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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Fusobacterial infections: clinical spectrum and incidence of invasive disease.

OBJECTIVES: Clinically significant infections caused by members of the genus Fusobacterium are rare. We sought to describe the spectrum of clinical disease and epidemiology of these conditions presenting to an acute hospital over a five year period. METHODS: Clinical records relating to consecutive laboratory isolates of Fusobacterium species were reviewed and cases classified according to pre-specified definitions of primary site and invasive infection. RESULTS: 78 Fusobacterium isolates were identified, 25 of which were associated with invasive disease, most commonly in men (76% of cases). Invasive Fusobacterium necrophorum infection of the head and neck was not observed in patients over 50. Invasive intra-abdominal disease was not observed amongst those under 60. 2 cases of Fusobacterium nucleatum bacteraemia were identified in neutropenic children. One retroperitoneal abscess may have represented secondary infection due to periodontitis. Obstetric infections were the most common clinical syndromes associated with isolates from the female genital tract. The incidence of invasive head and neck disease in the population aged 15-50 was 6.7 per million/year. There were no deaths. CONCLUSIONS: Invasive fusobacterial infections are rare, affect distinct patient groups and are associated with good clinical outcomes in the majority of cases.

Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre's syndrome.

Human infection with Fusobacterium necrophorum usually involves F. necrophorum subsp. funduliforme rather than F. necrophorum subsp. necrophorum, which is a common pathogen in animals. Lemierre's syndrome, or postanginal sepsis, is the most common life-threatening manifestation. Tonsillitis is followed by septic thrombophlebitis of the internal jugular vein and then a septicemia with septic emboli in lungs and other sites. Recent evidence suggests that F. necrophorum can be limited to the throat and cause persistent or recurrent tonsillitis. F. necrophorum is unique among non-spore-forming anaerobes, first for its virulence and association with Lemierre's syndrome as a monomicrobial infection and second because it seems probable that it is an exogenously acquired infection. The source of infection is unclear; suggestions include acquisition from animals or human-to-human transmission. Approximately 10% of published cases are associated with infectious mononucleosis, which may facilitate invasion. Recent work suggests that underlying thrombophilia may predispose to internal jugular vein thrombophlebitis. Lemierre's syndrome was relatively common in the preantibiotic era but seemed to virtually disappear with widespread use of antibiotics for upper respiratory tract infection. In the last 15 years there has been a rise in incidence, possibly related to restriction in antibiotic use for sore throat.