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Chapter 15 : Fusobacterium nucleatum Interaction with Host Cells
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Fusobacterium nucleatum is a gram-negative filamentous anaerobe ubiquitous to the oral cavity. While the focus of this chapter is on F. nucleatum interaction with host cells, the chapter also explains the role of coaggregation in oral microbial community interaction with the host. F. nucleatum is an opportunistic pathogen implicated in various forms of periodontal disease. During periodontal infection, the cell mass of F. nucleatum can increase as much as 10,000-fold, making it one of the most abundant anaerobic species in the diseased sites. In particular, F. nucleatum is one of the leading organisms identified in intrauterine infections causing adverse pregnancy outcomes, including spontaneous miscarriage, preterm birth, and stillbirth. One common feature shared by bacterial pathogens is their ability to adhere to and invade host cells. F. nucleatum modulates an array of host responses upon attachment to and invasion of host cells. A protein complex, FIP, composed of two subunits of 44 and 48 kDa, mediates T-cell suppression. Sequence analysis of TM7a shows that while the majority of the genes are only distantly related to genes found in other organisms, a minority share high sequence similarity with genes found in members of the classes Bacilli, Clostridia, and Fusobacteria, which may result from horizontal gene transfer in the oral cavity. FadA is a unique adhesin in that both the secreted mFadA and the intact pre-FadA are required for function.
Kinetic study of intravenous injection of F. nucleatum into pregnant mice. Mice were infected with a dose of 1 × 107 to 2.5 × 107 CFU of F. nucleatum 12230. At each time point, i.e., 6, 18, 24, 48, and 72 h postinfection, three or four mice were dissected. The bacterial counts in the placentas, liver, spleen, fetuses, and amniotic fluid (A.F.) of each mouse are expressed as log10 CFU per gram of tissue or per milliliter of fluid. The results shown are the averages for all mice dissected at each time point. The standard deviations were <20% for values of >1 log10 CFU/g but >50% for those of <1 log10 CFU/g. Reproduced from Infection and Immunity ( 29 ) with permission.
Transmission electron microscopy image of murine placenta at 24 h after infection with F. nucleatum 12230. R, red blood cells in the blood vessel. The solid arrows point to bacteria attached to or internalized in the endothelial cells lining the veins. The open arrows point to the bacteria in the blood vessel. Magnification, ×6,000. Reproduced from Infection and Immunity ( 29 ) with permission.
Amino acid sequence of FadA in one-letter code. The underlined residues encode the signal peptide, followed by mFadA. The central hairpin residues TRFY are marked by dotted lines, the leucine residues are marked by asterisks, and the histidine tag at the C terminus is italicized. Reproduced from J. Biol. Chem. ( 61 ) with permission.
Amino acid sequence alignment of FadA and its paralogues. Highlighted in gray are the identical residues shared among FadA. The sequences of three FadA paralogues, FNN1529 from F. nucleatum ATCC 25586, FNV2159 from F. nucleatum ATCC 49256, and FNP1049 from F. nucleatum ATCC 10953, are listed below the FadA sequence. The conserved and identical residues among FadA and the paralogues are indicated. Fn, F. nucleatum; Fp, F. periodonticum; Fs, F. simiae. The numbers above the sequence indicate amino acid positions in the secreted form of FadA, and the numbers beside the sequence indicate positions in the intact form. Reproduced from Journal of Bacteriology ( 28 ) with permission.
Colonization of F. nucleatum 12230, US1, and USF81 in the mouse placenta. Approximately 2 × 107 CFU of different F. nucleatum strains were injected into each pregnant CF-1 mouse via tail vein on day 16 of gestation. The placentas were harvested 6 h (open bars) or 24 h (solid bars) later. Live bacterial titers in the placentas were determined and are expressed as log10 CFU/g of tissue. The results shown are the averages for three to seven mice per strain. The standard deviations are expressed as lines above the bars. *, P < 0.05 compared to F. nucleatum 12230. Reproduced from Infection and Immunity ( 36 ) with permission.
Homology between FadA and proteins from different organisms