BACKGROUND: Legionella pneumonia is one of the most severe types of atypical pneumonia, impairing multiple organ systems, posing a threat to life. Diagnosing Legionella pneumonia is challenging due to difficulties in culturing the bacteria and limitations in immunoassay sensitivity and specificity.
METHODS: This paper reports a rare case of sepsis caused by combined infection with Legionella pneumophila and Fusobacterium necrophorum, leading to respiratory failure, acute kidney injury, acute liver injury, myocardial damage, and electrolyte disorders. In addition, we systematically reviewed literature on patients with combined Legionella infections, analyzing their clinical features, laboratory results and diagnosis.
CONCLUSIONS: For pathogens that require prolonged incubation periods and are less sensitive to conventional culturing methods, metagenomic next-generation sequencing (mNGS) can be a powerful supplement to pathogen screening and plays a significant role in the auxiliary diagnosis of complex infectious diseases.

We described a case of a 24-year-old man with multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260. This is the first described case of Lemierre\'s syndrome with multiple organ failure due to F. necrophorum subsp. funduliforme F1260 in an adult in China. Our study highlights that there may be a risk of misdiagnosis based solely on typical manifestations of internal jugular vein thrombophlebitis, metastatic lesions, and F. necrophorum isolated from blood cultures or normally sterile sites. Clinicians should be cognizant of the potential utility of metagenomic next-generation sequencing in facilitating early pathogen detection in severe infections, thus enabling timely and appropriate administration of antibiotics to reduce mortality rates and improve prognosis.

Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.

Fusobacterium necrophorum (F. necrophorum) infection is rare in pediatrics. In addition, the detection time of F. necrophorum by blood culture is long, and the positive rate is low. Infection with F. necrophorum bacilli usually follows rapid disease progression, resulting in high mortality. In previous reports of F. necrophorum-related cases, the most dangerous moment of the disease occurred after the appearance of Lemierre\'s syndrome. We report an atypical case of a 6-year-old female patient who developed septic shock within 24 h of admission due to F. necrophorum infection in the absence of Lemierre\'s syndrome. F. necrophorum was identified in a blood sample by metagenomics next-generation sequencing (mNGS) but not by standard blood culture. The patient was finally cured and discharged after receiving timely and effective targeted anti-infection treatment. In the present case study, it was observed that the heightened virulence and invasiveness of F. necrophorum contribute significantly to its role as a primary pathogen in pediatric septic shock. This can precipitate hemodynamic instability and multiple organ failure, even in the absence of Lemierre\'s syndrome. The use of mNGS can deeply and rapidly identify infectious pathogens, guide the use of targeted antibiotics, and greatly improve the survival rate of patients.

BACKGROUND: Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can lead to diagnostic difficulties.
METHODS: We report a case of F. necrophorum lung abscess diagnosed by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF).
RESULTS: BALF-NGS detected F. necrophorum, guiding subsequent targeted antibiotic therapy. With active drainage and metronidazole treatment, the patient\'s condition was effectively treated.
CONCLUSIONS: BALF-NGS is a valuable tool for the rapid diagnosis of infections caused by difficult-to-culture bacteria. It played a decisive role in the early identification of F. necrophorum, enabling timely and targeted antibiotic intervention. Early diagnosis and appropriate treatment are crucial for the management of F. necrophorum pneumonia.

UNASSIGNED: To understand the clinical features, diagnosis and treatment of Lemierre syndrome (LS), a high-risk and low-prevalence infectious disease.
UNASSIGNED: We present the severe LS case that was diagnosed using metagenomic next-generation sequencing (mNGS) in our hospital, and systematically summarized the diagnosis and treatment strategies of patients that reported LS from 2006 to 2022.
UNASSIGNED: The 24-year-old patient in our hospital suffered from cranial nerve paralysis, a neurological complication rarely seen in LS cases. The causative agent (Fusobacterium necrophorum, Fn) of this patient was only detected by mNGS tests, and the reads number of Fn detected by plasma mNGS tests was decrease as the patients gradually improved, indicating plasma mNGS is valuable in monitoring treatment efficacy. Although most of the cases retrieved from the literature showed typical symptoms, such as a history of sore throat, septic emboli, and internal jugular vein thrombosis, clinical manifestations were still relatively heterogeneous (eg, diversity of predisposing factors and pathogens, differences in pulmonary imaging features).
UNASSIGNED: We summarized the clinical presentation, diagnosis, treatment, and regression of 17 symptomatic cases reported LS to provide clinicians with knowledge about this rare but fatal disease. mNGS assays should be considered as early as possible to identify the responsible pathogens for acute and critically ill patients with suspected infections in order to implement accurate and effective treatment.

A 62-year-old African American man with a history of avascular necrosis (AVN) of the right hip joint presented with severe right hip pain, dyspnea, fever, tachycardia, and hypertension. Computed tomography (CT) scan showed bilateral airspace opacities with a mild tree-in-bud nodularity in the left lower lobe. Ultrasonography of the lower extremities revealed a deep venous thrombus (DVT) in the right deep veins. Blood cultures grew Fusobacterium necrophorum. CT and magnetic resonance imaging showed right hip joint destruction and septic arthritis. The patient had a complicated hospital course leading to total hip arthroplasty with antibiotic-impregnated cementing.

OBJECTIVE: Fusobacterium necrophorum causes bovine hepatic abscess, foot rot, mastitis, and endometritis. The 43 kDa outer membrane protein (43 K OMP) of F. necrophorum is a porin protein that plays an important role in infections by this bacterium, but the biological function and the pathogenesis of this protein are largely unknown.
METHODS: In this study, we investigated the role of the 43 K OMP in bacterial infection of bovine mammary epithelial cells (MAC-T cells) by Tandem Mass Tag proteomic analysis. The RAW264.7 cells were incubated with recombinant 43 K OMP (12.5 μg/mL) for 2 h, 4 h, 6 h, and 12 h, and then the inflammatory related protein and inflammatory cytokine production were measured by Western blot analysis and ELISA, the mRNA expression levels of inflammatory cytokine were measured by Real-Time PCR.
RESULTS: Proteomic analysis results demonstrated there were 224 differentially expressed proteins in the MAC-T cells stimulated with the 43 K OMP compared with control, and 118 proteins were upregulated and 106 proteins were downregulated. These differentially expressed proteins were mainly involved in NF-kappa B signaling, bacterial invasion of epithelial cells, cell adhesion, complement and coagulation cascades. The top six differentially expressed proteins were; MMP9, PLAU, STOM, PSMD13, PLAUR, and ITGAV, which were involved in a protein-protein interaction network. Furthermore, TLR/MyD88/NF-κB pathway related proteins and inflammatory cytokines (IL-6, TNF-α, and IL-1β) were assessed by Western blot analysis and ELISA. Results showed the 43 K OMP to enhance the expression of TLR4 protein at 2 h (P < 0.01) and the MyD88 protein at 4 h (P < 0.05) post-stimulation, and to decrease IκBα expression at 4 h, 6 h and 12 h (P < 0.05) post-infection, as well as induce phosphorylation at Ser536 (P < 0.01). Levels of IL-6, IL-1β, and TNF-α in the supernatants of mouse macrophages were increased (P < 0.05), as were mRNA expression levels of IL-6, IL-1β, and TNF-α (P < 0.05), while IL-4 mRNA expression was decreased (P < 0.05).
CONCLUSIONS: Taken together, these results suggested the important role for 43 K OMP in F. necrophorum infection, promoting the production of pro-inflammatory cytokines (IL-6 and TNF-α) by activation of the TLR/MyD88/NF-κB pathway. These findings provided a theoretical basis for a better understanding of the pathogenesis of F. necrophorum infection.

UNASSIGNED: Fusobacterium necrophorum is an anaerobic Gram-negative bacterium that can lead to opportunistic infections, including Lemierre\'s syndrome and less common presentations of metastatic diseases. However, liver abscesses infected by Fusobacterium necrophorum in clinical settings are rarely reported, particularly in people with normal immune function.
UNASSIGNED: A 35-year-old Chinese man was admitted with hyperthermia and abdominal pain that had persisted for three days. The patient continued to have a fever with a maximum temperature of 39.8 °C during hospitalization. Computed Tomography revealed multiple low-density lesions in the liver, which were diagnosed as liver abscesses caused by Fusobacterium necrophorum infection through blood culture and anaerobic liver abscess fluid culture. After simple local percutaneous abscess drainage and effective anti-infective therapy, the patient achieved complete remission.
UNASSIGNED: Results of our literature search query revealed rare reports of liver abscesses infected by Fusobacterium necrophorum. We recommend that Fusobacterium necrophorum infection be considered in diagnosis special situations of liver abscess.

Fusobacterium necrophorum is the main pathogen inducing bovine foot rot. The infected site is often accompanied by a strong inflammatory response, but the specific inflammatory regulatory mechanism remains unclear.
A cow skin explants model was established to elucidate the mechanism of F. necrophorum bacillus causing foot rot in cows, and to provide reference for future clinical practice.
Cow intertoe skin explants were cultured in vitro, and F. necrophorum bacteria solution and nuclear factor-κB (NF-κB) inhibitor BAY 1-7082 were added to establish an in vitro infection model. Hematoxylin and eosin staining, terminal - deoxynucleotidyl transferase mediated nick end labeling, and immunohistochemistry were used to detect the pathological changes of the skin explants infected with F. necrophorum, the degree of tissue cell apoptosis, and the expression of the apoptosis-related protein Caspase-3, respectively. RT-qPCR, Western blot, and ELISA were used to detect the activation of the NF-κB pathway and inflammatory cytokines by F. necrophorum.
The intertoe skin structure of cows infected with F. necrophorum changed with different degrees of inflammation, and the degree of tissue cell apoptosis was significantly increased (P < 0.01). In addition, infection with F. necrophorum significantly increased the phosphorylation level of IκBα protein and up-regulated the expression level of NF-κB p65. The high expression and transcriptional activity of NF-κB p65 significantly increased the expression and concentration of the inflammatory cytokines TNF-α, IL-1β, and IL-8, thus inducing the occurrence of an inflammatory response. However, inhibition of NF-κB p65 activity significantly decreased the expression of inflammatory factors in the intertoe skin of cows infected with F. necrophorum.
F. necrophorum activates NF-κB signaling pathway by increasing the expression of TNF-α, IL-1β, IL-8 and other inflammatory factors, leading to foot rot in dairy cows.