Search Results (240)

Among many metal ions in biological systems, iron plays a fundamental role. Transferrins are iron-binding glycoproteins responsible for transporting Fe³⁺ in vertebrate blood. Neisseria meningitidis, a Gram-negative pathogen causing meningitis, relies on iron for survival and acquires it from human transferrin (hTf) using two surface proteins, TbpA and TbpB. These proteins interact with hTf to form a ternary TbpA–TbpB–hTf complex, enabling iron capture from the host. The absence of an experimental crystal structure for this complex has hindered computational studies, a detailed understanding of Fe³⁺ dissociation, and designing efficient therapeutics. This study presents the first computational model of the ternary complex, its validation, and molecular dynamics simulations. Structural analyses revealed key electrostatic interactions regulating Fe³⁺ coordination and essential contact regions between proteins. The role of Lys359 from TbpA was investigated via QM/MM calculations by evaluating Fe³⁺ binding energies of isolated hTf, the ternary complex, and Lys359Ala, Lys359Arg, Lys359Asp mutant models. Results revealed that the proton transfer from Lys359 leads to disruption of Tyr517–Fe³⁺ coordination, facilitating iron transfer to the bacterial system. Natural bond orbital analysis confirmed this mechanism. The findings provide new molecular insight into N. meningitidis iron acquisition and identify Lys359 as a potential target for covalent inhibitor design, guiding the development of novel therapeutics against meningococcal infection. Full article

Bacterial meningitis involves complex molecular networks, including microRNA-mediated regulation of inflammatory responses; however, the specific role of Ovis aries microRNA-125b (oar-miR-125b) in this process remains poorly understood. In this study, using a lamb model of Enterococcus faecalis-induced meningitis, we observed significant downregulation of oar-miR-125b, which inversely correlated with its newly identified target, Tumor Necrosis Factor Superfamily Member 4 (TNFSF4). Dual-luciferase reporter assays confirmed that oar-miR-125b directly binds to the 3′ Untranslated Region (3′UTR) of TNFSF4 but not to the 3′UTRs of Kelch Like Family Member 31 (KLHL31) or NF-κB Inhibitor Interacting Ras Like 2 (NKIRAS2). Mechanistically, decreased oar-miR-125b expression relieves its repression of TNFSF4, leading to NF-κB pathway activation and blood–brain barrier disruption. Collectively, our results demonstrate that oar-miR-125b serves as a key anti-inflammatory regulator in bacterial meningitis by targeting TNFSF4 and constraining NF-κB signaling, highlighting its potential as a therapeutic target for attenuating neuroinflammation in meningitis. Full article

Multidrug-resistant (MDR) Streptococcus suis (S. suis) is a zoonotic pathogen capable of infecting pigs across all age groups, leading to conditions such as meningitis, arthritis, and endocarditis. In humans, infections can result in septic arthritis, meningitis, necrotizing fasciitis, and septicemia, which may be fatal. The absence of a complete genome sequence hinders comprehensive bioinformatic studies of MDR S. suis derived from pigs. In this study, we present the whole-genome sequence of MDR S. suis serotype 2 ST01 isolated from joint fluid samples obtained from pigs. Whole-genome analysis revealed that the ST01 chromosome carries 19 antibiotic resistance genes that confer resistance to major classes of antibiotic including aminoglycosides, tetracyclines, fluoroquinolones, lincosamides, polypeptide, and nitrofurans. Additionally, it contains 15 virulence factors associated with immune modulation, bacterial adherence, and stress survival. Whole-genome analysis identified 84 horizontal gene transfer elements in ST01 (comprising 28 genomic islands, 52 transposons, and 4 prophages), alongside mutations resulting in reduced virulence (302 instances) and loss of pathogenicity (34 instances). Furthermore, 18 antibiotic targets along with 21 lethal mutations were identified as potential targets for preventing, controlling, and treating infection caused by MDR S. suis serotype 2 ST01. In vivo infection experiments demonstrated that intraperitoneal inoculation with ST01 resulted in mortality among Kunming mice, with a median lethal dose (LD₅₀) of 5.62 × 10⁹ CFU/mL. Histopathological analysis revealed varying degrees of lesions in the infected organs of the mice. This study thus provides valuable insights into strategies aimed at combating S. suis infections and their transmission within swine populations. Full article

The development of sensitive and specific diagnostic methods for secondary bacterial meningitis remains an urgent challenge in neurosurgical and intensive care units. A combination of various clinical and biochemical parameters, as well as biomarkers and metabolites in cerebrospinal fluid (CSF), can be considered for constructing multivariate diagnostic models. In this study, 96 CSF samples from 53 patients with suspected secondary meningitis were analyzed. The first cohort, consisting of patients with sequelae of severe brain damage, included 7 patients (21 CSF samples) with and 29 patients (56 CSF samples) without secondary bacterial meningitis. The second cohort comprised patients after neurosurgical interventions, including 10 patients (12 CSF samples) with and 7 patients (7 CSF samples) without secondary bacterial meningitis. Combined group 1 with 33 CSF samples from patients with secondary bacterial meningitis and combined group 2 with 63 CSF samples from patients without secondary bacterial meningitis had statistically different cell and biochemical compositions and higher CSF concentrations of biomarkers (interleukin-6 and S100 protein) and lactate-containing aromatic metabolites in group 1. Univariate prognostic models constructed on 4-hydroxyphenyllactic, phenyllactic, and indole-3-lactic acids demonstrated outstanding AUC-ROC of more than 0.91. A multivariate model built on all biomarkers and metabolites resulted in AUC-ROC = 0.94 with a sensitivity of 0.94 and specificity of 0.86, and was found to be the most accurate method for the diagnosis of secondary bacterial meningitis. Full article

Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship. Full article

Background/Objectives: Meningoencephalitis (ME) is a life-threatening infectious disease; therefore, prompt and accurate diagnosis is lifesaving. Traditional diagnostic methods, such as culture, have several limitations related to sensitivity and specificity. Emerging multiplex ME-PCR panels are a comprehensive and rapid tool in a single test. The Bio-Speedy Meningitis/Encephalitis RT-qPCR MX-17 panel (Bioeksen R&D Technologies Inc., Turkey) enables testing for 17 targets. To evaluate the performance of the panel compared to clinical and CSF parameters. Methods: A total of 403 patients with a preliminary diagnosis of ME were reviewed between January 2019 and September 2023. Following revision, 72 patients with clinical, CSF, and laboratory findings were included. The tested panel was used to detect targeted pathogens in CSF samples. The 30-day survival rate and prolonged stay were analyzed. Results: The median CSF protein value was 59.5 mg/dL (14.2–1471 mg/dL) and glucose was 61.95 mg/dL (0.083–165 mg/dL). Forty-one (56.9%) ME panel results were positive, among which 38.9% (28) were viral and 19.4% (14) were bacterial. HHV-6 ranked first with a rate of 15.3%. The Bio-Speedy panel test results outperformed the CSF culture (p < 0.001). The correlation of the Bio-Speedy panel with impaired consciousness was statistically significant (p = 0.004). Six (8.3%) patients from the study group died within 30 days. Conclusions: Compared to traditional methods, Bio-Speedy panel was effective in identifying the causative agents of ME. The Bio-Speedy ME RT-qPCR MX-17 panel offers accurate detection of ME-causing pathogens. The implementation of the panel in clinical practice can impact patient management and improve outcomes. Full article

Background: Balamuthia mandrillaris is a free-living amoebic parasite that primarily causes rare opportunistic infections in immunocompromised hosts. Balamuthia amoebic encephalitis (BAE) is a rare yet severe parasitic infection affecting the central nervous system. It has an extremely low incidence in China but can have a mortality rate as high as 98%. The clinical manifestations of amebic infections are similar to those of bacterial and tuberculous meningitis, lacking specificity, which makes accurate diagnosis challenging in the clinical setting. Case Presentation: A 61-year-old immunocompetent woman experienced worsening headache and a moderate fever over the course of five days, initially treated as a common cold. On 25 February 2025, she exhibited behavioral abnormalities, dysphagia, and a high fever of 40.2 °C, which progressed to a coma. On 26 February, her cranial CT scan revealed multifocal hemorrhagic lesions in the right frontotemporoparietal lobes. The MRI revealed similar lesions with slight enhancement and herniation. She underwent an emergency decompressive craniectomy, yet her condition continued to deteriorate following the surgery. On 27 February, serum targeted next-generation sequencing (tNGS) detected B. mandrillaris. Additionally, metagenomic NGS (mNGS) of the cerebrospinal fluid (CSF) sample confirmed the presence on 28 February. Finally, B. mandrillaris was identified through a brain tissue biopsy on 3 March. However, due to the delayed diagnosis and lack of effective drugs, her condition rapidly deteriorated and became irreversible. Her family ultimately chose to withdraw treatment. Conclusions: This study highlights the application of NGS for early diagnosis of patients with severe CNS infection. Both tNGS and mNGS can be considered for the rapid detection of rare or novel pathogens and for facilitating diagnosis. Full article

Introduction: Brain abscess is defined as a suppurative collection resulting from hematogenous dissemination as an extension from otorhinolaryngologic infectious foci, or secondary to cranial trauma and neurosurgical procedures. Its evolution follows four histopathological stages, the most severe complication being intraventricular rupture, which is associated with extremely high mortality. Central nervous system infections caused by multidrug-resistant (MDR/XDR) Acinetobacter baumannii are rare but severe, significantly limiting therapeutic options due to the reduced penetration of the blood-brain barrier by active antimicrobial agents. Case report: We report the case of a 48-year-old patient with a history of hemorrhagic stroke treated surgically, who was admitted for fever, severe headache, and vomiting. On admission, lumbar puncture confirmed bacterial meningitis, with isolation of A. baumannii susceptible only to colistin. Brain magnetic resonance imaging revealed a postoperative cerebellar abscess. Initial empirical therapy consisted of meropenem and vancomycin, subsequently adjusted according to the susceptibility profile to cefiderocol, intravenous and intrathecal colistin, combined with ampicillin/sulbactam and minocycline. The clinical course was favorable with regard to meningitis, with partial regression of the cerebellar abscess. Follow-up lumbar punctures were sterile, and the patient’s neurological condition stabilized, allowing avoidance of neurosurgical drainage. Conclusions: Meningitis and brain abscess caused by MDRA. baumannii represent rare clinical entities with potentially severe outcomes. Intrathecal administration of colistin, in combination with systemic multidrug therapy, proved decisive in controlling the infection. An interdisciplinary approach and individualized antimicrobial regimens are essential to achieving a favorable prognosis in such complex cases. Full article

Laboratory confirmation of invasive meningococcal disease (IMD) relies on detection of Neisseria meningitidis in a biological specimen. Clinical management guidelines for patients presenting with signs and/or symptoms of meningitis and encephalitis emphasize the need for appropriate specimen collection for laboratory testing. To explore the potential for IMD under-diagnosis, we reviewed medical records of patients admitted with signs and/or symptoms of meningitis or encephalitis at five hospitals in Louisville, Kentucky, in 2014 to 2023. Among 675 patients admitted with meningitis and/or encephalitis with cerebrospinal fluid (CSF) cultures who received antibiotics, 300 (44.4%) received antibiotics before CSF collection. Among 431 with blood cultures who received antibiotics, 133 (30.9%) received antibiotics before blood collection. Among 751 patients with CSF collected, 651 (86.7%) CSF specimens were tested using polymerase chain reaction (PCR) for N. meningitidis detection. No blood specimens were PCR-tested. These findings indicated that current standard-of-care practices may lead to IMD under-diagnosis. Since public health surveillance relies on IMD laboratory diagnosis, these findings highlight the potential for under-ascertained IMD by surveillance. Full article

Healthcare professionals (HCPs) working in paediatric settings are routinely exposed to respiratory pathogens, increasing their risk of asymptomatic colonisation by meningitis-associated bacteria. This study is the first to assess oropharyngeal and nasopharyngeal carriage of major bacterial meningitis pathogens among paediatric HCPs in Benin, and to identify associated risk factors. A cross-sectional analytical study was conducted in nine hospitals between 1 September 2023 and 30 September 2024. Data collection involved a structured questionnaire and paired oropharyngeal and nasopharyngeal swabs. Culture-based identification and antimicrobial susceptibility testing were performed according to CA-SFM guidelines. By culture method, Streptococcus pneumoniae was the most frequently isolated pathogen, mainly from oropharyngeal samples (47.5%). Most of these strains exhibited multidrug resistance. In nasopharyngeal samples analysed by real-time PCR, detection rates for S. pneumoniae were markedly higher (24.4%) compared to culture (5.0%), highlighting the limited sensitivity of conventional methods in detecting asymptomatic carriage. Pneumococcal colonisation was significantly associated with recent respiratory tract infections, and residence in high-risk areas (p < 0.05). These findings underscore the need for enhanced molecular surveillance, along with strengthened infection control measures and targeted vaccination strategies, to mitigate the risk of horizontal transmission in paediatric wards. Full article

Bacterial meningitis is one of the most serious infections. Salmonella meningitis is associated with a high prevalence of long-term adverse outcomes, often linked to acute complications and a broad range of potential neurological sequelae following the infection. Acute complications such as brain abscesses and chronic complications such as hearing loss and developmental delay. In this report, we present a case of a 2-month-old male patient with seizures, hypoactivity and respiratory symptoms, who was found to have Salmonella bacteremia complicated by Salmonella and Human Herpes Virus-6 (HHV-6) meningitis, as well as rhinovirus bronchiolitis, along with follow-up findings. The patient’s data, including demographics, presenting symptoms, physical examination findings, and whole exome sequence results, as well as investigations such as complete blood count (CBC), cerebrospinal fluid (CSF) analysis, liver enzyme levels, and imaging findings, were collected from the electronic medical record system using a case report form. In addition, immunological workups were performed, as serious Salmonella infections were more common in immunocompromised patients. In the literature, there was no clear correlation between Salmonella and HHV-6 meningitis, rhinovirus bronchiolitis, and the complications that developed in this infant. This case report provides valuable insights into the clinical spectrum and long-term outcomes of patients with Salmonella meningitis. Full article

Meningococcal meningitis is a deadly acute bacterial infection caused by the Neisseria meningitidis bacterium that affects the membrane covering the brain and spinal cord. The World Health Organization launched the “Defeating bacterial meningitis by 2030” initiative in 2018, which relies on recent discoveries of cheap and effective vaccines. Here, we consider one important factor—human behavior—which is often neglected by immunization campaigns. We constructed a game-theoretic model of meningitis in the meningitis belt, where individuals make selfish rational decisions whether to vaccinate based on the assumed costs and the vaccination decisions of the entire population. We identified conditions when individuals should vaccinate, and we found the optimal (equilibrium) population vaccination rate. We conclude that voluntary compliance significantly reduces the endemic levels of meningitis if the cost of vaccination relative to the cost of the disease is sufficiently low, but it does not eliminate the disease. We also performed uncertainty and sensitivity analysis on our model. Full article

An outbreak characterized by clinical signs of diarrhea and paralysis, occasionally progressing to fatal outcomes, occurred at an ostrich breeding facility. Conventional antibiotic treatments proved ineffective. To investigate the etiology of the disease, brain and liver specimens were collected for diagnostic analysis. An Escherichia coli (E. coli) isolate, designated strain HZDC01, was obtained from cerebral tissues, and whole-genome sequencing was performed for genomic characterization. Genomic analysis revealed that the chromosomal DNA harbors numerous resistance genes, conferring multidrug resistance through complex mechanisms. Furthermore, a p0111-type plasmid carrying the bla_CTX-M-55 gene and an IncX1-type plasmid harboring rmtB, sul1, APH(6)-Id, tet(A), AAC(3)-IIc, aadA2, bla_TEM-1B, and floR genes were identified. These plasmids carry numerous mobile genetic elements that can disseminate via horizontal gene transfer, thereby amplifying the risk of resistance-gene spread within bacterial populations. Additionally, the ibeB and ibeC genes, which encode proteins involved in the invasion of brain microvascular endothelial cells, were identified. These genes may facilitate E. coli penetration of the blood–brain barrier, potentially leading to meningitis and posing a life-threatening risk to the host. This is the first report of the isolation and characterization of extended-spectrum beta-lactamase E. coli from the brain of an ostrich with paralysis. The findings provide valuable genomic insights into the antimicrobial resistance profiles and pathogenic mechanisms of ostrich-derived E. coli isolates. Full article