Identification and Characterization of a Novel Adhesin Unique to Oral Fusobacteria

Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4905, USA.
Journal of Bacteriology (Impact Factor: 2.81). 09/2005; 187(15):5330-40. DOI: 10.1128/JB.187.15.5330-5340.2005
Source: PubMed


Fusobacterium nucleatum is a gram-negative anaerobe that is prevalent in periodontal disease and infections of different parts of the body. The organism has remarkable adherence properties, binding to partners ranging from eukaryotic and prokaryotic cells to extracellular macromolecules. Understanding its adherence is important for understanding the pathogenesis of F. nucleatum. In this study, a novel adhesin, FadA (Fusobacterium adhesin A), was demonstrated to bind to the surface proteins of the oral mucosal KB cells. FadA is composed of 129 amino acid (aa) residues, including an 18-aa signal peptide, with calculated molecular masses of 13.6 kDa for the intact form and 12.6 kDa for the secreted form. It is highly conserved among F. nucleatum, Fusobacterium periodonticum, and Fusobacterium simiae, the three most closely related oral species, but is absent in the nonoral species, including Fusobacterium gonidiaformans, Fusobacterium mortiferum, Fusobacterium naviforme, Fusobacterium russii, and Fusobacterium ulcerans. In addition to FadA, F. nucleatum ATCC 25586 and ATCC 49256 also encode two paralogues, FN1529 and FNV2159, each sharing 31% identity with FadA. A double-crossover fadA deletion mutant, F. nucleatum 12230-US1, was constructed by utilizing a novel sonoporation procedure. The mutant had a slightly slower growth rate, yet its binding to KB and Chinese hamster ovarian cells was reduced by 70 to 80% compared to that of the wild type, indicating that FadA plays an important role in fusobacterial colonization in the host. Furthermore, due to its uniqueness to oral Fusobacterium species, fadA may be used as a marker to detect orally related fusobacteria. F. nucleatum isolated from other parts of the body may originate from the oral cavity.

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    • "Generally, Gram-negative bacterial cell attachment to the host eukaryotic cells is mediated by capsule, fimbrial proteins or outer membrane proteins (OMP) (Bavington and Page, 2005). Outer membrane proteins mediating attachment to epithelial cells have been characterized in another species of Fusobacterium; F. nucleatum, a human oral pathogen (Han et al., 2005). We have shown that OMP mediate attachment of F. necrophorum to bovine endothelial cells (Kumar et al., 2013a). "
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    ABSTRACT: Fusobacterium necrophorum, a Gram-negative anaerobe, is the primary etiologic agent of liver abscesses in cattle. There are two subspecies; subsp. necrophorum and subsp. funduliforme, which differ in morphological, biochemical, molecular characteristics, and virulence. The subsp. necrophorum, which is more virulent, occurs more frequently in liver abscesses than the subsp. funduliforme. Bacterial adhesion to the host cell surface is critical to the pathogenesis of several bacterial infections, and in F. necrophorum, outer membrane proteins (OMP) have been shown to mediate adhesion to bovine endothelial cells. The objective of this study was to identify potential adhesins that are involved in adhesion of F. necrophorum subsp. necrophorum to the host cells. An OMP of 42.4 kDa, which binds with high affinity to the bovine endothelial cells and is recognized by the sera from cattle with liver abscesses, was identified. N-terminal sequencing of the protein showed 96% homology to the FomA protein of F. nucleatum. The PCR analysis showed that this fomA gene was present in several strains of subsp. necrophorum, subsp. funduliforme of bovine and subsp. funduliforme of human origin. The purified native and recombinantly expressed protein when preincubated with the endothelial cells, prevented the attachment of subsp. necrophorum significantly. In addition, the polyclonal antibody produced against the protein prevented the binding of subsp. necrophorum to bovine endothelial cells.
    Veterinary Microbiology 12/2014; 176(1-2). DOI:10.1016/j.vetmic.2014.12.015 · 2.51 Impact Factor
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    • "Roles of Microbes in Colitis-Associated Cancer Bacteria-derived virulence factors have been implicated in the initiation and promotion of CRC. In addition to causing a proinflammatory microenvironment that induces CRC (Kostic et al., 2013), Fusobacterium nucleatum, a Gram-positive commensal bacterium, has the capacity to induce CRC via the expression of the virulence factor FadA. FadA is a surface adhesion molecule (Ikegami et al., 2009) that facilitates the attachment and invasion of the microbe into the colonic epithelial cells (Han et al., 2005; Xu et al., 2007). FadA interacts with membranelocalized E-cadherin, which is important for maintenance of the integrity of colonic epithelial cells. "
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    ABSTRACT: In recent years, our understanding of the mechanisms underlying colorectal carcinogenesis has vastly expanded. Underlying inflammation within the intestine, diet, and most recently, the gut microbiota, have been demonstrated to influence the development of colorectal cancer. However, since cancer is ultimately a genetic disease, these factors are thought to create genotoxic stress within the intestinal environment to promote genetic and epigenetic alterations leading to cancer. In this review, we will focus on how gut microbes intersect with inflammation, diet, and host genetics to influence the development of colon cancer.
    Molecular cell 04/2014; 54(2):309-320. DOI:10.1016/j.molcel.2014.03.039 · 14.02 Impact Factor
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    • "For example, in vitro studies showed that S. gordonii provides H 2 O 2 to enhance the expression of ApiA in Aa (Ramsey and Whiteley, 2009). F. nucleatum possesses FadA, which can mediate its interaction with host epithelial cells (Han et al., 2005) and facilitates the penetration of non-invasive bacteria into endothelial cell layers in vitro (Fardini et al., 2011), suggesting that intra-bacterial interactions are potentially important for immunostimulation by non-invasive oral bacteria. "
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    ABSTRACT: An emerging concept is the tight relationship between dysbiosis (microbiota imbalance) and disease. The increase in knowledge about alterations in microbial communities that reside within the host has made a strong impact not only on dental science, but also on immunology and microbiology as well as on our understanding of several diseases. Periodontitis is a well-characterized human disease associated with dysbiosis, characterized by the accumulation of multiple bacteria that play individual and critical roles in bone loss around the teeth. Dysbiosis is largely dependent on cooperative and competitive interactions among oral microbes during the formation of the pathogenic biofilm community at gingival sites. Oral pathobionts play different and synergistic roles in periodontitis development, depending on their host-damaging and immunostimulatory activities. Host immune responses to oral pathobionts act as a double-edged sword not only by protecting the host against pathobionts, but also by promoting alveolar bone loss. Recent studies have begun to elucidate the roles of individual oral bacteria, including a new type of pathobionts that possess strong immunostimulatory activity, which is critical for alveolar bone loss. Better understanding of the roles of oral pathobionts is expected to lead to a better understanding of periodontitis disease and to the development of novel preventive and therapeutic approaches for the disease.
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