Medical Microbiology and Immunology最新文献

{"title":"Identification of mitochondrial metabolism-associated tuberculosis key genes and construction of a diagnostic model based on WGCNA.","authors":"Qiaoqiao Wu, Qiongna Zheng, Chemin Wu","doi":"10.1007/s00430-026-00894-y","DOIUrl":"https://doi.org/10.1007/s00430-026-00894-y","url":null,"abstract":"<p><p>Despite recent advances, tuberculosis (TB) remains a complex global health challenge, with its causative bacterium, Mtb, actively manipulating host cellular metabolism to survive. Therefore, studying mitochondrial metabolism-related genes is crucial, as they offer a promising avenue for identifying diagnostic biomarkers and developing new host-directed therapies to combat the disease. This study integrated transcriptomic datasets from three TB cohorts in the Gene Expression Omnibus (GEO) database (training set: GSE83456; validation sets: GSE42826 and GSE19444). Differential analysis was performed using the \"limma\" package (with |logFC| > 1 and adjusted p-value < 0.05) to identify mitochondrial metabolism-related differentially expressed genes. Diagnostic biomarkers were determined by combining weighted gene co-expression network analysis (WGCNA), and the effectiveness of the model was evaluated using receiver operating characteristic (ROC) curve analysis. Immune infiltration characteristics were assessed via single-sample gene set enrichment analysis (ssGSEA) and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), pathway enrichment analysis was conducted through GSEA, molecular subtypes were classified using the non-negative matrix factorization (NMF) algorithm, and MicroRNA (miRNA) and transcription factor (TF) regulatory networks were predicted using \"miRNet\" and \"NetworkAnalyst\". We identified 3 mitochondrial metabolism-related biomarkers (TYMP, SCO2, GK) with remarkable diagnostic performance (area under the curve [AUC] = 0.973 across cohorts). These genes were closely associated with altered immune infiltration patterns, characterized by enhanced inflammatory responses in macrophages and monocytes, along with a reduction in T-cell subsets. These genes are associated with ribosome and innate immune pathways. Furthermore, tuberculosis patients were stratified into two distinct molecular subtypes exhibiting specific immune microenvironment features. Regulatory network analysis revealed hsa-miR-10b-5p and transcription factor hubs (SP3/SP1) as potential master regulators. This study identifies a mitochondrial metabolism-based gene signature for TB diagnosis, revealing novel host-pathogen mechanisms and enabling potential targeted therapies for precision medicine.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular pathogen manipulation of ER-phagy: direct receptor targeting and indirect pathway perturbation.","authors":"Xiaoqi Lu, Yang Yang, Ranhui Li, Yating Wen","doi":"10.1007/s00430-026-00891-1","DOIUrl":"10.1007/s00430-026-00891-1","url":null,"abstract":"<p><p>Selective autophagy of the endoplasmic reticulum (ER-phagy) maintains intracellular homeostasis by selectively removing damaged ER membranes and contained misfolded proteins. This review delineates the core molecular mechanisms of canonical autophagy, then systematically describes three types of ER-phagy (macro-ER-phagy, micro-ER-phagy, and vesicular ER-phagy), their signature receptors, subdomain specificities, and regulatory mechanisms, alongside a comparative analysis of the evolutionary divergence between yeast and mammalian ER-phagy receptor systems. At the direct regulation level, diverse intracellular pathogen strategies targeting ER-phagy receptors are examined, including proteasomal degradation and spatial sequestration of FAM134B by viruses, non-canonical micro-ER-phagy hijacking by retroviruses, constitutive antiviral defense mediated by FAM134B against Ebola virus, and bidirectional modulation of this receptor by bacterial effectors and pathogen-associated molecular patterns. At the indirect regulation level, intracellular pathogen-mediated perturbation of upstream nodes-including the UPR, ERAD, ER-RQC/UFMylation, and core macroautophagy machinery-is summarized. These findings underscore the dual role of ER-phagy as both a host defense barrier and a target for pathogen exploitation, providing novel insights into intracellular pathogenic mechanism.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-γ-response to mycobacterial glycopeptidolipids in patients with pulmonary non-tuberculous mycobacterial infection.","authors":"Mathis Steindor, Sophia Dachmann, Florian Stehling, Margarete Olivier, Jan Kehrmann, Peter A Horn, Raquel Villar-Hernández, Svenja Straßburg, Matthias Welsner, Sivagurunathan Sutharsan, Monika Lindemann","doi":"10.1007/s00430-026-00892-0","DOIUrl":"10.1007/s00430-026-00892-0","url":null,"abstract":"<p><p>The understanding of host responses to pulmonary infection with non-tuberculous mycobacteria (NTM) is incomplete and immunodiagnostic tools are not established. Unlike mycobacteria of the Mycobacterium tuberculosis complex, several NTM express glycopeptidolipids (GPLs) in their cell wall. Here, we investigate the interferon-γ response to mycobacterial GPLs and its diagnostic use in patients with pulmonary NTM infection. M. avium-derived GPLs were used for in vitro stimulation of peripheral blood mononuclear cells in an ELISpot assay of patients with pulmonary NTM infection and 3 control groups, (1) patients with tuberculosis (TB), (2) patients with cystic fibrosis without evidence of NTM infection (CF) and (3) healthy controls (HC). Immune responses were compared between the groups and for the subgroup of NTM patients with either M. avium complex (MAC) or M. abscessus complex (MABC). Interferon-γ responses of 31 patients with NTM (16 MABC, 11 MAC, 1 MABC & MAC, and 3 other NTM) were compared to 43 controls (15 TB, 15 CF, 13 HC). Responses to GPLs were significantly stronger in the NTM group compared to controls (13.5 vs. 1.5 spots per 300,000 PBMC, p < 0.0001, data represent median values). MAC patients had an overall stronger reaction than MABC patients. Assay sensitivity and specificity were 64 and 98% for MAC, 19 and 95% for MABC, and 32 and 98% for all NTM, respectively. Mycobacterial GPLs are potent drivers of interferon-γ-responses. Patients with pulmonary NTM infection show stronger immune responses to GPLs compared to uninfected participants, making GPLs a promising target for the development of NTM immune diagnostic tools.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPAR-γ participates in macrophage polarization induced by Pentatrichomonas hominis.","authors":"Yu Zheng, Tao-Tao Yue, Xi-Chen Zhang, Jian-Hua Li, Peng-Tao Gong, Xiao-Cen Wang, Xin Li, Xu Zhang, Nan Zhang","doi":"10.1007/s00430-026-00889-9","DOIUrl":"10.1007/s00430-026-00889-9","url":null,"abstract":"<p><p>Pentatrichomonas hominis (P. hominis), a protozoan inhabiting the cecum and colon of humans and vertebrates, is associated with diarrhea. The innate immunity plays a crucial role in defending against parasitic infections. Among these, macrophages are involved in immune evasion, immune surveillance, and tissue repair. Parasites alter the host's immune homeostasis by modulating macrophage polarization. However, the regulation of macrophage polarization by P. hominis remains unreported. Herein, we found that co-incubation of peritoneal macrophages with P. hominis for 6 h increased CD11c expression, IL-6 and IL-12 levels, and NF-κB p65 phosphorylation. After 24 h of co-culture, CD206 and PPAR-γ expression, as well as IL-4 and IL-10 levels, were elevated in peritoneal macrophages. PPAR-γ agonist GW1929 increased expression of CD206, PPAR-γ, IL-4, and IL-10 in peritoneal macrophages and cecal tissue induced by P. hominis, whereas PPAR-γ antagonist GW9662 had the opposite effect. In mice, GW1929 was validated to alleviate inflammation and injury, whereas GW9662 exacerbated them. Taken together, this study first unveiled that P. hominis modulates macrophage polarization in vitro and that PPAR-γ is associated with this process. GW1929 treatment alleviates inflammation and pathological damage caused by P. hominis infection. These findings provide insights and evidence for further investigation into the innate immune response against P. hominis infection in the host.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pneumococcal vaccine serotype-specific antibody levels among PCV-unvaccinated children in Karnataka, India.","authors":"Shincy M Ramakrishnan, R H Ranjith, Akhila M Mavuppadi, Honnamachanahalli T Yashoda, Geetha Nagaraj, Vani Rajashekaraiah, K L Ravikumar","doi":"10.1007/s00430-026-00890-2","DOIUrl":"10.1007/s00430-026-00890-2","url":null,"abstract":"<p><p>The immunogenicity of pneumococcal vaccines is commonly assessed using post-vaccination serotype-specific IgG antibody concentrations. Therefore, characterization of baseline antibody levels in vaccine-naïve populations is essential for understanding naturally acquired immunity and accurately interpreting vaccine responses. However, data on baseline serotype-specific IgG levels in healthy, unvaccinated Indian children remain limited. This study aimed to measure baseline serotype-specific pneumococcal IgG antibody levels in healthy vaccine-naïve Indian children. Baseline serotype-specific IgG antibody concentrations against 24 pneumococcal vaccine serotypes were measured in 600 healthy PCV-unvaccinated Indian children aged ≤ 5 years using the WHO-recommended ELISA method. Geometric mean concentrations (GMCs) were calculated for each pneumococcal serotype, and variations in antibody levels were analyzed according to age, gender, and season. Baseline IgG GMCs varied widely across serotypes, ranging from 0.14 µg/mL for serotype 12 F to 5.65 µg/mL for serotype 14. Overall, 71% of serotypes exhibited GMCs above the proposed protective threshold of 0.35 µg/mL. Age-dependent increases in antibody concentrations were observed, with peak GMCs in children aged > 36-≤48 months. Gender-based differences were minimal, with significantly higher GMCs observed in females only for serotype 9 N, whereas seasonal variation was evident for selected serotypes. Healthy Indian children demonstrate considerable heterogeneity in baseline serotype-specific pneumococcal IgG levels prior to vaccination. These findings provide important baseline immunological data on serotype-specific pneumococcal IgG levels in healthy, PCV unvaccinated Indian children and may serve as a useful reference for interpreting future pneumococcal vaccine immunogenicity studies and seroepidemiological investigations.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel conserved B-cell epitope in the glycoprotein of rabies virus.","authors":"Yumei Chen, Xiaohui Zhang, Yanhua Qi, Hongliang Liu, Enping Liu, Xifang Zhu, Jingming Zhou, Chao Liang, Sixuan Wu, Aiping Wang","doi":"10.1007/s00430-026-00887-x","DOIUrl":"10.1007/s00430-026-00887-x","url":null,"abstract":"<p><p>Rabies virus (RABV), a single-stranded RNA virus, invades the central nervous system and causes acute, zoonotic diseases worldwide. The glycoprotein (G) of RABV is the only surface antigen responsible for inducing potent neutralizing antibodies, making it a key target for medical countermeasures. In this study, two anti-G protein monoclonal antibodies (mAbs) were prepared using hybridoma cell technology, with their high specificity and robust reactivity validated by indirect enzyme-linked immunosorbent assay (i-ELISA), indirect immunofluorescence assay (IFA) and Western blot. Through systematic epitope mapping using a series of truncated G protein fragments, two mAbs (1G2 and 4E5) were found to recognize a minimal linear epitope, AEDFVEVHLP (amino acids 412-421) through Dot-ELISA and i-ELISA. Alanine-scanning mutagenesis further defined the core binding residues within this epitope as ⁴¹²Ala-Glu-Asp-Phe-Val⁴¹⁶, ⁴¹⁸Val, ⁴²⁰Leu, and ⁴²¹Pro. Bioinformatic analysis with MEGA software revealed highly conserved with conservative substitutions of this epitope across diverse RABV of genotype 1. Homology modeling with SWISS-MODEL localized the epitope \"⁴¹²AEDFVEVHLP⁴²¹\" to a solvent-exposed α-helical conformation on the G protein surface. And this epitope is located in the extracellular C-terminal region, Prior studies have demonstrated that this region plays a role in stabilizing the trimerization of the rabies virus glycoprotein (RVG). In conclusion, our study identifies a novel, highly conserved with conservative substitutions linear B-cell epitope on the RABV glycoprotein, providing a precise molecular target for the rational design of next-generation epitope-based vaccines and specific diagnostic tools.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epstein-Barr virus serological profiles and atypical patterns in a large tertiary-care cohort: a retrospective study of 11,503 patients.","authors":"Sevim Gayenur Buyukberber, Esra Sert, Alparslan Toyran, Bedia Dinc","doi":"10.1007/s00430-026-00888-w","DOIUrl":"10.1007/s00430-026-00888-w","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection is highly prevalent worldwide, and its seroepidemiology varies according to age and sociodemographic factors. Recent observations suggest potential shifts in exposure dynamics following the COVID-19 pandemic and ongoing challenges in interpreting atypical antibody profiles. This retrospective study evaluated EBV serological patterns in 11,503 patients tested VCA IgM, VCA IgG, EA IgG, and EBNA IgG between January 2023 and August 2025 at a tertiary-care hospital. Patterns were classified as seronegative, primary infection, past infection, reactivation pattern, or atypical. Age- and sex-related distributions were analyzed using logistic regression. Past infection was the most frequent profile (64.0%), followed by seronegativity (19.8%) and atypical patterns (14.3%). VCA IgG seropositivity reached 53.2% in the 5-9 age group and increased with age. Age was strongly associated with EBV seropositivity, and female sex independently increased the odds of VCA IgG positivity. Atypical serological patterns were more common in younger individuals and showed an inverse association with age, while sex had no independent effect. Isolated VCA IgG positivity was the most common atypical pattern. These findings provide updated data on EBV serological patterns in a large tertiary-care cohort during the post-pandemic period. The observed age-specific seropositivity rates may suggest a trend toward later EBV exposure; however, the absence of a direct pre-pandemic comparator requires cautious interpretation. Accurate interpretation of atypical EBV serological profiles remains important in clinical practice and should consider patient age, timing of antibody responses, and analytical characteristics of the assay.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell profiling reveals IFI44L as a central regulator of immune dysregulation in high HIV viral load.","authors":"Jiamin Gao, Yanjun Li, Jinping Huang, Xianzhen Huang, Qingdong Zhu, Cailing Wei, Jieling Chen, Shunda Luo, Zhouhua Xie","doi":"10.1007/s00430-026-00884-0","DOIUrl":"https://doi.org/10.1007/s00430-026-00884-0","url":null,"abstract":"<p><p>Human Immunodeficiency Virus (HIV) infection impairs the immune system, diminishing its ability to defend against pathogens and increasing susceptibility to infections and diseases. To gain a comprehensive understanding of the heterogeneity, functions, and regulatory mechanisms of immune cells affected by different HIV viral loads, we investigated the biological impacts of HIV infection on the human body. We reanalyzed a publicly available peripheral blood mononuclear cell (PBMC) single-cell RNA sequencing dataset (GSE157829) comprising three people living with HIV with high viral load (HL-HIV), three people living with HIV with low viral load (LL-HIV), and one healthy control donor. We constructed single-cell immune atlases that represent different viral load profiles. We also analyzed the dynamic changes in specific immune cell subpopulations to gain insights into their signaling pathways, developmental trajectories, and key transcriptional regulators. At the single-cell level, non-classical monocyte subpopulations, specifically ncMono_LYN_TCF7L2 and ncMono_IL32, functioned as immunosurveillance elements but also activated pro-inflammatory pathways, leading to immune activation. B_CD83 subpopulation was critical in B cell development, facilitating B cell differentiation and tolerance. Naive.T_TNFAIP3 subpopulation exhibited anti-inflammatory effects and protected against aberrant apoptosis. Central memory T (TCM)_TCF7_CCR7 subpopulation played a crucial role in regulating the expansion of HIV-specific CD8⁺ T cells and maintaining the immune response. Additionally, we observed a significant enrichment of IFI44L-positive subpopulations across different cell types, particularly in HL-HIV samples. Our findings demonstrate that HIV infection increases the complexity of immune cell subpopulations. Notably, IFI44L has emerged as a potential disease hub gene in HL-HIV samples, highlighting its potential as a novel biomarker for HIV.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics and characterization of extracellular vesicle release from cells infected with a clinical isolate of respiratory syncytial virus A (ON1 genotype).","authors":"Matteo Fracella, Valeria Manganelli, Alessandra Pierangeli, Carolina Scagnolari, Manuel Pacchiele, Eleonora Coratti, Roberta Campagna, Gloria Riitano, Federica Fratini, Agostina Longo, Maurizio Sorice, Guido Antonelli","doi":"10.1007/s00430-026-00886-y","DOIUrl":"https://doi.org/10.1007/s00430-026-00886-y","url":null,"abstract":"<p><p>Despite the recent approval of preventive measures, the disease burden of respiratory syncytial virus (RSV) infection in children and older adults remains significant. To improve understanding of RSV disease, this study characterized extracellular microvesicles (EMVs) secreted during in vitro infection with a clinical RSV-A (ON1 genotype) strain (RSV/40G-A), isolated in 2022 from a pediatric pneumonia case. The type and content of EMVs released by A549 and BEAS-2B respiratory epithelial cells infected with this clinical isolate were analyzed up to 96 h post-infection (hpi). RSV infection induced a time-dependent increase in EMV levels compared to uninfected controls. EMVs released by infected BEAS-2B and A549 cells contained increasing levels of RSV nucleocapsid protein (RSV-NP) and viral RNA with a peak at 72 hpi. These findings suggest that the kinetics of vesicular release and EMV content are modulated during RSV infection. EMV secretion by host cells may constitute a potential mechanism for intercellular communication or immune activation.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Granulomatous amoebic encephalitis: pathogenesis, diagnostic advances, therapeutic challenges, and emerging treatment strategies.","authors":"Megha Gautham, Poluri Koteswari","doi":"10.1007/s00430-026-00885-z","DOIUrl":"10.1007/s00430-026-00885-z","url":null,"abstract":"<p><p>Granulomatous amoebic encephalitis (GAE) is a rare but highly fatal central nervous system infection caused primarily by Acanthamoeba spp. and Balamuthia mandrillaris. Delayed diagnosis and the absence of standardized treatment protocols contribute to mortality exceeding 90%. This review summarizes current knowledge regarding GAE pathogenesis, diagnosis, therapeutic challenges, and emerging treatment strategies. The pathogenesis involves amoebic adhesion, secretion of proteases and phospholipases, host inflammatory responses, and blood-brain barrier disruption. Recent advances in molecular diagnostics improve early pathogen detection, while drug repurposing, nanotechnology-based delivery systems, and cyst-targeted approaches represent promising therapeutic strategies. Nevertheless, treatment remains challenging because of poor blood-brain barrier penetration, cyst-associated resistance, and limited clinical evidence. Continued integration of molecular diagnostics, mechanistic studies, translational research, and multicentre clinical investigations is essential for improving outcomes in this devastating disease.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}