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[Lemierre syndrome variant: Hepatic abscesses and hepatic venous thrombosis due to Fusobacterium nucleatum septicemia].

INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemierre's syndrome. Various locations of venous thrombosis have been described associated with Fusobacterium sp. septicemia. EXEGESIS: We describe a 43-year old alcoholic patient with F.nucleatum septicemia complicated with hepatic abscesses, middle hepatic venous thrombosis, osteomyelitis and infiltrative pneumonia. A pancreatic prosthesis was the only potentially identified infectious entrance. CONCLUSION: Our patient showed an alternative presentation of Lemierre's syndrome, a "digestive variant". To the best of our knowledge, this is the first report of Fusobacterium septicemia associated with hepatic venous thrombosis. This report is close to the cases of portal thrombosis and opens the clinical sphere of the lemierre's syndrome, whose incidence is increasing.

Adult↗

Cytokine, elastase and oxygen radical release by Fusobacterium nucleatum-activated leukocytes: a possible pathogenic factor in periodontitis.

Periodontitis is characterised by tissue destruction caused by reactive oxygen species (ROS) and proteolytic enzymes, which are released by the interaction between bacteria and phagocytes. We estimated the ability of Fusobacterium species to induce release of tissue destructive and proinflammatory mediators from in vitro activated peripheral leukocytes. ROS was measured with the nitroblue tetrazolium (NBT) method, elastase with a specific chromogenic substrate and cytokines, including interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) with a sandwich ELISA method. Various clinical isolates of unopsonized Fusobacterium species stimulated the neutrophils to an increased NBT- reduction. IL-1beta, TNFalpha, IL-8 and elastase were released in significantly higher levels from neutrophils stimulated by Fusobacterium species. In conclusion, unopsonized Fusobacterium species can induce increased production of oxygen radicals, cytokines and elastase from leukocytes activated in vitro.

Analysis of Variance↗

Helicobacter pylori adheres selectively to Fusobacterium spp.

Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their ability to coaggregate with 79 strains of bacteria representing 16 genera. All except two of the strains were of human origin, and most of the strains were isolated from the oral cavity. The helicobacters failed to coaggregate with all strains except the fusobacteria. Several coaggregations were partially or completely inhibited by lactose. Strong coaggregation was seen with each of four subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC 33693, all of human dental plaque origin. In contrast, the helicobacters failed to coaggregate with non-plaque isolates, Fusobacterium mortiferum ATCC 25557 and Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated their ability to coaggregate, whereas heating of the Helicobacter partners had no effect, suggesting the presence of an adhesin on the fusobacteria and a corresponding receptor on the helicobacters. The potential ability of H. pylori to colonize the oral cavity by adhering selectively to the ubiquitous fusobacteria gives credence to the possibility that dental plaque may serve as a reservoir for this pathogen outside of the stomach.

Bacterial Adhesion↗

Evolutionary relationships of Fusobacterium nucleatum based on phylogenetic analysis and comparative genomics.

BACKGROUND: The phylogenetic position and evolutionary relationships of Fusobacteria remain uncertain. Especially intriguing is their relatedness to low G+C Gram positive bacteria (Firmicutes) by ribosomal molecular phylogenies, but their possession of a typical gram negative outer membrane. Taking advantage of the recent completion of the Fusobacterium nucleatum genome sequence we have examined the evolutionary relationships of Fusobacterium genes by phylogenetic analysis and comparative genomics tools. RESULTS: The data indicate that Fusobacterium has a core genome of a very different nature to other bacterial lineages, and branches out at the base of Firmicutes. However, depending on the method used, 35-56% of Fusobacterium genes appear to have a xenologous origin from bacteroidetes, proteobacteria, spirochaetes and the Firmicutes themselves. A high number of hypothetical ORFs with unusual codon usage and short lengths were found and hypothesized to be remnants of transferred genes that were discarded. Some proteins and operons are also hypothesized to be of mixed ancestry. A large portion of the Gram-negative cell wall-related genes seems to have been transferred from proteobacteria. CONCLUSIONS: Many instances of similarity to other inhabitants of the dental plaque that have been sequenced were found. This suggests that the close physical contact found in this environment might facilitate horizontal gene transfer, supporting the idea of niche-specific gene pools. We hypothesize that at a point in time, probably associated to the rise of mammals, a strong selective pressure might have existed for a cell with a Clostridia-like metabolic apparatus but with the adhesive and immune camouflage features of Proteobacteria.

Bacterial Proteins↗

Fusobacterium nucleatum involvement in adult periodontitis and possible modification of strain classification.

BACKGROUND: This investigation was designed to evaluate the involvement of Fusobacterium nucleatum clinical strains in adult periodontitis by subspecies and expression of hemagglutination activity. METHODS: Forty-nine Fusobacterium strains were isolated from 40 sites in 40 subjects presenting with adult periodontitis. F. nucleatum subspecies identification was based on the electrophoretic migration of glutamate dehydrogenase and 2-oxoglutarate reductase. Hemagglutination activity and inhibition by galactose were tested on sheep erythrocytes. RESULTS: The 49 isolates belonged to the F. nucleatum species with a predominance of the nucleatum (34.7%) followed by the vincentii (26.5%) subspecies. In parallel, 71% of the strains belonging to the nucleatum subspecies were preferentially associated with Porphyromonas gingivalis. Prevotella intermedia/nigrescens detection was essentially correlated with identification of Fusobacterium nucleatum subspecies vincentii. No correlation was established between any particular subspecies and the pathogenicity factors tested (hemagglutination and production of short-chain fatty acids). On the other hand, significant predominance (65%, P= 0.017) of strongly hemagglutinating strains (titre > or =8 U) was observed in the sites where Porphyromonas gingivalis, Prevotella intermedia/nigrescens and/or Campylobacter rectus were not detected. These strains also showed higher butyric acid production. CONCLUSION: The importance of the adherence factors for Fusobacterium nucleatum strains and their multimodal aspect may indicate a higher pathogenicity or a higher involvement of certain strains and could lead to a classification of these strains, which is more closely related to their implication in the development of periodontal disease.

Adult↗

Studies on bacterial synergism in mice infected with Bacteroides intermedius and Fusobacterium necrophorum.

This study was undertaken to characterize the kinetics of possible bacterial synergy using a mouse model of mixed intraabdominal infection with Bacteroides intermedius and Fusobacterium necrophorum. Female CD-1 mice were injected intraperitoneally with B. intermedius, F. necrophorum or mixtures of both organisms. Generalized septic peritonitis developed within 24 hr, with abscess formation occurring after one to two wk in survivors with the mixed infection. Involvement of the reticuloendothelial system was evidenced by dose-dependent hepatosplenomegaly, which appeared during the first wk postinfection and progressed throughout the course of the experiment. Indirect immunofluorescence confirmed the presence of both species of bacteria in frozen sections of liver tissue. The median lethal dose (LD50) was 2.11 x 10(9) for the mixture, 3.03 X 10(9) for B. intermedius alone, and 1.07 X 10(9) for F. necrophorum alone. The median abscess-producing dose (AD50), the dose required to produce abscesses in fifty percent of the surviving mice at two wk, was approx. 1/100 of the LD50 dose. The AD50 for intrahepatic abscesses was 2.8 x 10(8) for the mixture, whereas the AD50 for intraabdominal abscesses occurring in any site was 5.14 X 10(7). Both Bacteroides and Fusobacterium persisted in tissue for at least 22 wk following mixed infection. The persistence of the Bacteroides in tissue represents a synergistic result of mixed infection with Fusobacterium and contributed to the chronicity of intraabdominal abscess formation. Bacteroides, injected alone, did not produce abscesses at any of the doses tested. However, when passaged (isolated from mixed infection hepatic abscesses) B. intermedius was used, the bacteria did induce abscesses.

Abscess↗

Liver abscesses due to Fusobacterium spp that mimick malignant metastatic liver disease.

A 71-year-old man presented with the clinical and radiological features of metastatic liver disease but subsequently was found to have multiple liver abscesses caused by Fusobacterium necrophorum. At liver biopsy, pus was aspirated and Fusobacterium necrophorum was isolated from the pus. Serial blood cultures and urine cultures were sterile and negative for Fusobacterium spp. The patient made a complete recovery in response to treatment with penicillin and amoxicillin. This case illustrates the importance of liver abscesses as an uncommon but completely treatable differential diagnosis for the radiological appearances of multiple hepatic lesions.

Aged↗

Fusobacterium necrophorum as the cause of recurrent sore throat: comparison of isolates from persistent sore throat syndrome and Lemierre's disease.

OBJECTIVE: Fusobacterium necrophorum is a well established cause of Lemierre's disease (LD); a syndrome characterised by severe sore throat, septicaemia, multiple abscesses and jugular vein thrombosis. There is no published data concerning the role of F. necrophorum in recurrent sore throats. As the result of an index case of persistent sore throat attributable to this organism being diagnosed in our laboratory, a subsequent case controlled study (not yet published) isolated F. necrophorum from 21% (P=0.0001) of cases of persistent, recurrent and chronic sore throats. The object of this study was to compare isolates of F. necrophorum from cases of systemic disease with isolates from cases of persistent sore throat syndrome (PSTS) to ascertain whether strains of similar type were responsible for both throat and systemic disease or whether different strains were involved in these presentations. METHODS: Throat swabs were cultured on GN anaerobe medium (Oxoid) and incubated at 37 degrees C for 5 days. Seventeen PSTS isolates were identified phenotypically. These were compared to 17 strains isolated from blood cultures which were referred to the Anaerobe Reference Unit, (ARU) cardiff, using enterogenic repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). The control strains Fusobacterium necrophorum ssp. necrophorum (JCM 3718(T)) and Fusobacterium necrophorum ssp. funduliforme (JCM 3724(T)) from the Japanese Collection of Microrganisms (JCM) were tested in parallel with the clinical isolates. RESULTS: At least 12 separate types were identified. Four of 17 PSTS isolates and seven of 17 blood culture isolates grouped together with the F. necrophorum ssp. funduliforme control strain. There were also similarities between other proposed strains and clinical types but no comparison with the F. necrophorum ssp. necrophorum control. CONCLUSION: These results show that clinical disease caused by F. necrophorum has a wider spectrum than first anticipated. Similar strains are able to cause either chronic local or acute systemic disease suggesting that genetic factors such as those relating to major histocompatibility complex (MHC) class may be influencing the outcome of the disease in each patient. Further work is required to produce a more accurate typing scheme and to ascertain the mechanisms of disease caused by this organism. An age correlation between the high risk groups for onset of infectious mononucleosis (IM), peritonsillar abscess (PTA), LD and PSTS has been noted in adolescents and young adults. Further work is required to investigate whether IM is associated with the onset of PTA caused by F. necrophorum which may lead to either PSTS or LD.

Adolescent↗

Multiple brain abscesses caused by Fusobacterium nucleatum treated conservatively.

BACKGROUND: Multiple brain abscesses are serious neurological problems with high mortality and disabling morbidity. The frequency is rising as a result of AIDS and the increasing number of immunocompromised patients. CASE STUDY: A 59-year-old woman developed signs and symptoms of diffuse brain dysfunction including fever and neck stiffness. A brain CT scan demonstrated nine contrast-enhancing ring-shaped lesions. Analysis of the cerebrospinal fluid using PCR-technique revealed DNA of Fusobacterium nucleatum. Conservative treatment with antibiotics was successful. The patient recovered with only mild cognitive deficits. RESULTS: The experience of our patient and the review of the literature indicate that multiple brain abscesses due to Fusobacterium nucleatum are rare. The most probable source is oral infection. CONCLUSION: Multiple brain abscesses may be caused by Fusobacterium nucleatum. Cerebrospinal fluid analysis using PCR technique is helpful with diagnosis. Conservative management can be successful.

Anti-Bacterial Agents↗

Fusobacterium equinum sp. nov., from the oral cavity of horses.

Two strains of gram-negative, anaerobic, non-sporulating rod that were isolated from the normal oral cavity and oral-associated disease from horses and which phenotypically resembled Fusobacterium necrophorum were characterized by sequencing of the 16S rRNA gene, phylogenetic analysis, DNA-DNA hybridization and phenotypic characterization. The results placed the novel strains as distinct members of the genus Fusobacterium. The novel species Fusobacterium equinum sp. nov. is proposed, with strain VPB 4027T (= NCTC 13176T = JCM 11174T) as the type strain.

Animals↗

Fatty acids of Fusobacterium species: taxonomic implications.

Fatty acids of Fusobacterium species were examined by gas-liquid chromatography. Fusobacterium nucleatum, F. necrophorum, F. mortiferum, F. gonidiaformans and F. varium showed similar patterns, characterized by the presence of 3-hydroxytetradecanoate, n-tetradecanoate, hexadecenoate, n-hexadeconoate, ocadecenoate, n-octadecanoate and a component having the properties of octadecadienoate. Fusobacterium nucleatum contained 3-hydroxyhexadecanoate as a distinctive character. Simpler fatty acid patterns characterized by the absence of 3-hydroxytetradecanoate and other hydroxy fatty acids were observed in F. plauti, the single strain of F. prausnitzii and in the majority of strains classified as F. russii and F. naviforme. Neither methyl-branched nor cyclopropane fatty acids could be detected in any of the strains examined. In addition to fatty acid methyl esters, the chromatographic profiles of all species except F. mortiferum, F. gonidiaformans and F. naviforme contained substantial amounts of fatty aldehyde dimethyl acetals of chain lengths C14 to C18.

Chromatography, Gas↗

Fusobacterium nucleatum increases collagenase 3 production and migration of epithelial cells.

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.

Cell Movement↗

Characterization, distribution, and microbiological associations of Fusobacterium spp. in clinical specimens of animal origin.

During the years from 1984 through 1991, 1,067 specimens from canine, equine, exotic, feline, porcine, and ruminant animal sources were found to contain members of the genus Fusobacterium: The most common sites or conditions from which members of this genus were isolated were abscesses, the respiratory tract, and pleural and peritoneal cavities. Most specimens contained a single Fusobacterium species. The most commonly isolated species was Fusobacterium necrophorum. Almost all of the specimens contained other obligate anaerobes together with facultative and obligate aerobes. The identities of the other isolates depended upon the species of animal from which the sample was obtained.

Abscess↗

Meningitis due to Fusobacterium necrophorum in an adult.

BACKGROUND: Fusobacterium necrophorum may cause a number of clinical syndromes, collectively known as necrobacillosis. Meningitis is a significant cause of mortality, rarely reported in the adult population. CASE PRESENTATION: We report a fatal case of meningitis, caused by Fusobacterium necrophorum, secondary to otitis media in an alcoholic male. Diagnosis was delayed due to the typical slow growth of the organism. The clinical course was complicated by encephalitis and by hydrocephalus. The patient failed to respond to metronidazole and penicillin. The patient died on day 12 from increased intracranial pressure and brain stem infarction. CONCLUSIONS: This case emphasizes the need for a high index of clinical suspicion to make the diagnosis of Fusobacterium necrophorum meningitis. We recommend the use of appropriate anaerobic culture techniques and antimicrobial coverage for anaerobic organisms when the gram stain shows gram negative bacilli.

Brain↗

[Isolation and identification of oral spirochaetes and Fusobacterium in juvenile periodontitis].

Periodontal pocket specimens of 40 juveniles periodontitis (JP) and specimens from gingival sulcus in 40 normal juveniles (NP) were examined. 25 strains of anaerobic oral spirochaete (62.5%) (17 strains were Treponema microdentium, 3 strains macrodentium, 2 strains T orale, 3 strains Borrelia) and 21 strains of fusobacterium were isolated in 40 JP. In 40 NP, 2 strains of spirochaetes (5%) and 3 strains fusobacterium (7.5%) were found. This study shows that there is a relationship between the infection of spirochaeta, fusobacterium and JP.

Adolescent↗

[Pathogenicity of Fusobacterium. Apropos of 2 cases].

Two cases of severe septico-pyohaemia due to Fusobacterium necrophorum are reported. Clinical data from human cases and experimental results from infections of laboratory animal with Fusobacterium necrophorum suggest: the important role of individual factors which enhance anaerobic growth (i.e. decrease of tissular redox potential); the involvement of thrombophlebitis with septic thrombi increasing the frequency of metastases; the early and long-lasting bacterial localisation in tissues, particularly in the liver where the proliferation of Fusobacterium necrophorum in Küpffer cells impairs macrophage function.

Adult↗

Bacteriocin production by Fusobacterium isolates recovered from the oral cavity of human subjects with and without periodontal disease and of marmosets.

Bacteriocin production has been studied in very few anaerobic bacteria, and no report is available for Fusobacterium species. In the present study a total of 167 Fusobacterium isolates were tested for bacteriocin production: 70 isolates were obtained from the oral cavity of patients with periodontal disease, 47 were recovered from healthy oral sites of human subjects and 50 from the oral cavity of Callithrix penicillata. Autoantagonism and isoantagonism were observed when the bacteriocin-producing isolates were tested against themselves. Heteroantagonism was detected by testing the Fusobacterium isolates against 14 reference strains and 2 strains of Actinobacillus actinomycetemcomitans from our laboratory collection. The auto-, iso- and heteroantagonism phenomena observed in this comparative study suggest a possible ecological role for this (these) antagonistic substance(s) in the oral environment.

Animals↗