Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Pathogen spectrum and triple-criteria interpretation algorithm of BALF-targeted NGS in children with refractory severe community-acquired pneumonia in mountainous Northeastern Sichuan: a single-center retrospective study.","authors":"Rongjie Chen, Zhe Xu, Tingting He, Xiao Liu, Yi Ding, Xin Hou","doi":"10.3389/fcimb.2026.1929990","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1929990","url":null,"abstract":"<p><strong>Background: </strong>Severe community-acquired pneumonia (SCAP) causes substantial pediatric hospitalization and respiratory failure in mountainous western China. Conventional microbial assays show limited sensitivity for fastidious pathogens and mixed infections. Targeted next-generation sequencing (tNGS) using bronchoalveolar lavage fluid (BALF) enables broad-spectrum pathogen detection at lower cost than whole-metagenomic sequencing. However, many previous tNGS studies directly equate multiple microbial nucleic-acid signals with true coinfection, which may lead to unnecessary combined anti-infective therapy.</p><p><strong>Methods: </strong>This single-center retrospective study enrolled 86 children aged < 14 years with refractory SCAP who underwent BALF-tNGS testing at Guangyuan Central Hospital between March 2023 and September 2024. We developed a triple-criteria interpretive algorithm combining an exploratory empirical pathogen-load cut-off (>1.0 × 10⁶ copies/mL), inflammatory biomarkers (CRP, PCT), and chest imaging to discriminate genuine active coinfection from airway colonization. This load threshold was empirical and not internally validated by ROC analysis in our dataset. Patients were stratified into four age subgroups; diagnostic concordance was assessed among 34 patients with parallel routine microbial tests.</p><p><strong>Results: </strong>In total, 229 pathogen isolates were identified. Viruses predominated (58.9%, 135/229), followed by bacteria (32.8%, 75/229). The three most frequent pathogens were Haemophilus influenzae (32.56%), Streptococcus pneumoniae (30.23%), and respiratory syncytial virus A (RSV-A, 18.60%). While 82.6% (71/86) of patients harbored ≥2 pathogen nucleic-acid signals, only 17.4% (15/86) fulfilled criteria for clinical coinfection, dominated by virus-bacterial dual infection. Viral detection rates tended to decline with increasing age, whereas bacterial positivity was higher among preschool- and school-age children. A prominent spring epidemic peak was observed during May-June 2023. Only 22.86% of paired routine microbial tests showed full concordance with tNGS. These single-center data cannot be generalized to all pediatric severe-pneumonia populations. Most abundant multi-pathogen tNGS signals represented colonization or residual dead-microbe nucleic acid instead of true active infection.</p><p><strong>Conclusion: </strong>Our triple-criteria interpretive framework offers standardized rules for grassroots mountain hospitals to reduce over-prescription of combined antibiotics and antivirals when interpreting BALF-tNGS results for children with refractory SCAP.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1929990"},"PeriodicalIF":5.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Candida albicans</i> subverts host programmed cell death: a unified framework from pyroptosis to ferroptosis.","authors":"Limin Fan, Ruining Huang, Kexin Wang, Manting Ni, Xiuyu Nong, Zhenmou Xie, Bo Fu, Lijun Mo, Yinyuan Lan, Qingqing Xu, Wenhan Cao, Xinyue Li, Xueting Liu, Yaohua Xue","doi":"10.3389/fcimb.2026.1960578","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1960578","url":null,"abstract":"<p><p><i>Candida albicans</i> is a major opportunistic fungal pathogen that causes substantial morbidity and mortality, particularly in immunocompromised individuals. Increasing evidence indicates that its pathogenicity extends beyond classical virulence traits and involves active engagement of host programmed cell death (PCD) pathways. In this review, we propose a unified mechanistic framework to explain how <i>C. albicans</i> virulence programs-including hyphal morphogenesis, candidalysin-mediated epithelial injury, cell wall remodeling, and metabolic adaptation-interact with host sensing systems to shape distinct yet interconnected forms of cell death. Among the currently implicated pathways, pyroptosis is the most strongly supported and represents the clearest link between fungal invasion, inflammasome activation, and inflammatory tissue injury. By contrast, apoptosis appears to be more heterogeneous and context-dependent, whereas necroptosis and ferroptosis remain emerging mechanisms whose contributions likely vary across cell types, tissues, and stages of infection. We further examine how host compartments, including epithelial cells, macrophages, neutrophils, and IL-17-associated immune circuits, amplify, buffer, or redirect these death responses, thereby influencing the balance between fungal clearance and immunopathology. Particular emphasis is placed on tissue specificity, as the biological consequences of PCD differ markedly across oral, vaginal, intestinal, hepatic, and disseminated candidiasis. Finally, we discuss the translational implications of this framework for host-directed antifungal strategies and argue that therapeutic modulation of cell death will require careful attention to timing, tissue context, and preservation of protective immunity. This review provides an evidence-weighted and integrative perspective on how <i>C. albicans</i> subverts host cell death and how these processes may be leveraged for future therapeutic innovation.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1960578"},"PeriodicalIF":5.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A RIPK2-associated macrophage program links mycobacterial sensing to osteoclastogenesis in bone tuberculosis.","authors":"Yuyang Zhang, Ziyang Zhang, Dongyang Zhang, Jiulin Tan, Zhaoxin Ma, Qingyang Xiao, Jie Zhang, Qixiu Yu, Zehua Zhang, Yong Tang, Ce Dou, Fei Luo","doi":"10.3389/fcimb.2026.1970405","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1970405","url":null,"abstract":"<p><strong>Introduction: </strong>In bone tuberculosis, Mycobacterium tuberculosis (Mtb) infection triggers inflammatory bone destruction, but the macrophage programs that convert Mtb signals into osteoclastogenesis remain poorly defined.</p><p><strong>Methods: </strong>We generated single-cell RNA-seq data from human spinal tuberculosis lesions and integrated them with public H3K27ac ChIP-seq, RNA-seq, Hi-C, and motif data. Key findings were validated in primary macrophages stimulated with Mtb lysate.</p><p><strong>Results: </strong>We identified 64 Mtb-induced super-enhancers, and integrated analysis prioritized RIPK2 as a candidate. Lesion-associated myeloid populations showed enhanced inflammatory and osteoclast-priming signatures, followed a mononuclear phagocyte-to-osteoclast trajectory, and exhibited a linear correlation between RIPK2 expression and osteoclast score. In mice, RIPK2 localized to CTSK-positive bone interfaces. <i>In vitro</i>, Mtb stimulation induced <i>Il1b, Nfkbiz</i>, and <i>Tnfrsf11a</i> expression, IL-1β secretion, and surface RANK upregulation; these responses were suppressed by the RIPK2 inhibitor GSK583.</p><p><strong>Discussion: </strong>These findings link RIPK2 to both macrophage inflammatory signaling and osteoclastogenesis in bone tuberculosis, suggesting that RIPK2 may be a target for limiting infection-driven bone destruction.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1970405"},"PeriodicalIF":5.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diethyl fumarate exhibits potent activity against differentially culturable <i>Mycobacterium tuberculosis</i> persisters.","authors":"Amelie J Herbert, Obolbek Turapov, Fraser MacDonald, Irawaty Djaharuddin, Muhammad Nasrum Massi, Douglas B Kell, Vadim A Makarov, Galina V Mukamolova","doi":"10.3389/fcimb.2026.1901638","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1901638","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (Mtb), remains the leading cause of death from a single infectious agent. During infection, Mtb forms drug-tolerant persisters, including differentially culturable (DC) cells that fail to grow on solid media and contribute to prolonged TB treatment and disease relapse. DC Mtb formation is driven by host inflammatory responses, particularly nitric oxide (NO), suggesting that anti-inflammatory agents may limit persister generation. Here, we developed a workflow to evaluate the activity of drug candidates against DC Mtb persisters. This approach was validated using dimethyl fumarate (DMF) derivatives, as DMF has previously been shown to eradicate DC Mtb but is limited by instability and poor solubility. We assessed DMF and nine DMF derivatives for antimycobacterial activity. The workflow included antimicrobial susceptibility testing against <i>Mycobacterium tuberculosis</i> (Mtb) and <i>Mycobacterium abscessus</i> (Mabs), followed by cytotoxicity evaluation and measurement of NO release in lipopolysaccharide (LPS)-stimulated macrophages. Selected DMF derivatives were further tested against DC Mtb persisters generated <i>in vitro</i> using a NO donor as well as persisters recovered from interferon γ-stimulated macrophages. DMF and diethyl fumarate (DEF) inhibited Mtb growth, while ethyl-3-benzoylacrylate (EBL) and methyl-trans-4-oxo-2-pentenoate (MTOP) exhibited bactericidal activity against both Mtb and Mabs. DEF effectively eliminated DC Mtb in infected macrophages, with activity comparable to DMF. This anti-DC Mtb persister effect was associated with reduced NO production, highlighting the importance of anti-inflammatory activity in targeting DC Mtb persisters. DMF and its more soluble and stable derivative DEF represent promising candidates for the development of therapies targeting DC Mtb persisters. Their dual anti-inflammatory and anti-mycobacterial properties support their potential as a novel therapeutic strategy against persistent tuberculosis infections.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1901638"},"PeriodicalIF":5.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leishmaniasis and vaccine development: current progress, challenges, and future perspectives.","authors":"Somaditya Dey, Anushka Ghosh, Debarati Mukherjee","doi":"10.3389/fcimb.2026.1929424","DOIUrl":"https://doi.org/10.3389/fcimb.2026.1929424","url":null,"abstract":"<p><p>Leishmaniasis remains one of the most important neglected tropical diseases (NTDs), affecting millions of individuals across tropical and subtropical regions. Caused by protozoan parasites of the genus <i>Leishmania</i> and transmitted by infected female phlebotomine sandflies, the disease manifests in a spectrum of clinical forms ranging from localized cutaneous lesions to fatal visceral infections. Despite substantial progress in disease control programmes, leishmaniasis continues to pose significant public health, socioeconomic, and healthcare challenges in endemic countries. Current chemotherapeutic options, including pentavalent antimonials, amphotericin B formulations, miltefosine, paromomycin, and pentamidine, are constrained by toxicity, prolonged treatment regimens, high costs, and the emergence of drug-resistant parasite strains. Moreover, the absence of a licensed human vaccine remains a major obstacle to sustainable disease control. Consequently, the development of effective vaccines has emerged as a major research priority. Advances in molecular parasitology, immunology, and vaccine technology have led to the development of first-generation killed and live-attenuated vaccines, second-generation recombinant protein and subunit vaccines, and third-generation nucleic acid-based vaccine platforms. Recent innovations involving mRNA vaccines, viral vectors, genetically attenuated parasites, and controlled human infection models have further accelerated translational research. In parallel, advances in genomics, immunoinformatics, artificial intelligence, and nanotechnology are facilitating the identification of novel therapeutic targets, vaccine antigens, and precision intervention strategies. Nevertheless, the complex biology of <i>Leishmania</i>, antigenic diversity, and sophisticated immune-evasion mechanisms continue to impede vaccine licensure. This review discusses the global burden of leishmaniasis, host-parasite interactions, current therapeutic approaches, mechanisms of drug resistance, vaccine development strategies, and emerging technologies that are shaping the future of leishmaniasis prevention and treatment.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1929424"},"PeriodicalIF":5.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of gut microbiota in paediatric short bowel syndrome.","authors":"Cheng Zeng, Lidan Liang, Tingfang Lv","doi":"10.3389/fcimb.2026.1970119","DOIUrl":"10.3389/fcimb.2026.1970119","url":null,"abstract":"<p><p>Short bowel syndrome (SBS) is one of the leading causes of intestinal failure in children. Its development is influenced not only by the length and function of the residual intestine but is also closely related to the homeostasis of the gut microbiota. In recent years, the role of the gut microbiota in intestinal adaptation, metabolic regulation, and the development of complications in pediatric SBS has gradually garnered attention. This review summarizes the characteristics of the gut microbiota, mechanisms underlying dysbiosis, associations with complications, and microbiota-targeted therapeutic strategies in pediatric SBS. Existing studies indicate that children with SBS exhibit reduced microbiota diversity, compositional abnormalities, and metabolic dysfunction. Gut microbiota dysbiosis may be associated with intestinal barrier disruption, immune dysregulation, alterations in residual intestinal structure, and parenteral nutrition, and may contribute to the development and progression of complications such as small intestinal bacterial overgrowth (SIBO), D-lactic acidosis (D-LA), and liver injury. Strategies such as probiotics, nutritional modulation, and fecal microbiota transplantation (FMT) have shown potential clinical value, although their efficacy and safety require further validation. Future studies integrating multi-omics approaches and long-term longitudinal investigations are needed to elucidate the mechanisms underlying interactions between the microbiota and host, thereby providing a theoretical basis for microbiota-targeted interventions and improving long-term outcomes in children with SBS.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1970119"},"PeriodicalIF":5.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13684125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of a tetravalent dengue vaccine incorporating T-cell epitopes from NS3 and NS5 proteins and B-cell epitopes from the envelope protein using an immunoinformatics approach.","authors":"Theerawat Dobutr, Pemikar Srifa, Nawamin Pinpathomrat","doi":"10.3389/fcimb.2026.1934834","DOIUrl":"10.3389/fcimb.2026.1934834","url":null,"abstract":"<p><p>Dengue virus remains a major global health threat due to its four antigenically diverse serotypes and limited treatment and vaccine options. This study aimed to design and evaluate a rational tetravalent multi-epitope vaccine capable of eliciting broad cross-serotype immune responses against dengue virus. An immunoinformatics-driven strategy was employed to identify CTL, HTL, and B-cell epitopes from the NS3, NS5, and envelope domain III proteins of DENV-1 to DENV-4 based on antigenicity, allergenicity, and predicted immunogenic potential, followed by assessment of HLA population coverage. Among the selected CTL epitopes, three were completely conserved across all four serotypes, while one HTL epitope showed the highest conservation among the selected MHC class II epitopes. High-scoring linear B-cell epitopes were identified across EDIII of all four DENV serotypes, with several closely matching experimentally validated epitopes and predominantly localizing to the FG loop and DIII-DI hinge regions. The combined MHC class I and II population coverage reached 98.05% worldwide. The final vaccine construct comprised 584 amino acids incorporating 11 CTL, 14 HTL, and 7 B-cell epitopes linked to an N-terminal β-defensin adjuvant. Molecular docking, MM/GBSA calculations, and 200 ns molecular dynamics simulations demonstrated stable interactions with both TLR2 and TLR4/MD2 complexes, with docking binding energies of -16.2 and -26.0 kcal/mol and MM/GBSA binding free energies of -27.15 ± 0.54 and -52.50 ± 0.55 kcal/mol, respectively. <i>In silico</i> immune simulation predicted substantial lymphocyte activation, enhanced IFN-γ secretion, predicted antigen clearance, and immunoglobulin class switching. Collectively, the proposed tetravalent multi-epitope vaccine was predicted to provide broad cross-serotype epitope representation, substantial population coverage, and favorable structural and immunological profiles, supporting its potential for further vaccine development. Experimental studies in appropriate <i>in vitro</i> and <i>in vivo</i> models are warranted to further assess its immunogenicity, safety, and protective potential.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1934834"},"PeriodicalIF":5.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of a standardized cranberry supplement on overactive bladder symptoms and urobiome alterations in young women: a randomized, double-blind, placebo-controlled pilot trial.","authors":"Ayaka Ito, Shohei Akagawa, Yuko Akagawa, Shoji Tsuji, Shogo Kato, Sohsaku Yamanouchi, Kazunari Kaneko","doi":"10.3389/fcimb.2026.1952206","DOIUrl":"10.3389/fcimb.2026.1952206","url":null,"abstract":"<p><strong>Introduction: </strong>Urobiome dysbiosis has been implicated in the pathogenesis of overactive bladder (OAB). In this study, the efficacy of a cranberry supplement for OAB symptoms was investigated, and concurrent urobiome alterations were evaluated in young women.</p><p><strong>Methods: </strong>This double-blind, randomized, placebo-controlled trial enrolled 26 women (median age, 23 years) with OAB (Overactive Bladder Symptom Score [OABSS] ≥ 3), who received either a cranberry supplement (36 mg proanthocyanidins per day) or placebo for 4 weeks. Clinical efficacy was assessed using the OABSS reduction rate, and urobiome composition was evaluated by 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Twenty-five participants were included in the analysis. At 4 weeks, the OABSS reduction rate was greater in the cranberry group than in the placebo group (median, 66.7% vs. 40.0%; p = 0.039). At baseline, the urobiome was dominated by <i>Lactobacillus</i> (median relative abundance, 64.2%). After cranberry supplementation, the relative abundance of <i>Lactobacillus</i> decreased within the cranberry group (median change, -4.39%; p = 0.027; q = 0.096). No compositional changes were observed in the placebo group.</p><p><strong>Conclusions: </strong>Cranberry supplementation was associated with greater improvement in OAB symptoms than was observed with placebo in young women, while a decrease in <i>Lactobacillus</i> relative abundance was observed within the cranberry group. Given the small sample size of this exploratory pilot trial and the limited species-level resolution of 16S rRNA sequencing, these concurrent findings should be regarded as hypothesis-generating and warrant further investigation.</p><p><strong>Clinical trial registration: </strong>https://www.umin.ac.jp/ctr/, identifier UMIN000057544.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1952206"},"PeriodicalIF":5.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut mycobiome dysbiosis in digestive system cancers: immune remodeling and translational implications.","authors":"LingBo Ma, Zhen Wang, Jie Mao","doi":"10.3389/fcimb.2026.1902754","DOIUrl":"10.3389/fcimb.2026.1902754","url":null,"abstract":"<p><p>Fungal dysbiosis has been reported in colorectal cancer (CRC), gastric cancer (GC), and pancreatic ductal adenocarcinoma (PDAC), but evidence strength differs substantially by tumor type and model system. Human CRC studies provide the broadest ecological evidence, including altered fungal community structure and fungal-bacterial networks. Human GC evidence is mainly cross-sectional and identifies <i>Candida albicans</i> as a candidate tissue-associated signal rather than a proven driver. In PDAC, human tissue studies report fungal signals, whereas causal support for <i>Malassezia</i>-mannose-binding lectin (MBL)-complement and fungal IL-33/type 2 immunity derives principally from mouse perturbation models. This narrative review synthesizes cancer-specific observations, fungal sensing, epithelial injury, immune remodeling, cross-kingdom interactions, and translational implications. We emphasize that low fungal biomass, contamination, transient dietary or environmental fungi, non-standardized sequencing, spatial uncertainty, and reverse causation limit interpretation. Fungal detection does not establish viability, colonization, or tumor causation. Clinical translation will require standardized controls, absolute fungal-load measurements, spatial confirmation, longitudinal cohorts, functional validation, and external testing of whether fungal features add value beyond established clinical, bacterial, metabolic, imaging, and immune markers.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1902754"},"PeriodicalIF":5.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13684329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metagenomic next-generation sequencing in tuberculous periprosthetic joint infection: pathogen-detection yield and clinical characteristics compared with common bacterial PJI.","authors":"Jiayu Li, Yuntao Liao, Xiaolin Li, Lan Lin, Yafei Liu, Wenbo Li, Zida Huang, Zhaoyang Wu, Xinyu Fang, Wenming Zhang","doi":"10.3389/fcimb.2026.1935713","DOIUrl":"10.3389/fcimb.2026.1935713","url":null,"abstract":"<p><strong>Objective: </strong>To compare the pathogen-detection yield of metagenomic next-generation sequencing (mNGS) and conventional culture in tuberculous periprosthetic joint infection (TB-PJI) and common bacterial PJI (CB-PJI), and to characterize clinical differences and exploratory associations with TB-PJI.</p><p><strong>Methods: </strong>A retrospective cohort included 197 patients with periprosthetic joint infection treated between January 2016 and June 2024 who underwent both conventional culture and mNGS during the same diagnostic or surgical episode. Patients were classified as CB-PJI (n=178) or TB-PJI (n=19). Paired pathogen-detection rates were compared using McNemar's test. Exploratory multivariable associations with TB-PJI were assessed using Firth penalized logistic regression with the Charlson Comorbidity Index (CCI) modeled continuously.</p><p><strong>Results: </strong>In CB-PJI, mNGS showed a higher pathogen-detection rate than conventional bacterial culture (94.4% vs. 78.1%, P<0.001). In TB-PJI, Mycobacterium tuberculosis complex (MTBC) was detected by mNGS in 17/19 cases (89.5%) and recovered by mycobacterial culture in 5/19 cases (26.3%; P<0.001); 12/19 cases were mNGS-positive/mycobacterial-culture-negative. In the primary exploratory Firth model, each 1-point increase in CCI was associated with higher odds of TB-PJI (aOR=2.39, 95% CI: 1.51-4.10, P<0.001), whereas each 10% increase in SF PMN% was associated with lower odds (aOR=0.722, 95% CI: 0.564-0.917, P = 0.009); BMI was not statistically significant. Drug-related complications were more frequent in TB-PJI (42.1% vs. 11.8%, P = 0.002), while the 2-year infection recurrence rate did not differ significantly (15.8% vs. 7.9%, P = 0.216).</p><p><strong>Conclusion: </strong>In this selected retrospective cohort, mNGS provided a higher pathogen-detection yield than conventional culture, particularly for TB-PJI. Higher CCI and lower SF PMN% were exploratory clinical associations with TB-PJI and should not be interpreted as validated diagnostic thresholds. mNGS should be considered an adjunct to mycobacterial culture, molecular testing, and histopathology rather than a stand-alone diagnostic test.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1935713"},"PeriodicalIF":5.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}