Filifactor alocis: Recent Insights and Advances

Filifactor alocis, a fastidious Gram-positive obligate anaerobic bacterium, is a newly appreciated member of the periodontal community that is now proposed to be a diagnostic indicator of periodontal disease. Its pathogenic characteristics are highlighted by its ability to survive in the oxidative stress–rich environment of the periodontal pocket and to significantly alter the microbial community dynamics by forming biofilms and interacting with several oral bacteria. Here, we describe the current understanding of F. alocis virulence attributes, such as its comparative resistance to oxidative stress, production of unique proteases and collagenases that can cause structural damage to host cells, and dysregulation of the immune system, which enable this bacterium to colonize, survive, and outcompete other traditional pathogens in the inflammatory environment of the periodontal pocket. Furthermore, we explore the recent advancements and future directions for F. alocis research, including the potential mechanisms for oxidative stress resistance and our evolving understanding of the interactions and mechanisms of bacterial survival inside neutrophils. We also discuss the current genetic tools and challenges involved in manipulating the F. alocis genome for the functional characterization of the putative virulence genes. Collectively, this information will expedite F. alocis research and should lead to the identification of prime targets for the development of novel therapeutics to aid in the control and prevention of periodontal disease.

Download Full-text

Porphyromonas gingivalis Ferrous Iron Transporter FeoB1 Influences Sensitivity to Oxidative Stress

Infection and Immunity ◽

10.1128/iai.00108-09 ◽

2009 ◽

Vol 78 (2) ◽

pp. 688-696 ◽

Cited By ~ 10

Author(s):

Cecilia Anaya-Bergman ◽

Jia He ◽

Kevin Jones ◽

Hiroshi Miyazaki ◽

Andrew Yeudall ◽

...

Keyword(s):

Oxidative Stress ◽

Mutant Strain ◽

Porphyromonas Gingivalis ◽

Ferrous Iron ◽

Atmospheric Oxygen ◽

Host Cells ◽

Periodontal Pathogen ◽

Bacterial Survival ◽

Deficient Mutant ◽

Iron Transporter

ABSTRACT Porphyromonas gingivalis FeoB1 is a ferrous iron transporter. Analysis of parental and feoB1-deficient strains of the periodontal pathogen revealed that the feoB1-deficient mutant strain had an increased ability to survive oxidative stress. Specifically, survival of the mutant strain was increased 33% with exposure to peroxide and 5% with exposure to atmospheric oxygen compared to the parental strain. Interestingly, the ability to survive intracellularly also increased fivefold in the case of the feoB1-deficient mutant. Our data suggest that although the FeoB1 protein is required for ferrous iron acquisition in P. gingivalis, it also has an adverse effect on survival of the bacterium under oxidative stress conditions. Finally, we show that feoB1 expression is not iron dependent and is dramatically reduced in the presence of host cells, consistent with the observed deleterious role it plays in bacterial survival.

Download Full-text

The bacterial association with oral cavity and intra-abdominal abscess after gastrectomy

PLoS ONE ◽

10.1371/journal.pone.0242091 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242091

Author(s):

Mao Nishikawa ◽

Michitaka Honda ◽

Ryosuke Kimura ◽

Ayaka Kobayashi ◽

Yuji Yamaguchi ◽

...

Keyword(s):

Periodontal Disease ◽

Oral Bacteria ◽

Periodontal Pocket ◽

Resected Stomach ◽

Bacterial Strains ◽

Drainage Fluid ◽

Stomach Mucosa ◽

Abdominal Infection ◽

Severe Periodontal Disease ◽

Intra Abdominal Infection

Background Perioperative oral management has been reported to be effective for preventing postoperative infectious complications. In addition, severe periodontal disease was identified as the significant risk factor for complications after gastrointestinal surgery. We investigated the bacteriological association between the periodontal pocket, stomach mucosa and drainage fluid to determine whether oral bacteria directly cause intra-abdominal infection after gastrectomy. Methods Patients who were scheduled to undergo surgery for gastric cancer were prospectively enrolled. We evaluated the similarity of bacterial strains in periodontal pocket, stomach mucosa and fluid from drainage tube. Gingival crevicular fluid and dental plaque were collected from the periodontal pocket and cultured to detect bacteria. Specimens from the resected stomach were collected and used for bacterial culturing. Drainage fluid from the abdominal cavity was also cultured. Results All of 52 patients were enrolled. In the periodontal pocket, α-Streptococcus spp., Neisseria sp., and Prevotella sp. were mainly detected. Bacterial cultures in the stomach mucosa were positive in 26 cases. In 20 cases (76.9%), the detected strains were the same as those in the periodontal pocket. Six patients had the postoperative intra-abdominal infection after gastrectomy, and the same bacterial strains was detected in both of drainage fluid and periodontal pocket in two patients with severe periodontal disease. Conclusions We found the bacteriological association that same strain detected in periodontal pocket, stomach and in intra-abdominal drainage fluid after gastrectomy in patients with periodontal disease.

Download Full-text

Aggregatibacter actinomycetemcomitans and Atherosclerosis

Journal of Integrative Cardiology Open Access ◽

10.31487/j.jicoa.2020.06.06 ◽

2020 ◽

pp. 1-6

Author(s):

Yutang Wang ◽

Dinh Tam Nguyen ◽

Jack Anesi ◽

Michelle Steicke ◽

Yutang Wang

Keyword(s):

Periodontal Disease ◽

Atherosclerotic Lesion ◽

Cell Types ◽

Aggregatibacter Actinomycetemcomitans ◽

Lesion Size ◽

Oral Bacteria ◽

Periodontal Pocket ◽

Inflammatory Condition ◽

Worldwide Population ◽

Bacterial Plaque

Periodontal disease is an inflammatory condition around the teeth which affects 20-50% of the worldwide population. In periodontal disease, the bacterial plaque destroys the epithelium of the periodontal pocket and breaks the barrier that separates the tissue and the circulation, allowing oral bacteria and their endotoxins and exotoxins to enter the bloodstream. This can cause health problems, such as atherosclerosis. Aggregatibacter actinomycetemcomitans (Aa) is commonly found in patients with periodontitis and the number of Aa is associated with atherosclerotic lesion size in humans. This review focuses on Aa and atherosclerosis with an emphasis on the interaction of Aa with cell types involved in atherosclerosis formation.

Download Full-text

Role of the Filifactor alocis Hypothetical Protein FA519 in Oxidative Stress Resistance

Microbiology Spectrum ◽

10.1128/spectrum.01212-21 ◽

2021 ◽

Author(s):

Ezinne Aja ◽

Arunima Mishra ◽

Yuetan Dou ◽

Hansel M. Fletcher

Keyword(s):

Oxidative Stress ◽

Periodontal Disease ◽

Stress Resistance ◽

Hypothetical Protein ◽

Content Type ◽

Genetic Tools ◽

Oxidative Stress Resistance ◽

Filifactor Alocis ◽

Diagnostic Indicator

Filifactor alocis is an emerging member of the periodontal community and is now proposed to be a diagnostic indicator of periodontal disease. However, due to the lack of genetic tools available to study this organism, not much is known about its virulence attributes.

Download Full-text

Oxidative Stress Parameters in Saliva and Its Association with Periodontal Disease and Types of Bacteria

Disease Markers ◽

10.1155/2015/653537 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 32

Author(s):

Jose Manuel Almerich-Silla ◽

Jose María Montiel-Company ◽

Sara Pastor ◽

Felipe Serrano ◽

Miriam Puig-Silla ◽

...

Keyword(s):

Oxidative Stress ◽

Periodontal Disease ◽

Periodontal Pocket ◽

Oxidative Stress Biomarkers ◽

Oxidative Stress Parameter ◽

Oxidative Stress Parameters ◽

Stress Parameter ◽

Periodontal Bacteria ◽

Different Types ◽

Stress Parameters

Objective. To determine the association between oxidative stress parameters with periodontal disease, bleeding, and the presence of different periodontal bacteria.Methods. A cross-sectional study in a sample of eighty-six patients, divided into three groups depending on their periodontal status. Thirty-three with chronic periodontitis, sixteen with gingivitis, and thirty-seven with periodontal healthy as control. Oxidative stress biomarkers (8-OHdG and MDA), total antioxidant capacity (TAOC), and the activity of two antioxidant enzymes (GPx and SOD) were determined in saliva. Subgingival plaque samples were obtained from the deepest periodontal pocket and PCR was used to determine the presence of the 6 fimA genotypes ofPorphyromonas gingivalis,Aggregatibacter actinomycetemcomitans,Tannerella forsythia, andTreponema denticola.Results. Periodontal disease was found to be associated with increased oxidative stress parameter levels. These levels rose according to the number and type of different periodontal bacteria found in the periodontal pockets. The presence of different types of periodontal bacteria is predictive independent variables in linear regresion models of oxidative stress parameters as dependent variable, above all 8-OHdG.Conclusions. Oxidative stress parameter levels are correlated with the presence of different types of bacteria. Determination of these levels and periodontal bacteria could be a potent tool for controlling periodontal disease development.

Download Full-text

Porphyromonas gingivalis-Epithelial Cell Interactions in Periodontitis

Journal of Dental Research ◽

10.1177/154405910608500502 ◽

2006 ◽

Vol 85 (5) ◽

pp. 392-403 ◽

Cited By ~ 97

Author(s):

E. Andrian ◽

D. Grenier ◽

M. Rouabhia

Keyword(s):

Epithelial Cells ◽

Periodontal Disease ◽

Porphyromonas Gingivalis ◽

Pathogenic Bacteria ◽

Current Knowledge ◽

Oral Bacteria ◽

Host Cells ◽

Host Responses ◽

Tissue Destruction ◽

Adaptive Ability

Emerging data on the consequences of the interactions between invasive oral bacteria and host cells have provided new insights into the pathogenesis of periodontal disease. Indeed, modulation of the mucosal epithelial barrier by pathogenic bacteria appears to be a critical step in the initiation and progression of periodontal disease. Periodontopathogens such as Porphyromonas gingivalis have developed different strategies to perturb the structural and functional integrity of the gingival epithelium. P. gingivalis adheres to, invades, and replicates within human epithelial cells. Adhesion of P. gingivalis to host cells is multimodal and involves the interaction of bacterial cell-surface adhesins with receptors expressed on the surfaces of epithelial cells. Internalization of P. gingivalis within host cells is rapid and requires both bacterial contact-dependent components and host-induced signaling pathways. P. gingivalis also subverts host responses to bacterial challenges by inactivating immune cells and molecules and by activating host processes leading to tissue destruction. The adaptive ability of these pathogens that allows them to survive within host cells and degrade periodontal tissue constituents may contribute to the initiation and progression of periodontitis. In this paper, we review current knowledge on the molecular cross-talk between P. gingivalis and gingival epithelial cells in the development of periodontitis.

Download Full-text

Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

Infection and Immunity ◽

10.1128/iai.01727-14 ◽

2014 ◽

Vol 82 (8) ◽

pp. 3261-3274 ◽

Cited By ~ 19

Author(s):

A. Wilson Aruni ◽

Kangling Zhang ◽

Yuetan Dou ◽

Hansel Fletcher

Keyword(s):

Epithelial Cells ◽

Porphyromonas Gingivalis ◽

Epigenetic Modification ◽

Polymicrobial Infection ◽

Host Cells ◽

Periodontal Pocket ◽

Membrane Microdomains ◽

Content Type ◽

Regulatory Pathways ◽

Filifactor Alocis

ABSTRACTChanges in periodontal status are associated with shifts in the composition of the bacterial community in the periodontal pocket. The relative abundances of several newly recognized microbial species, includingFilifactor alocis, as-yet-unculturable organisms, and other fastidious organisms have raised questions on their impact on disease development. We have previously reported that the virulence attributes ofF. alocisare enhanced in coculture withPorphyromonas gingivalis. We have evaluated the proteome of host cells andF. alocisduring a polymicrobial infection. Coinfection of epithelial cells withF. alocisandP. gingivalisstrains showed approximately 20% to 30% more proteins than a monoinfection. UnlikeF. alocisATCC 35896, the D-62D strain expressed more proteins during coculture withP. gingivalisW83 than withP. gingivalis33277. Proteins designated microbial surface component-recognizing adhesion matrix molecules (MSCRAMMs) and cell wall anchor proteins were highly upregulated during the polymicrobial infection. Ultrastructural analysis of the epithelial cells showed formation of membrane microdomains only during coinfection. The proteome profile of epithelial cells showed proteins related to cytoskeletal organization and gene expression and epigenetic modification to be in high abundance. Modulation of proteins involved in apoptotic and cell signaling pathways was noted during coinfection. The enhanced virulence potential ofF. alocismay be related to the differential expression levels of several putative virulence factors and their effects on specific host cell pathways.

Download Full-text

Proteomics of Extracellular Vesicles Produced by Granulicatella Species that cause Infective Endocarditis

10.1101/2019.12.27.889220 ◽

2019 ◽

Author(s):

Sarah A Alkandari ◽

Radhika G Bhardwaj ◽

Arjuna Ellepola ◽

Maribasappa Karched

Keyword(s):

Extracellular Vesicles ◽

Ribosomal Proteins ◽

Immune Modulation ◽

Bacterial Species ◽

Functional Characterization ◽

Oral Bacteria ◽

Human Pbmcs ◽

Bacterial Survival ◽

Dental Procedures ◽

Associated Proteins

AbstractWhen oral bacteria accidentally enter the bloodstream due to transient tissue damage during dental procedures, they have the potential to attach to the endocardium or an equivalent surface of an indwelling prosthesis and cause infection. Many bacterial species produce extracellular vesicles (EVs) as part of normal physiology, but also use it as a virulence strategy. In this study, it was hypothesized that Granulicatella species produce EVs that possibly help them in virulence. Therefore, the objectives were to isolate and characterize EVs produced by these species and to investigate their immune-stimulatory effects. The reference strains G. adiacens CCUG 27809 and G. elegans CCUG 38949 were cultured on chocolate blood agar for 2 days. From subsequent broth cultures, the EVs were isolated using differential centrifugation and filtration protocol and then observed using scanning electron microscopy. Proteins in the vesicle preparations were identified by nano LC-ESI-MS/MS. The EVs proteomes were analyzed and characterized using different bioinformatics tools. The immune-stimulatory effect of the EVs was studied via ELISA quantification of IL-8, IL-1β and CCL5, major proinflammatory cytokines, produced from stimulated human PBMCs. It was revealed that both G. adiacens and G. elegans produced EVs, ranging in diameter from 30 to 250 nm. Overall, G. adiacens EVs contained 160 proteins, and G. elegans EVs contained 107 proteins. Both proteomes consist of several ribosomal proteins, DNA associated proteins, binding proteins, and metabolic enzymes. It was also shown that these EVs carry putative virulence factors including moonlighting proteins. These EVs were able to induce the production of IL-8, IL-1β and CCL5 from human PBMCs. The diversity in EVs content indicates that these vesicles could have possible roles in bacterial survival, invasion, host immune modulation as well as infection. Further functional characterization of the Granulicatella EVs may provide new insights into virulence mechanisms of these important but less studied oral bacterial species.

Download Full-text

Filifactor alocis Has Virulence Attributes That Can Enhance Its Persistence under Oxidative Stress Conditions and Mediate Invasion of Epithelial Cells by Porphyromonas gingivalis

Infection and Immunity ◽

10.1128/iai.05631-11 ◽

2011 ◽

Vol 79 (10) ◽

pp. 3872-3886 ◽

Cited By ~ 61

Author(s):

A. Wilson Aruni ◽

Francis Roy ◽

H. M. Fletcher

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Porphyromonas Gingivalis ◽

Virulence Factors ◽

Clinical Isolates ◽

Periodontal Pocket ◽

Periodontal Pathogens ◽

Content Type ◽

Invasive Capacity ◽

Filifactor Alocis

ABSTRACTFilifactor alocis, a Gram-positive anaerobic rod, is one of the most abundant bacteria identified in the periodontal pockets of periodontitis patients. There is a gap in our understanding of its pathogenicity and ability to interact with other periodontal pathogens. To evaluate the virulence potential ofF. alocisand its ability to interact withPorphyromonas gingivalisW83, several clinical isolates ofF. alociswere characterized.F. alocisshowed nongingipain protease and sialidase activities.In silicoanalysis revealed the molecular relatedness of several virulence factors fromF. alocisandP. gingivalis. In contrast toP. gingivalis,F. alociswas relatively resistant to oxidative stress and its growth was stimulated under those conditions. Biofilm formation was significantly increased in coculture. There was an increase in adherence and invasion of epithelial cells in coculture compared withP. gingivalisorF. alocismonocultures. In those epithelial cells, endocytic vesicle-mediated internalization was observed only during coculture. TheF. alocisclinical isolate had an increased invasive capacity in coculture withP. gingivaliscompared to the ATCC 35896 strain. In addition, there was variation in the proteomes of the clinical isolates compared to the ATCC 35896 strain. Hypothetical proteins and those known to be important virulence factors in other bacteria were identified. These results indicate thatF. alocishas virulence properties that may enhance its ability to survive and persist in the periodontal pocket and may play an important role in infection-induced periodontal disease.

Download Full-text

Salivary Diagnosis - Clinical Uses in Assessing Oral Inflammation

Revista de Chimie ◽

10.37358/rc.17.6.5641 ◽

2017 ◽

Vol 68 (6) ◽

pp. 1201-1204 ◽

Cited By ~ 2

Author(s):

Iulia Ioana Stanescu ◽

Alexandra Totan ◽

Florentina Rus ◽

Daniela Miricescu ◽

Brandusa Mocanu ◽

...

Keyword(s):

Oxidative Stress ◽

Periodontal Disease ◽

Gingival Crevicular Fluid ◽

Oxidative Stress Marker ◽

Clinical Settings ◽

Tissue Destruction ◽

Whole Saliva ◽

Oral Inflammation ◽

Positive Correlations ◽

Crevicular Fluid

The past decades demonstrated that saliva and its components represent a remarkable diagnosis fluid with valuable clinical uses for both oral and systemic diseases. At the same time it is well established that oxidative stress is involved in a wide number of pathologies, including periodontitis. The specific aim of the present study which included 50 subjects is to determine if saliva can be used in clinical settings to correlate oxidative stress and tissue destruction markers with the severity of periodontal disease. An important oxidative stress marker - 8-hydroxydesoxyguanosine (8-OHdG) and a collagen degradation marker - beta-crosslaps (b-CTX) were quantified in both saliva and gingival crevicular fluid (GCF) using ELISA kits and were found to be significantly increased in the chronic periodontitis group when compared to respective controls (p[0.05). At the same time positive correlations were observed between whole saliva and gingival crevicular fluid (p[0.05). Significant correlations were also determined between GCF and salivary markers and clinical parameters of periodontal disease. Present results demonstrate that saliva and its components can successfully be used in clinical settings and represents a reliable tool for assessing periodontal disease severity.

Download Full-text