Fusobacterium nucleatum Increases Collagenase 3 Production and Migration of Epithelial Cells

Abstract

Fusobacterium nucleatum is closely associated with human periodontal diseases and may also be a causative agent in other infections, such as pericarditis, septic arthritis, and abscesses of tonsils and liver. Initiation and outcome of infective diseases depend critically on the host cell signaling system altered by the microbe. Production of proteinases by infected cells is an important factor in pericellular tissue destruction and cell migration. We studied binding of F. nucleatum to human epithelial cells (HaCaT keratinocyte line) and subsequent cell signaling related to collagenase 3 expression, cell motility, and cell survival, using a scratch wound cell culture model. F. nucleatum increased levels of 12 protein kinases involved in cell migration, proliferation, and cell survival signaling, as assessed by the Kinetworks immunoblotting system. Epithelial cells of the artificial wound margins were clearly preferential targets of F. nucleatum. The bacterium colocalized with lysosomal structures and stimulated migration of these cells. Of the 13 anaerobic oral bacterial species, F. nucleatum and Fusobacterium necrophorum were among the best inducers of collagenase 3 mRNA levels, a powerful matrix metalloproteinase. Production of collagenase 3 was detected in fusobacterium-infected cells and cell culture medium by immunocytochemistry, immunoblotting, and zymography. The proteinase production involved activation of p38 mitogen-activated protein kinase in the infected cells. The study suggests that F. nucleatum may be involved in the pathogenesis of periodontal diseases (and other infections) by activating multiple cell signaling systems that lead to stimulation of collagenase 3 expression and increased migration and survival of the infected epithelial cells.

Genomic analysis identifies association of Fusobacterium with colorectal carcinoma

“…nucleatum and other Fusobacterium species can elicit host proinflammatory response and possess virulence characteristics that promote their adhesiveness to host epithelial cells (Bachrach et al 2005;Uitto et al 2005) and their ability to invade into epithelial cells (Han et al 2000;Strauss et al 2011). Therefore, our findings of a tumoral enrichment of Fusobacterium spp.…”

Diverse Toll-Like Receptors Mediate Cytokine Production by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in Macrophages

“…Ghosh et al showed that all MAPK (p38, ERK, and JNK) inhibitors showed little or no effect on F. nucleatum cell wall-induced CCL20 secretion in human oral epithelial cells (26). F. nucleatum induces collagenase 3 gene expression in human keratinocytes (HaCaT cells) via a p38-but not ERK-dependent pathway (27). In addition, p38 and JNK, but not NF-B, mediate the induction of human ␤-defensin 2 (hBD-2) production in response to F. nucleatum in gingival epithelial cells (28).…”

Fusobacterium nucleatumin Periodontal Health and Disease

“…Of the 13 anaerobic oral bacterial species, F. nucleatum and necrophorum were among the best inducers of collagenase 3 mRNA levels, a powerful matrix metalloproteinase. This suggests that F. nucleatum may be involved in the pathogenesis of periodontal diseases by activating multiple cell signaling systems that lead to stimulation of collagenase 3 expression and increased migration and survival of the infected epithelial cells (Uitto et al, 2005). A crucial part of the epithelial defense system is the efficient recruitment of professional defense cells, especially of neutrophils, to the infection site.…”