Sequence and Product Analyses of the Four Genes Downstream from the Fimbrilin Gene <i>(fimA)</i> of the Oral Anaerobe <i>Porphyromonas gingivalis</i>

Watanabe, Kôji; Onoe, Takaya; Ozeki, Masami; Shimizu, Yoshiyuki; Sakayori, Toshiko; Nakamura, Hiroshi; Yoshimura, Fuminobu

doi:10.1111/j.1348-0421.1996.tb01133.x

Cited by 41 publications

(42 citation statements)

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“…Copyright 2006 American Society for Microbiology. (A) The P. gingivalis 33277 fimbrial gene cluster contains fimA, encoding the main fimbrillin subunit, and fimCDE encoding accessory proteins associated with fimbriae (the role of ORF1 is unknown, although its product is not associated with fimbriae) (Watanabe et al, 1996;Nishiyama et al, 2007). The direction of transcription for each ORF is shown with the TIGR designation below the ORF.…”

Section: Resultsmentioning

confidence: 99%

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Hajishengallis

Wang²,

Liang³

et al. 2008

Advances in Experimental Medicine and Biology

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The capacity of certain pathogens to exploit innate immune receptors enables them to undermine immune clearance and persist in their host, often causing disease. Here we review subversive interactions of Porphyromonas gingivalis, a major periodontal pathogen, with the complement receptor-3 (CR3; CD11b/CD18) in monocytes/macrophages. Through its cell surface fimbriae, P. gingivalis stimulates Toll-like receptor-2 (TLR2) inside-out signaling which induces the highaffinity conformation of CR3. Although this activates CR3-dependent monocyte adhesion and transendothelial migration, P. gingivalis has co-opted this TLR2 proadhesive pathway for CR3 binding and intracellular entry. In CR3-deficient macrophages, the internalization of P. gingivalis is reduced 2-fold but its ability to survive intracellularly is reduced 1000-fold, indicating that CR3 is exploited by the pathogen as a relatively safe portal of entry. The interaction of P. gingivalis fimbriae with CR3 additionally inhibits production of bioactive (p70) interleukin-12, which mediates immune clearance. In vivo blockade of CR3 leads to reduced persistence of P. gingivalis in the mouse host and diminished ability to cause periodontal bone loss, the hallmark of periodontal disease. Strikingly, the ability of P. gingivalis to interact with and exploit CR3 depends upon quantitatively minor components (FimCDE) of its fimbrial structure, which predominantly consists of polymerized fimbrillin (FimA). Indeed, isogenic mutants lacking FimCDE but expressing FimA are dramatically less persistent and virulent than the wild-type organism both in vitro and in vivo. This model of immune evasion through CR3 exploitation by P. gingivalis supports the concept that pathogens evolved to manipulate innate immune function for promoting their adaptive fitness.

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Section: Resultsmentioning

confidence: 99%

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Hajishengallis

Wang²,

Liang³

et al. 2008

Advances in Experimental Medicine and Biology

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“…In addition, the molecular mechanism involved in the regulation of fimA expression is beginning to be understood. A two-component system (FimS-FimR) that regulates expression has been identified (Hayashi et al, 2000;Watanabe-Kato et al, 1998;Watanabe et al, 1996), and recently it was shown that the response regulator of this two-component system (FimR) controls the expression of these genes at the transcription level (Nishikawa et al, 2004). In regard to mfa1, expression of this gene has been shown to be affected by cell-to-cell contact with a variety of oral streptococci; either upregulation or downregulation was observed, depending on the species (Park et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

A streptococcal effector protein that inhibits Porphyromonas gingivalis biofilm development

Christopher¹,

Arndt

Cugini³

et al. 2010

Microbiology

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Dental plaque formation is a developmental process involving cooperation and competition within a diverse microbial community, approximately 70 % of which is composed of an array of streptococci during the early stages of supragingival plaque formation. In this study, 79 cell-free culture supernatants from a variety of oral streptococci were screened to identify extracellular compounds that inhibit biofilm formation by the oral anaerobe Porphyromonas gingivalis strain 381. The majority of the streptococcal supernatants (61 isolates) resulted in lysis of P. gingivalis cells, and some (17 isolates) had no effect on cell viability, growth or biofilm formation. One strain, however, produced a supernatant that abolished biofilm formation without affecting growth rate. Analysis of this activity led to the discovery that a 48 kDa protein was responsible for the inhibition. Protein sequence identification and enzyme activity assays identified the effector protein as an arginine deiminase. To identify the mechanism(s) by which this protein inhibits biofilm formation, we began by examining the expression levels of genes encoding fimbrial subunits; surface structures known to be involved in biofilm development. Quantitative RT-PCR analysis revealed that exposure of P. gingivalis cells to this protein for 1 h resulted in the downregulation of genes encoding proteins that are the major subunits of two distinct types of thin, single-stranded fimbriae (fimA and mfa1). Furthermore, this downregulation occurred in the absence of arginine deiminase enzymic activity. Hence, our data indicate that P. gingivalis can sense this extracellular protein, produced by an oral streptococcus (Streptococcus intermedius), and respond by downregulating expression of cell-surface appendages required for attachment and biofilm development. INTRODUCTIONHigh cell density and microbial diversity are fundamental to the development and function of the oral biofilm (Kolenbrander et al., 2002). The close proximity of cells within the biofilm facilitates cell-cell interactions, while the diversity offers a wide variety of metabolic functions, allowing the community to acquire nutrients and persist. During plaque formation, organisms affect the activities of one another via physical associations and through the release of extracellular molecules; the effects of these interactions range from mutualistic to antagonistic (Davey & Costerton, 2006;Socransky & Haffajee, 2000). Molecules that are excreted by bacteria into the environment or directly into host cells (through either non-classical or conventional secretion pathways), affecting gene expression of another organism, are often referred to as effectors. The primary objective of this study was to identify effectors produced by oral streptococci that modulate biofilm formation by the oral anaerobe Porphyromonas gingivalis. P. gingivalis is a Gram-negative anaerobe that persists within the oral biofilm community. Outgrowth of this normally commensal organism is associated with severe periodontal disease, r...

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“…Nishikawa et al (2004) identified fimX, a gene upstream of fimA, as a target of the FimS/FimR twocomponent regulatory system which controls the expression of fimA. Watanabe et al (1996) sequenced the region (~5 kb) downstream of fimA and identified four open reading frames (ORF1, ORF2, ORF3 and ORF4). The ORF2 and ORF3 products were reported to be minor components in fimbriae purified from strain 381 and inferred to play critical roles in fimbrial functions (Yoshimura et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Proteins were separated with a 12 % (w/v) SDS-PAGE gel and visualized by staining with Coomassie brilliant blue (CBB) R-250. For immunoblotting, proteins were transferred onto a nitrocellulose membrane (Hybond ECL nitrocellulose membrane, GE Healthcare Biosciences) and detected by using antibody raised against fimbrilin (FimA monomer) (Yoshimura et al, 1984), ORF1, FimC, FimD (Watanabe et al, 1996), or FimE (this study), and peroxidase-conjugated goat anti-rabbit IgG (MP Biomedicals). Signals were visualized with 0.01 % (w/v) 4-chloro-1-naphthol in 20 mM Tris/HCl (pH 7.5) containing 0.5 M NaCl supplemented with hydrogen peroxide.…”

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Involvement of minor components associated with the FimA fimbriae of Porphyromonas gingivalis in adhesive functions

et al. 2007

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The FimA fimbriae of Porphyromonas gingivalis, the causative agent of periodontitis, have been implicated in various aspects of pathogenicity, such as colonization, adhesion and aggregation. In this study, the four open reading frames (ORF1, ORF2, ORF3 and ORF4) downstream of the fimbrilin gene (fimA) in strain ATCC 33277 were examined. ORF2, ORF3 and ORF4 were demonstrated to encode minor components of the fimbriae and were therefore renamed fimC, fimD and fimE, respectively. Immunoblotting analyses revealed that inactivation of either fimC or fimD by an ermF-ermAM insertion, but not inactivation of ORF1, was accompanied by concomitant loss of the products from the downstream genes, raising the possibility that fimC, fimD and fimE constitute a transcription unit. The fimE mutant produced FimC and FimD, but fimbriae purified from it contained neither protein, suggesting that FimE is required for the assembly of FimC and FimD onto the fimbrilin (FimA) fibre. The fimC, fimD and fimE mutants lost autoaggregation abilities. Fimbriae purified from these three mutants showed attenuated binding activities to glyceraldehyde-3-phosphate dehydrogenase of Streptococcus oralis and to two extracellular matrix proteins, fibronectin and type I collagen. These results suggest that FimE, as well as FimC and FimD, play critical roles in the adhesive activities of the mature FimA fimbriae in P. gingivalis.

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Sequence and Product Analyses of the Four Genes Downstream from the Fimbrilin Gene (fimA) of the Oral Anaerobe Porphyromonas gingivalis

Cited by 41 publications

References 50 publications

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

A streptococcal effector protein that inhibits Porphyromonas gingivalis biofilm development

Involvement of minor components associated with the FimA fimbriae of Porphyromonas gingivalis in adhesive functions

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