Leukotoxin production by Fusobacterium necrophorum strains in relation to severity of liver abscesses in cattle.

Fusobacterium necrophorum, a Gram-negative anaerobe, is the primary etiologic agent of liver abscesses of beef cattle. The bacterium, a member of the microbial community of the rumen, travels to the liver via portal circulation to cause abscesses. The severity of liver abscesses vary from mild with one or two small abscesses to severe with medium to large multiple abscesses. Leukotoxin, a secreted protein, is the critical virulence factor involved in the infection. Our objective was to compare leukotoxin production between strains of F. necrophorum isolated from mild and severe liver abscesses collected from slaughtered cattle. The quantification of leukotoxin was based on assays to measure cytotoxicity and protein antigen concentration. One-hundred strains, 50 from mild and 50 from severe abscesses, were utilized in the study. Cell-free supernatants were prepared from cultures grown in anaerobic broth at 9 and 24 h incubations. The leukotoxic activity was quantified by measuring cytotoxicity based on the release of lactic dehydrogenase from bovine lymphocyte cells, BL3, treated with the culture supernatant. Leukotoxin protein concentration was quantified by a sandwich ELISA assay with a leukotoxin-specific monoclonal antibody as the capture antibody. The leukotoxin activity and concentration were highly variable among the strains within each severity of liver abscesses. Although the leukotoxic activity was unaffected by incubation time, leukotoxin protein concentration was consistently higher at 24 h compared to 9 h incubation. Strains from severe liver abscesses had significantly higher leukotoxic activity and higher protein concentration compared to strains from mild liver abscesses (P < 0.0001) at both 9 and 24 h culture supernatants. Across all strains, the correlation coefficients between leukotoxic activity and leukotoxin concentration at 9 and 24 h were 0.14 (P = 0.17) and 0.47 (P < 0.0001), respectively. In conclusion, strains isolated from severe liver abscesses had significantly higher leukotoxic activities and leukotoxin protein concentrations compared to strains isolated from mild liver abscesses.

Geographical differences in tonsillar carriage rates of Fusobacterium necrophorum - A cross-sectional study in Sweden and Zambia.

While Fusobacterium necrophorum historically has been considered normal tonsillar flora, recent studies from Europe and the US have suggested that carriage occur transiently in adolescence and young adulthood. However, no studies originating from Africa exist. In this cross-sectional study of tonsillar carriage of F. necrophorum, we aimed to investigate geographical differences in tonsillar carriage rates of F. necrophorum in healthy participants aged 15-25 years in Sweden and Zambia and further investigate the age distribution of tonsillar carriage in Zambia. Specimens were obtained by tonsillar swabs and analyzed with real-time PCR for F. necrophorum. In participants aged 15-25 years, tonsillar carriage was more common in Sweden 21/100 (21%) than in Zambia 6/192 (3%), p < 0.001. In Zambian participants aged above 25 years tonsillar carriage was rare 1/76 (1%). In conclusion, the high rate of tonsillar carriage in participants aged 15-25 years in Sweden has implications on the interpretation of tonsillar findings in patients with pharyngotonsillitis. Interestingly, a geographical difference was found with tonsillar carriage rarely identified in Zambia.

Unusual case of necrotizing pneumonia caused by Fusobacterium nucleatum complicating influenza a virus infection.

We report a rare case of Fusobacterium nucleatum necrotizing pneumonia following an influenza viral infection. This rare bacterial lung infection can have severe complications such as respiratory failure and septic shock, so early recognition and treatment are necessary.

Surgical intervention for acute mastoiditis: 10 years experience in a tertiary children hospital.

PURPOSE: To evaluate the clinical course of children with acute mastoiditis (AM) who required surgical intervention. MATERIAL AND METHODS: Clinical and biochemical characteristics at the moment of hospital admission were reviewed for patients who required surgery for AM. Children who were successfully managed conservatively during the last 3 years of study were chosen as a comparison group. RESULTS: During 2008-2017, 570 children were admitted with AM: 82(14%) underwent cortical mastoidectomy, including 31(38%) with decompression of epidural space and sigmoid sinus. The comparison group consisted of 167 children with AM who did not require surgery. The surgical group had a higher rate of acute otitis media before admission. At the time of hospital admission, the surgical group had a higher rate of prolonged fever, otorrhea, and sub-periosteal abscess. Their average temperature, WBC, neutrophil count, and CRP were significantly higher (39.2 vs. 37.9°. C, 20 K vs. 16.5 K, 67 vs. 55.8 percent, 17 vs. 8.8, respectively, p = 0.0001). Fusobacterium necrophorum was the most common pathogen in the surgical group (50%), and group A streptococcus in the comparison group (22%). Sub-periosteal abscess, sinus venous thrombosis, and epidural involvement were diagnosed in 95, 35, and 38 percent of patients, respectively. Average length of IV antibiotic treatment was 20 days in operated children, compared to 5.6 days in the comparison group (p = 0.0001). Since 2013, a significantly higher percentage of children were diagnosed with Fusobacterium mastoiditis (p = 0.0001) who required surgery (p = 0.008). CONCLUSION: In children with AM presenting with, high fever, leukocytosis, elevated CRP, and sub-periosteal abscess, early CT and surgical intervention were frequently required. The increase in Fusobacterium infection might be an explanation for the increase in complicated AM requiring surgery.

Epidemiology and clinical outcomes of patients with Fusobacterium bacteraemia.

This 10-year retrospective study assessed the epidemiology and outcomes of patients with Fusobacterium bacteraemia (FB) at a tertiary-care hospital in the USA - this is the second study focusing on FB in adults to be conducted in the USA in 30 years. Demographic, clinical, laboratory, treatment, and outcome data were collected and statistically analysed. Nineteen patients with FB were identified, representing 0·11% of bacteraemia cases. Mean age was 58·6 years with equal gender distribution. Common comorbidities included cardiovascular disease (CVD) and immunosuppression. Thirty-day mortality was 21·1%, and 68·4% of FB patients required intensive care unit (ICU) admission. Elevated creatinine levels and mental status changes were associated with higher mortality (P = 0·0181 and 0·0374, respectively). CVD, diabetes, and ICU admission were associated with increased length of hospital stay (P = 0·0017, 0·0010, and 0·0379, respectively). The prevalence of FB at our hospital was very low, with poor outcomes associated with increased creatinine level, mental status changes, CVD, diabetes and ICU admission.

Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization.

Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with Fusobacterium nucleatum (F. nucleatum, Fn) infection. In this study, we explored the role of F. nucleatum in the CRC metastasis. Our results showed that the abundance of F. nucleatum was enriched in the feces and tumors of patients with CRC and tended to increase in stage IV compared to stage I in patients with metastatic CRC. Tumor-derived CCL20 activated by F. nucleatum not only increases CRC metastasis, but also participates in the reprograming of the tumor microenvironment. F. nucleatum promoted macrophage infiltration through CCL20 activation and simultaneously induced M2 macrophage polarization, enhancing the metastasis of CRC. In addition, we identified using database prediction and luciferase activity hat miR-1322, a candidate regulatory micro-RNA, could bind to CCL20 directly. F. nucleatum infection decreased the expression of miR-1322 by activating the NF-κB signaling pathway in CRC cells. In conclusion, F. nucleatum promotes CRC metastasis through the miR-1322/CCL20 axis and M2 polarization.

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.

Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence proteins.

BACKGROUND: Fusobacterium nucleatum is a gram-negative anaerobic species residing in the oral cavity and implicated in several inflammatory processes in the human body. Although F. nucleatum abundance is increased in inflammatory bowel disease subjects and is prevalent in colorectal cancer patients, the causal role of the bacterium in gastrointestinal disorders and the mechanistic details of host cell functions subversion are not fully understood. RESULTS: We devised a computational strategy to identify putative secreted F. nucleatum proteins (FusoSecretome) and to infer their interactions with human proteins based on the presence of host molecular mimicry elements. FusoSecretome proteins share similar features with known bacterial virulence factors thereby highlighting their pathogenic potential. We show that they interact with human proteins that participate in infection-related cellular processes and localize in established cellular districts of the host-pathogen interface. Our network-based analysis identified 31 functional modules in the human interactome preferentially targeted by 138 FusoSecretome proteins, among which we selected 26 as main candidate virulence proteins, representing both putative and known virulence proteins. Finally, six of the preferentially targeted functional modules are implicated in the onset and progression of inflammatory bowel diseases and colorectal cancer. CONCLUSIONS: Overall, our computational analysis identified candidate virulence proteins potentially involved in the F. nucleatum-human cross-talk in the context of gastrointestinal diseases.

Lemierre's syndrome variant of the gut.

Infectious suppurative thrombophlebitis of the portal venous system, referred to as pylephlebitis, is a rare complication of intra-abdominal inflammatory processes. Advances in diagnostics and antibiotics have improved survival, but mortality remains remarkably high even in the most recent literature. The majority of patients have concomitant bacteraemia on presentation most commonly with typical gastrointestinal (GI) organisms. On rare occasion, patients have culture positive Fusobacterium, which has recently been associated with occult GI and genitourinary malignancies. Here, we describe a patient presenting with pylephlebitis and Fusobacterium bacteraemia who responded well to medical therapy, review pertinent literature and discuss the benefits of screening endoscopy in this patient population.

Lemierre syndrome.

Lemierre syndrome is a disease that presents with oropharyngeal infection, sepsis, internal jugular vein thrombosis, and septic emboli with the Gram-negative organism Fusobacterium necrophorum cultured as the etiologic agent. Clindamycin, metronidazole and ampicillin-sulbactam are effective antibiotic treatments, although the length of treatment has not been firmly established. The syndrome is seen less frequently in the current age of antibiotics. It is important, however, that physicians be aware of the syndrome as initiation of prompt antibiotic therapy, including anaerobic coverage, is essential for avoiding morbidity and mortality. We describe a case of Lemierre syndrome.

Clival osteomyelitis and hypoglossal nerve palsy--rare complications of Lemierre's syndrome.

An increasingly reported entity, Lemierre's syndrome classically presents with a recent oropharyngeal infection, internal jugular vein thrombosis and the presence of anaerobic organisms such as Fusobacterium necrophorum. The authors report a normally fit and well 17-year-old boy who presented with severe sepsis following a 5-day history of a sore throat, myalgia and neck stiffness requiring intensive care admission. Blood cultures grew F. necrophorum and radiological investigations demonstrated left internal jugular vein, cavernous sinus and sigmoid sinus thrombus, left vertebral artery dissection and thrombus within the left internal carotid artery. Imaging also revealed two areas of acute ischaemia in the brain, consistent with septic emboli, skull base (clival) osteomyelitis and an extensive epidural abscess. The patient improved on meropenem and metronidazole and was warfarinised for his cavernous sinus thrombosis. He has an on-going left-sided hypoglossal (XIIth) nerve palsy.

Studies on fusobacteria associated with periodontal diseases.

The physiological and metabolic characteristics of representative isolates of the various subspecies of Fusobacterium nucleatum were investigated by growing them in continuous culture in chemically-defined, media. Behaving almost identically, these organisms were found to obtain energy from the fermentation of simple carbohydrates such as glucose or fructose or from the fermentation of certain amino acids, free or in the form of small peptides. The latter can be attacked by aminopeptidase activity which was shown to be essential for the growth of the organism in an environment lacking fermentable carbohydrate and free amino acids but replete with small peptides. This metabolic versatility may explain the presence of F. nucleatum in both supra- and sub-gingival dental plaque and why it is often found together with organisms such as Porphyromonas gingivalis which display powerful endopeptidase activities. Using the technique of allozyme electrophoresis, the current subspeciation of F. nucleatum was shown to be of doubtful validity and evidence, based upon physiological and metabolic properties, for differences in pathogenicity between isolates was not detected. While this organism is a member of various bacterial consortia associated with periodontal diseases, its contribution to the disease process remains unclear.

Extra-corporeal membrane oxygenation in a patient with Fusobacterium sepsis: a case report and review of literature.

An adolescent female was admitted to the pediatric intensive care unit in septic shock. She developed multisystem organ dysfunction including pancreatitis with myocardial dysfunction and hemodynamic instability unresponsive to medical management necessitating veno-arterial extracorporeal support. Streptococcus Constellata and Fusobacterium necrophorum were isolated from blood cultures. This is the first report of extra-corporeal cardiac support in fusobacterium sepsis.

Animal bite-associated infections: microbiology and treatment.

Human and animal bites may lead to serious infection. The organisms involved tend to originate from the oral cavity of the offending biter, as well as the environment where the injury occurred. A variety of aerobic as well as anaerobic organisms have been isolated from bite wounds, with infection ranging from localized cellulitis to systemic dissemination, leading to severe disease ranging from abscess to bone and joint infection, to endocarditis and brain abscess. Immediate wound management, including recognition of the most commonly associated infectious pathogens, and judicious use of empiric antibiotics are crucial in providing the best care after a bite. Here, we discuss the common animal bite associated infections, and provide the most up to date information regarding their management.