with tapering ends and is one of the dominant species of the 500 or more organisms that coexist in the oral cavity (21). Many of the oral flora are commensals but a few are opportunistic pathogens. F. nucleatum can be isolated not only from the mouth but also from infections such as skin ulcers, peritonsillar abscesses, septic arthritis, and endocarditis (5). Several species of Fusobacterium have been isolated and studied, including F. necrophorum(the causative agent of Lemierre’s syndrome), F. ulcercans (skin ulcers), F. russi(animal bite infections), and F. varium (eye infections), with F. nucleatum and F. necrophorum considered to be the most pathogenic.
In the initial stages of the periodontal disease process, saccharolytic, aerobic
Streptococcus spp. and other bacteria adhere to and colonize the tooth enamel and root surface. This sets the stage for
F. nucleatum to coaggregate with these early colonizers and to permit late colonizers, including dental pathogens, to eventually form a biofilm. These complex interactions result in the release of factors that lead to tooth decay. Physical interaction is very specific among various genera in this complex microbial community. Due to the unusual length, adhesive nature, and other cell surface properties of
F. nucleatum, periodontal disease-causing bacteria such as
Porphyromonas gingivalis,
Bacteroides forsythus,
Actinobacillus actinomycetemcomitans,
Treponema denticola, and
Streptococcus spp. aggregate and thrive; hence,
F. nucleatum is referred to as a “bridge bacterium” (
5). The interaction between
F. nucleatum and
P. gingivalis has been reported to be very specific (
19), mediated by a lactose-binding adhesin (
20). The same adhesin protein mediates the binding of
F. nucleatum to a variety of eukaryotic cell types including HeLa cells, buccal epithelial cells, macrophages, polymorphonuclear leukocytes, and gingival and periodontal ligaments (
46).
Helicobacter pylori was also shown to adhere selectively to
F. nucleatum (
1).
Research on
Fusobacterium spp. has focused primarily on species identification, oral ecology, cell-cell communication, extracellular surfaces, amino acid degradation, carbohydrate metabolism, organic acid fermentation, and antibiotic resistance (
5,
21). However, many metabolic pathways and their roles in survival in such specialized niches are not known. Genetic experiments have been hampered by the lack of molecular tools, although recently three plasmids, pFN1, pFN2, and pFN3, have been isolated and sequenced from the strain ATCC 10953. A transformation system has been developed for gene manipulation using the pFN1
ori sequence (
14).
Although many potential virulence candidates have been described, very few of them have been studied experimentally. In an effort to understand globally its genetic, metabolic, and pathogenic features, we analyzed the genome sequence of F. nucleatum strain ATCC 25586 and present here the results of this analysis. This is the first determination of a Fusobacterium spp. genome sequel
drsushant