Paediatric otogenic sinus venous thrombosis: the role of Fusobacterium necrophorum.

Objectives: Sinus venous thrombosis (SVT) is a rare complication of acute otitis media (AOM) with acute mastoiditis (AM), which during recent years has been associated with Fusobacterium necrophorum (Fn) infection. Our objective was to review clinical, microbiologic, and hematologic features of paediatric otogenic SVT, with a specific focus on the role of Fn. Methods: A retrospective database review in a tertiary paediatric hospital between 2000-2019. Results: Fifty children aged 6-155 months were treated for AM with SVT. Forty-seven (94%) underwent cortical mastoidectomy. Forty-six children received low-molecular-weight heparin (LMWH). Follow-up imaging revealed recanalisation in 92% of cases. No long-term neurologic or haematologic complications were observed. Since 2014, when anaerobic cultures and PCR were routinely used in our institute, Fn was isolated from 15/21 children with SVT. Their time to recanalisation was longer, and the rate of lupus anticoagulant antibodies (LAC) was higher than in the 6 non-Fn patients. Children positive for LAC also had a longer time to recanalisation. Conclusions: Fn is a common pathogen in AM with SVT; its thrombogenic role was demonstrated by a higher prevalence of LAC and a longer time to recanalisation.

Heat-killed Lactobacillus acidophilus mediates Fusobacterium nucleatum induced pro-inflammatory responses in epithelial cells.

Probiotics is widespreadly used nowadays. However, the safety issue with the use of live probiotics is still a matter of contention. In recent years, an expanding body of evidence supports the beneficial role of heat-killed probiotics in the maintenance of systemic health, whereas the role of these heat-killed bacteria on periodontal health remains unclear. This study aimed to evaluate the effects of heat-killed probiotics on periodontal pathogen virulence and associated mechanisms. We demonstrated that heat-killed Lactobacillus acidophilus was able to coaggregate with Fusobacterium nucleatum, the bridging bacteria of oral biofilm, and inhibit the adhesion and invasion of F. nucleatum, leading to a subsequent elimination of pro-inflammatory cytokine production in oral epithelial cells. This coaggregation further caused a suppression of the virulence gene fap2 expression in F. nucleatum. Therefore, heat-killed L. acidophilus might downregulate the pro-inflammatory cytokine expression in epithelial cells via coaggregation with F. nucleatum and suppression of F. nucleatum fap2 expression, which was the first demonstration that heat-killed probiotics modulate periodontal disease pathogenesis via coaggregation. Collectively, this finding provides new evidence that heat-killed probiotics might exert beneficial effects to periodontal health by coaggregating with periodontal pathogens and modulating their virulence.

Knock down of BMSC-derived Wnt3a or its antagonist analogs attenuate colorectal carcinogenesis induced by chronic Fusobacterium nucleatum infection.

By establishing the Fusobacterium nucleatum (F. nucleatum) infected-bone mesenchymal stem cells (BMSCs) transplantation model in APCMin/+ mice, we investigated the role of BMSCs in the development of intestinal tumors induced by F. nucleatum. ApcMin/++F. nucleatum + BMSCs mice showed increased susceptibility to intestinal tumors and accelerated tumor growth. BMSCs could also enhance tumor-initiating capability, invasive traits after F. nucleatum infection in vitro, and tumorigenicity in a nude murine model. Mechanistically, BMSCs were recruited to the submucosa, migrated to the mucosal layer, and might activate the canonical Wnt/ß-catenin/TGIF axis signaling. Further mechanistic results illustrated increased production of the Wnt3a protein was found in ApcMin/++F. nucleatum + BMSCs mice, and BMSCs were likely the major source of Wnt3a. Intriguingly, a deletion of Wnt3a via BMSC interference or antagonist analogs led to a significantly attenuated capacity of ApcMin/++F. nucleatum mice to generate intestinal tumors. The findings suggest that BMSCs have the potential to migrate and accelerate F. nucleatum-induced colorectal tumorigenesis by modulating Wnt3a secretion; knockdown of BMSC-derived Wnt3a or antagonist analogs could attenuate carcinogenesis. Thus, Wnt3a might be a potential pharmaceutical target for the prevention and treatment of F. nucleatum-related colorectal cancer.

An immunocompetent patient with culture-negative multiple brain abscesses caused by Fusobacterium nucleatum.

The diagnosis and treatment of brain abscesses have advanced due to the utilization of modern microbiological and neurosurgical methods. Here we present a 49-year-old female patient presented with headache and neurological symptoms. Initial evaluation revealed multiple ring-enhanced brain lesions and a lung cavitary lesion initially suspected to represent a malignant process. Stereotactic aspiration provided the diagnosis of brain abscesses but yielded negative cultures. 16S ribosomal RNA analysis enabled the identification of Fusobacterium nucleatum. For ten weeks, the patient was treated with ceftriaxone and metronidazole. A marked clinical and radiological improvement was noted. Brain abscess is a severe intracranial infectious process with significant morbidity and mortality. Microbiological analysis is challenging due to the location of the infection, the broad spectrum of causative agents, and the low yield of cultures. Fusobacterium nucleatum is an anaerobic bacteria with a tendency to abscess formation and is isolated from 2% of brain abscesses. The utilization of 16S RNA analysis improves microbiological identification rates in brain abscesses, as in other infectious entities, enabling better pathogen characterization and more suitable treatment.

Interaction between Lactobacillus reuteri and periodontopathogenic bacteria using in vitro and in vivo (G. mellonella) approaches.

Periodontitis is a multifactorial inflammatory disease, and the major cause of tooth loss in adults. New therapies have been proposed for its treatment, including the use of probiotics such as Lactobacillus reuteri. The objective of this study was to evaluate the antimicrobial effects of L. reuteri: live, heat-killed and culture filtrate (cell-free supernatant), on periodontopathogenic bacteria (Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans) in vitro, as well as the in vivo survival curve, hemocyte density and microbial recovery using Galleria mellonella. For in vitro assays, all preparations reduced colony forming units of F. nucleatum, while only live L. reuteri reduced the growth of A. actinomycetemcomitans. All treatments reduced periodontopathogenic bacteria growth in vivo. The treatment with the supernatant increased the survival of larvae infected with F. nucleatum more than the treatment with live L. reuteri, and none of the treatments altered the survival of A. actinomycetemcomitans-infected larvae. In addition, the treatment with L. reuteri preparations did not alter the hemocyte count of F. nucleatum- and A. actinomycetemcomitans-infected larvae. This study demonstrated that L. reuteri preparations exerted antimicrobial effects and increased the survival of G. mellonella infected by F. nucleatum, although only live L. reuteri was able to reduce the growth of A. actinomycetemcomitans in vitro.

Septic Shock Caused by Fusobacterium Necrophorum after Sexual Intercourse during Recovery from Infectious Mononucleosis in an Adolescent: A Case Report.

BACKGROUND: Infectious mononucleosis (IM) develops after primary infection with Epstein-Barr virus. We report a case of septic shock from pelvic inflammatory disease caused by Fusobacterium necrophorum in an adolescent after sexual intercourse during recovery from IM. CASE: A 17-year-old girl with a 7-day history of fever was diagnosed with IM. During follow-up, she developed lower abdominal pain and high fever after sexual intercourse and was transferred to our hospital. She was in shock and had a right ovarian abscess. Emergency laparotomy, drainage, and right adnexectomy were performed. F necrophorum was subsequently detected in blood and abscess cultures.

Fusobacterial brain abscess caused by paradoxical embolization associated with Ebstein's anomaly in an adult patient: A case report.

Brain abscess remains a life-threatening condition. Here, we are reporting a case of brain abscess due to Fusobacterium nucleatum in a previously known case of Ebstein anomaly. A 44-year-old male presented with the complaints of headache, and fever. Cerebral imaging revealed parieto-occipital (PO) abscess. The abscess was drained and culture showed growth of Fusobacterium nucleatum. This report illustrates the importance of considering anaerobes as the cause of brain abscess, underscores the usefulness of MALDI, which facilitated the selection of appropriate and prompt adjuvant antibiotic therapy and a favourable outcome.

Fusobacterium necrophorum, a major provider of sinus thrombosis in acute mastoiditis: A retrospective multicentre paediatric study.

OBJECTIVE: To evaluate in children the clinical severity and evolution of otogenic lateral sinus thrombosis (OLST) due to Fusobacterium necrophorum compared with other bacterial otogenic thrombosis and propose a specific management flowchart for Fusobacterium OLST. DESIGN: A retrospective multicentre cohort study. SETTINGS: Four French ENT paediatric departments. PARTICIPANTS: A total of 260 under 18 years old admitted for acute mastoiditis were included. Initial imaging was reviewed to focus on complicated mastoiditis and 52 OLST were identified. Children were then divided into two groups according to bacteriological results: 28 in the "OLST Fusobacterium group" and 24 in the "OLST other bacteria group". RESULTS: There was a significant association between F necrophorum and OLST (P < .001). When compared to the OLST other bacteria group, children in the OLST Fusobacterium group were significantly younger (61 months vs 23 months, P < .01) and had a more severe clinical presentation: higher CRP (113 mg/L vs 175.7 mg/L, P = .02) and larger subperiosteal abscess (14 mm vs 21 mm, P < .01). Medical management was also more intensive in the OLST Fusobacterium group than in the OLST other bacteria group: increased number of conservative surgeries (66.7% vs 92.9%, P = .03) and longer hospital stay (13.7 days vs 19.8 days, P = .02). At the end of follow-up, the clinical course was good in both groups without any neurological sequelae. CONCLUSIONS: Thrombotic complications are very frequent in case of Fusobacterium mastoiditis and clinicians should be aware of the initial severity of the clinical presentation. Under appropriate management, the clinical course of Fusobacterium OLST is as good as that of other bacterial otogenic thrombosis.

Immunological Pathways Triggered by Porphyromonas gingivalis and Fusobacterium nucleatum: Therapeutic Possibilities?

Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are Gram-negative anaerobic bacteria possessing several virulence factors that make them potential pathogens associated with periodontal disease. Periodontal diseases are chronic inflammatory diseases of the oral cavity, including gingivitis and periodontitis. Periodontitis can lead to tooth loss and is considered one of the most prevalent diseases worldwide. P. gingivalis and F. nucleatum possess virulence factors that allow them to survive in hostile environments by selectively modulating the host's immune-inflammatory response, thereby creating major challenges to host cell survival. Studies have demonstrated that bacterial infection and the host immune responses are involved in the induction of periodontitis. The NLRP3 inflammasome and its effector molecules (IL-1ß and caspase-1) play roles in the development of periodontitis. We and others have reported that the purinergic P2X7 receptor plays a role in the modulation of periodontal disease and intracellular pathogen control. Caspase-4/5 (in humans) and caspase-11 (in mice) are important effectors for combating bacterial pathogens via mediation of cell death and IL-1ß release. The exact molecular events of the host's response to these bacteria are not fully understood. Here, we review innate and adaptive immune responses induced by P. gingivalis and F. nucleatum infections and discuss the possibility of manipulations of the immune response as therapeutic strategies. Given the global burden of periodontitis, it is important to develop therapeutic targets for the prophylaxis of periodontopathogen infections.

Is a fusobacterium nucleatum infection in the colon a risk factor for colorectal cancer?: a systematic review and meta-analysis protocol.

BACKGROUND: Despite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer. METHODS: This systematic review will include observational studies (cohort, case-control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting. DISCUSSION: Deepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic. SYSTEMATIC REVIEW REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

[CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses]. / CME: Fusobacterium nucleatum/naviforme ­ eine seltene, aber nicht zu unterschätzende Ursache für pyogene Leberabszesse.

CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses Abstract. Pyogenic liver abscesses belong to the most common abdominal infections. Beside the most common pathogens, also rare forms like Fusobacteria, which can also be part of the natural oropharyngeal and enteral microbiome, may be considered to cause severe forms of abscesses of the liver. Since they may be more difficult to detect, they could become a challenge during diagnosis and therapy.

A Unique Case of Concurrent Long Bone Osteomyelitis and Empyema Caused by Fusobacterium nucleatum.

We describe a patient presenting with constitutional symptoms, poor oral hygiene and leg swelling who was diagnosed with Fusobacterium nucleatum osteomyelitis of femur and empyema. Long bone osteomyelitis is rarely caused by this microorganism. This unusual case was successfully managed with drainage and antimicrobial therapy.

Biochemical characterization of a recombinant Lactobacillus acidophilus strain expressing exogenous FomA protein.

In previous research, to combine the immunogenicity of Fusobacterium nucleatum (F. nucleatum) and the probiotic properties of Lactobacillus acidophilus (L. acidophilus), we constructed a FomA-expressing L. acidophilus strain and assessed its immunogenicity. Our findings indicated that oral administration of the recombinant L. acidophilus strain reduced the risk of periodontal infection by Porphyromonas gingivalis (P. gingivalis) and F. nucleatum. However, because the exogenous FomA is an heterologous protein for the original bacterium, in this study, we assessed whether the biochemical characteristics of the recombinant L. acidophilus strain change due to the expression of the exogenous FomA protein. OBJECTIVES: To test the biochemical characteristics of a recombinant L. acidophilus strain expressing exogenous FomA and assess its antibiotic sensitivity. DESIGNS: We assessed the colony morphology, growth, acid production, and carbohydrate fermentation abilities of the recombinant L. acidophilus strain. In addition, we tested the adhesive ability and antimicrobial activity of the recombinant and assessed its antibiotic sensitivity through a drug susceptibility test. RESULTS: The experimental results showed that the colony and microscopic morphology of the recombinant L. acidophilus strain was consistent with the original strain, and the recombinant strain grew well when cultured under aerobic or anaerobic conditions, exhibiting a growth rate that was identical to that of the standard strain. Similarly, the supernatants of the recombinant L. acidophilus can inhibit the growth of E. coli and P. gingivalis at different concentrations, and the recombinant strain displayed essentially the same drug sensitivity profile as the original L. acidophilus. However, to our surprise, the recombinant strains exhibited a greater adhesion ability than the reference strain. CONCLUSIONS: Our study demonstrated that, in addition to an increased adhesion ability, the recombinant L. acidophilus strain maintained the basic characteristics of the standard strain ATCC 4356, including antibiotic sensitivity. Thus, the recombinant strains have great potential to be utilized as a safe and effective periodontitis vaccine in the future.

Liver abscess due to Fusobacterium species detected on ultrasonography: a case report.

An oral infection harboring Fusobacterium species can gain entrance to the liver via hematogenous spread in the form of septic embolus, and can thereby cause abscesses. Such spread, described as Lemierre syndrome, is life threatening. We present such a case history of a man in his mid-40s, who presented with infection and Fusobacterium liver abscess with an acute fulminant disease course. The initial diagnosis was arrived at by ultrasound imaging and blood investigations. He was treated with antibiotics, ultrasound-guided liver abscess drainage, and extraction of the infected molar tooth. He was discharged 6 weeks after admission. To date, there have been no reports describing the ultrasound images of a Fusobacterium liver abscess in detail. Hence, we herein present the ultrasound images of a Fusobacterium liver abscess.

Fusobacterium emphysematous pyomyositis with necrotizing fasciitis of the leg presenting as compartment syndrome: a case report.

BACKGROUND: Fusobacterium necrophorum is a common agent of disease in humans, but the occurrence of primary infections outside the head and neck area is extremely rare. While infection with Fusobacterium necrophorum has a rather benign course above the thorax, the organism is capable of producing very severe disease when located in unusual sites, including various forms of septic thrombophlebitis. No infections of the leg have been documented before; thus, antibiotic coverage for Fusobacterium is currently not recommended in this area. CASE PRESENTATION: A 50-year-old homeless African-American man presented complaining of severe pain in his right lower extremity. A clinical workup was consistent with emphysematous pyomyositis and compartment syndrome; he received limb-saving surgical intervention. The offending organism was identified as Fusobacterium necrophorum, and the antibiotic coverage was adjusted accordingly. CONCLUSIONS: Bacteria typically involved in necrotizing infections of the lower extremity include Group A ß-hemolytic Streptococcus, Clostridium perfringens, and common anaerobic bacteria (Bacteroides, Peptococcus, and Peptostreptococcus). This case report presents a case of gas gangrene of the leg caused by Fusobacterium necrophorum, the first such case reported. Fusobacterium should now be included in the differential diagnosis of necrotizing fasciitis of the extremities.

Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract.

Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.