Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Beyond susceptibility testing: traditional Chinese medicine-associated compounds as candidate antibiotic adjuncts in chronic-wound biofilms.","authors":"Nan Lu, Ru-Ping Zhao, Jun-Jie He, Yi-Ping Zhou, Jin-Sheng Zhang","doi":"10.3389/fcimb.2026.1991374","DOIUrl":"10.3389/fcimb.2026.1991374","url":null,"abstract":"<p><p>Chronic-wound infections may respond poorly even when routine testing shows that the infecting organism remains susceptible. In tissue, bacteria occupy aggregates shaped by oxygen and nutrient gradients, host material, diabetes-associated chemistry and uneven antibiotic exposure. These conditions can slow killing and favour small-colony variants or intracellular survival, particularly in Staphylococcus aureus. Human evidence for these phenotypes is strongest in diabetes-related foot infection and associated bone, whereas evidence for intracellular Pseudomonas aeruginosa in wounds remains largely experimental. We examined whether chemically defined compounds associated with traditional Chinese medicine (TCM) might improve antibiotic performance in this setting. The most persuasive preclinical studies connect a compound to antibiotic entry, target regulation or viable killing. Weaker reports rely on early-biofilm biomass, checkerboard interaction or formulation effects that cannot be assigned to the phytochemical itself. Cinnamaldehyde, chenodeoxycholic acid, sodium houttuyfonate and 5, 8-dihydroxy-1, 4-naphthoquinone provide useful mechanistic or infected-wound leads, but the evidence remains fragmented across organisms and models. As of 12 August 2026, we found no controlled human study showing that a chemically defined TCM-associated compound used as an antibiotic adjunct clears mature chronic-wound biofilm, prevents infectious relapse or safely reduces antibiotic exposure. Progress now depends on testing fewer, well-defined combinations in mature polymicrobial systems. Such studies should measure post-treatment regrowth, infection-site exposure and tissue compatibility alongside bacterial killing.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1991374"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215501","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":"Association analysis of CCL5, P2RX7, and SP110 gene polymorphisms with inactive pulmonary tuberculosis.","authors":"Fengting Chen, Haitao Wang, Junfeng Ren, Jifeng Cao, Chong Liu, Shanying Tong, Changdong Wu","doi":"10.3389/fcimb.2026.1937385","DOIUrl":"10.3389/fcimb.2026.1937385","url":null,"abstract":"<p><strong>Background: </strong>Host genetic background plays a crucial role in Mycobacterium tuberculosis infection and the development of pulmonary tuberculosis. This study aims to investigate the association between the polymorphisms of the <i>CCL5</i>, <i>P2RX7</i>, and <i>SP110</i> genes and the pathogenesis of inactive pulmonary tuberculosis.</p><p><strong>Methods: </strong>Identify hub genes based on GEO transcriptome data. A case-control study was conducted, enrolling 154 patients with inactive Pulmonary Tuberculosis (comprising 84 untreated and 70 treated cases) and 87 controls. Peripheral blood DNA was extracted, and six polymorphic loci within the <i>SP110</i>, <i>CCL5</i>, and <i>P2RX7</i> genes were genotyped using PCR and DNA sequencing. Univariate and multivariate logistic regression analyses were performed to evaluate genotypic and allelic distributions.</p><p><strong>Results: </strong>Two hub genes, <i>SP110</i> and <i>CCL5</i>, were identified from the transcriptome data. At the <i>SP110</i> rs9061 locus, the frequency of the A allele was lower in the untreated group compared to the control group, showing nominal significance (<i>P</i> = 0.015); however, this association did not remain significant after FDR correction (<i>P_FDR</i>  = 0.09). After adjusting for multiple factors, the A allele showed a nominally significant association with reduced IPTB risk (<i>P</i> = 0.042). Furthermore, although interaction (<i>P</i> = 0.682) and homogeneity tests (<i>P</i> = 0.584) were not statistically significant, limited subgroup sample sizes preclude claiming true homogeneity across subgroups. CMH stratified analysis revealed a nominally significant association (<i>P</i> = 0.034). Importantly, these adjusted results do not overcome the multiple-testing issue.</p><p><strong>Conclusions: </strong>The A allele at the <i>SP110</i> rs9061 locus may show a suggestive and exploratory association with decreased susceptibility to inactive pulmonary tuberculosis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1937385"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215484","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":"Mortality of <i>Candida auris</i> candidemia compared with non-<i>auris</i> candidemia: a systematic review and meta-analysis.","authors":"Jing Chen, Na Xiao, Qian Xiang, Yan Luo, Hui Wang, Tian-Fen Liao","doi":"10.3389/fcimb.2026.1952600","DOIUrl":"10.3389/fcimb.2026.1952600","url":null,"abstract":"<p><strong>Background: </strong><i>Candida auris</i> has emerged as a globally significant healthcare-associated fungal pathogen. Although descriptive studies have reported high mortality for candidemia caused by <i>C. auris</i>, whether the mortality differs from non-<i>auris</i> candidemia remains unclear. We conducted this meta-analysis to compare the mortality between patients with <i>C. auris</i> and non-<i>auris</i> candidemia.</p><p><strong>Methods: </strong>We searched PubMed (including MEDLINE), Embase, and Web of Science databases for relevant studies published before June 2026. A random-effects model was used for meta-analysis.</p><p><strong>Results: </strong>A total of 16 articles were included in this meta-analysis. In the pooled crude analysis, mortality was significantly lower in patients with <i>C. auris</i> candidemia than in those with non-<i>auris</i> candidemia (OR = 0.77, 95% CI 0.67-0.90). Subgroup analyses showed significant geographic variation (P for interaction = 0.019), with lower mortality observed in studies from Turkey, the Middle East and the Americas, but not in South Asia and Africa. Despite lower mortality, <i>C. auris</i> candidemia was associated with prolonged hospitalization in descriptive analysis.</p><p><strong>Conclusion: </strong>In this meta-analysis of crude estimates, mortality was significantly lower in patients with <i>C. auris</i> candidemia than in those with non-<i>auris</i> candidemia. However, prolonged hospitalization in <i>C. auris</i> infection highlights its medical resource burden. For clinicians, management of <i>C. auris</i> candidemia should focus on timely diagnosis, appropriate antifungal therapy, and strengthened infection prevention, especially in cases of long-term hospitalization.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1952600"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215669","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":"Distinct time-dependent <i>S</i>. Typhi-specific CD8⁺ T cell programs are associated with clinical outcome following Ty21a immunization and wild-type <i>S</i>. Typhi challenge in humans.","authors":"Jayaum S Booth, Rekha R Rapaka, Monica A McArthur, Stephanie Fresnay, Thomas C Darton, Bing Guo, Claire S Waddington, Myron M Levine, Andrew J Pollard, Marcelo B Sztein","doi":"10.3389/fcimb.2026.1924754","DOIUrl":"10.3389/fcimb.2026.1924754","url":null,"abstract":"<p><strong>Introduction: </strong>CD8⁺ T cells are essential components of the adaptive immune system that play a critical role in determining the clinical severity of typhoid disease by directly killing <i>Salmonella enterica</i> serovar Typhi (<i>S</i>. Typhi)-infected cells, producing cytokines, chemokines, and establishing memory responses that have been linked to clinical outcome in a controlled human infection model (CHIM) of typhoid. Despite decades of extensive research, the role of memory CD8⁺ T (T_M) cells and its subsets as correlates of protection against <i>S</i>. Typhi infection and typhoid disease remains incompletely understood.</p><p><strong>Methods: </strong>In this study, we used specimens from a typhoid CHIM study in which participants who were immunized with live attenuated <i>S</i>. Typhi vaccine, Ty21a, were subsequently challenged with virulent <i>S</i>. Typhi. Some participants developed typhoid disease (TD) and some did not (NoTD), allowing us to assess the immune program of CD8⁺ T_M subsets involved in the prevention of typhoid disease using mass cytometry, CyTOF.</p><p><strong>Results and discussion: </strong>Our high-dimensional profiling data showed that TD and NoTD participants followed divergent memory CD8⁺ T cell trajectories. We observed that CD8⁺ T clusters from NoTD participants are enriched for early multifunctional, protection-associated programs while TD participants exhibited a distinct clustering associated with susceptibility states. Specifically, using unsupervised dimensionality reduction and clustering analysis, T-REX, and feature-ranking analyses, we identified memory CD8⁺ T cell subsets including effector/memory (T_EM), T central/memory (T_CM) and CD45RA+ T_EM (T_EMRA) associated with clinical outcomes. CD8⁺ T_EM from NoTD participants were generally characterized by stronger effector-associated signatures such as CXCR3, IL-17A, TNFα, and MIP1b. In contrast, CD8⁺ T_EM from TD participants showed CCR6- and integrin α4β7-biased immune profiles. Detailed analysis revealed that CD8⁺ T_CM and T_EMRA subsets also contained distinct outcome-associated states. These patterns were confirmed by conventional supervised gating that validated both protection-associated and susceptibility-associated marker combinations across CD8⁺ T_EM, T_CM and T_EMRA subsets. These data suggest that: 1. Protection and susceptibility are not restricted to one CD8⁺ T cell subset but rather are distributed across the broader CD8⁺ T memory landscape and, 2. Typhoid clinical outcome is associated with qualitatively distinct CD8⁺ T memory programs rather than differences only in the magnitude of the overall anti-<i>S</i>. Typhi immune response.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1924754"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215604","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":"Prediction of vancomycin-resistant phenotype in ICU-onset sterile-site <i>Enterococcus</i>-positive cultures: development and pseudo-temporal validation of a clinical prediction model using MIMIC-IV.","authors":"Wenhao Sun, Xiao-Lan Gu, Qingmei Ma, Jinxia Hou, Yanbin Chang","doi":"10.3389/fcimb.2026.1935284","DOIUrl":"10.3389/fcimb.2026.1935284","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin-resistant enterococci challenge intensive care. During the interval between organism identification and final phenotypic antimicrobial susceptibility testing, clinicians must balance delayed effective anti-VRE therapy against unnecessary anti-VRE exposure. We aimed to develop and pseudo-temporally validate a model for the vancomycin-resistance phenotype of the index isolate; the model does not determine whether the isolate represents clinically significant infection.</p><p><strong>Methods: </strong>In this retrospective MIMIC-IV cohort, adult ICU admissions with a sterile-site <i>Enterococcus</i>-positive culture obtained more than 48 hours after ICU admission were assigned by de-identified anchor-year group to development (groups labelled 2008-2016; n = 552) or pseudo-temporal validation (2017-2022; n = 259). Predictors were restricted to information available by specimen collection. Elastic Net with bootstrap stability screening retained 19 of 141 candidates; four tree-based models were comparators.</p><p><strong>Results: </strong>Among 811 admissions (507 resistant isolates; prevalence, 62.5%), Elastic Net achieved a validation AUROC of 0.835 (95% CI, 0.778-0.889) and calibration slope of 0.91 (0.71-1.18). Tree-model AUROCs were 0.842-0.855; non-significant pairwise DeLong tests were evidence insufficient to detect differences, not evidence of equivalence. Removing both species indicators reduced AUROC to 0.657 (DeLong <i>P</i> < 0.001). Development-OOF-fitted Platt scaling improved validation slopes for Random Forest, XGBoost, and CatBoost from 1.41, 2.41, and 1.46 to 0.94, 1.02, and 1.01. At the Youden index threshold, Elastic Net sensitivity was 0.884 and specificity was 0.690. In exploratory decision-curve analysis, its net benefit did not exceed treat-all at thresholds 0.10 or 0.20; the paired difference was 0.044 (95% CI, 0.014-0.071) at 0.30.</p><p><strong>Conclusions: </strong>The model predicts isolate resistance phenotype, not adjudicated infection, and is not a stand-alone treatment rule. These estimates are specific to a single-center cohort with high VRE prevalence. Independent external validation, local recalibration, clinical adjudication, and periodic updating are prerequisites for use.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1935284"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215294","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":"Disrupting <i>Salmonella</i> colonization and resistance: probiotic cell-free supernatants inhibit biofilm formation and invasion in meat and human isolates.","authors":"Azza S El-Demerdash, Mervat A Said, Mahmoud M Hazaa, Mahmoud M Amer, Yasmen F Mahran, Hadil Alahdal, Munirah M Alhammadi, Ahmed G Abdelhamid","doi":"10.3389/fcimb.2026.1889179","DOIUrl":"10.3389/fcimb.2026.1889179","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;&lt;i&gt;Salmonella enterica&lt;/i&gt; remains a paramount global public health threat due to the rapid emergence of multi-drug and pan-drug resistant (PDR) strains transmitted through the food supply chain. This study adopted a One Health cross-sectional framework to investigate the occurrence and biocontrol of PDR &lt;i&gt;Salmonella enterica&lt;/i&gt; serovars (&lt;i&gt;S.&lt;/i&gt; Enteritidis, &lt;i&gt;S.&lt;/i&gt; Kentucky, and &lt;i&gt;S.&lt;/i&gt; Anatum) isolated from clinical gastroenteritis cases and retail meat products in Egypt.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical samples (n=20) from gastroenteritis patients were screened for PDR &lt;i&gt;Salmonella&lt;/i&gt; and confirmed via &lt;i&gt;invA&lt;/i&gt; gene PCR in addition to six PDR isolates previously from meat samples. Biocontrol efficacy was evaluated using cell-free spent media (CFSM; postbiotic preparations) derived from a consortium of probiotic strains. Chemical profiling of CFSM was executed via High-Performance Liquid Chromatography (HPLC). Antimicrobial activity, minimum inhibitory concentrations, and biofilm formation were quantified. Host cell invasion was assessed using a gentamicin protection assay in human Caco-2 intestinal epithelial cells. Ultrastructural alterations were examined via Transmission Electron Microscopy (TEM). Transcriptomic mechanisms were elucidated via RT-qPCR targeting biofilm regulators (&lt;i&gt;csgD&lt;/i&gt;, &lt;i&gt;sdiA&lt;/i&gt;) and &lt;i&gt;Salmonella&lt;/i&gt; Pathogenicity Island 1 (SPI-1) invasion genes (&lt;i&gt;hilA&lt;/i&gt;, &lt;i&gt;invF&lt;/i&gt;, &lt;i&gt;prgH&lt;/i&gt;, and &lt;i&gt;sipA&lt;/i&gt;).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CFSM from &lt;i&gt;Lactobacillus helveticus&lt;/i&gt; EMCC 1654 and &lt;i&gt;Lactobacillus plantarum&lt;/i&gt; CCUG 30503 demonstrated marked antibacterial and antibiofilm activity. At sub-inhibitory concentrations (10% v/v), CFSM significantly attenuated biofilm formation and reduced host-cell invasion efficiency in &lt;i&gt;S.&lt;/i&gt; Kentucky to 0.08% relative to untreated controls. TEM micrographs confirmed severe cell envelope disintegration, membrane detachment, and cytoplasmic leakage in CFSM-treated cells. RT-qPCR analysis revealed significant downregulation of the master biofilm regulator &lt;i&gt;csgD&lt;/i&gt; (fold-change: 0.002) and the quorum-sensing receptor &lt;i&gt;sdiA&lt;/i&gt; (fold-change: 0.02). Furthermore, key SPI-1 invasion genes were markedly repressed, including &lt;i&gt;hilA&lt;/i&gt; (0.188), &lt;i&gt;invF&lt;/i&gt; (0.001), &lt;i&gt;prgH&lt;/i&gt;, and &lt;i&gt;sipA&lt;/i&gt; (0.037). Quantitative HPLC profiling of &lt;i&gt;L. plantarum&lt;/i&gt; CCUG 30503 CFSM- the lead candidate for downstream mechanistic analysis- identified a multi-organic acid cocktail dominated by lactic (1.89 mg/mL), succinic (1.53 mg/mL), and acetic (1.11 mg/mL) acids.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;&lt;i&gt;Lactobacillus&lt;/i&gt;-derived postbiotics (CFSM) function as effective antivirulence agents that disrupt both the transcriptional networks governing biofilm synthesis and SPI-1-mediated host invasion, while physically compromising bacterial cell wall integrity. These findings highlight probiotic CFSM as a sustainable, non-antibiotic strategy to","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1889179"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215620","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":"Immune mechanisms underlying endothelial and placental dysfunction in leptospirosis during pregnancy.","authors":"Cecilia Nieves, Elsa-Patricia Rondon, Aindrila Kazi, Mariane Bertagnolli","doi":"10.3389/fcimb.2026.1952734","DOIUrl":"10.3389/fcimb.2026.1952734","url":null,"abstract":"<p><p>Leptospirosis is a zoonotic disease caused by pathogenic bacteria of the genus <i>Leptospira</i> and represents a major public health concern worldwide. Although its systemic manifestations are well documented, the consequences of leptospirosis for reproduction and pregnancy, particularly in humans, remain poorly understood. This narrative review summarizes the principal reproductive outcomes associated with leptospirosis and examines the mechanisms that may contribute to pregnancy complications. In livestock, leptospirosis is a well-established cause of reproductive failure, including abortion and infertility, and is frequently associated with persistent infection and colonization of the genital tract. In humans, where available evidence remains limited, adverse pregnancy outcomes may be mediated predominantly by systemic endothelial injury, inflammatory activation, and immune dysregulation leading to impaired placental perfusion, rather than solely by direct infection of placental tissues. We therefore integrate evidence from veterinary research and human studies to examine the biological mechanisms through which leptospirosis may contribute to pregnancy complications and potentially overlap with other pregnancy-related disorders. A One Health approach that combines human, animal, and environmental data is essential to improve disease prevention, reduce its reproductive burden, and protect the health of pregnant individuals and their developing fetuses.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1952734"},"PeriodicalIF":5.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215603","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":"Transcriptomic evidence of an IFN-gamma-associated inflammatory state in active visceral leishmaniasis: an exploratory comparison with pediatric HLH.","authors":"Taoli Suo, Jing Zhang, Yanli Chen, Hongyu Shi, Haiyan Lu","doi":"10.3389/fcimb.2026.1924856","DOIUrl":"10.3389/fcimb.2026.1924856","url":null,"abstract":"<p><strong>Background: </strong>Visceral leishmaniasis (VL) can progress to secondary hemophagocytic lymphohistiocytosis (HLH), but transcriptomic similarities between active VL and pediatric HLH remain uncertain.</p><p><strong>Methods: </strong>We integrated VL whole-blood expression data (GSE125992), sorted CD68-positive monocyte bulk-expression data from pediatric HLH and severe sepsis (GSE150707), and supportive Leishmania-infected mouse spleen single-cell data (GSE240385). Differential expression, pathway enrichment, an exploratory 132-gene HLH-versus-sepsis-derived ssGSEA score, FARDEEP-LM22 deconvolution, signature-excluded WGCNA, CellChat, and a refitted three-gene classifier were evaluated.</p><p><strong>Results: </strong>Active VL showed IFN-gamma-associated expression changes, including higher CXCL9 and CXCL10. The exploratory 132-gene score was higher in ActiveCase than EHC samples (Mann-Whitney P = 0.000637). Across 22 deconvolved cell types, only M1 macrophages showed an FDR-supported positive correlation with this score (rho = 0.787, BH q = 0.000503). After all 132 score genes were excluded before network construction, a 124-gene magenta module remained associated with the score (rho = 0.837, BH q = 4.29 × 10^-5). A refitted IFNG/GBP5/MX2 classifier achieved a same-study validation AUC of 0.917 (bootstrap 95% CI 0.733-1.000), but the validation set contained only 16 samples.</p><p><strong>Conclusion: </strong>These public datasets support an IFN-gamma-associated inflammatory state in active VL and exploratory cross-compartment convergence with pediatric HLH. The 132-gene score, deconvolution, network, and classifier results are hypothesis-generating and do not establish HLH specificity, cellular causality, independent external validity, or clinical HLH prediction.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1924856"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215512","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":"Alterations in <i>Salmonella diarizonae</i> proteome after exposure to human serum.","authors":"Eva Krzyżewska-Dudek, Katarzyna Kapczyńska, Paweł Pasikowski, Bartłomiej Dudek, Jacek Rybka","doi":"10.3389/fcimb.2026.1875815","DOIUrl":"10.3389/fcimb.2026.1875815","url":null,"abstract":"<p><p><i>Salmonella</i> bacteria can modify structures of various cell envelope components to survive in extremely adverse environments and evade the host's immune response. Bacterial resistance to serum is crucial for the development of systemic infections. Here, we investigated how long-term exposure to human serum alters the length of lipopolysaccharide and the outer membrane proteome shape of <i>Salmonella diarizonae</i>. Experiments have shown that prolonged exposure to human serum affects the survival rate of <i>S. diarizonae</i> but not the average length of lipopolysaccharide. Interestingly, after the analysis of preparations of outer membrane proteins we have shown, that multiple passages in human serum induced changes in the outer membrane proteome. Among the proteins with higher abundance compared to the strain prior to serum exposure, proteins described as complement resistance proteins of <i>Salmonella</i> bacteria could be identified (PagC, PgtE). Additionally, an upregulation of proteins involved in the biosynthesis of polysaccharides (RfbD, RfbA, RfbF, YaeD, PmrF, WzzE) was observed, suggesting that modifications in the structure of lipid A and modifications in the length of the enterobacterial common antigen (ECA) may be involved in the protection of <i>S. diarizonae</i> from the bactericidal action of human serum.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1875815"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215526","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":"KLRG1⁺CD28^⁻CD57⁺ Ag85A-specific CD8⁺ T cells mark a severity-associated terminal-differentiation imprint in pulmonary tuberculosis.","authors":"Jiaming Wu, Sufang Chen, Rui Qiang, Longji Cheng, Minyan Yao, Zhen Zhang, Xin Yu, Junchi Xu, Jianping Zhang","doi":"10.3389/fcimb.2026.1938907","DOIUrl":"10.3389/fcimb.2026.1938907","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary tuberculosis (PTB) is characterized by prolonged host-pathogen interaction, chronic granulomatous inflammation, and sustained exposure to Mycobacterium tuberculosis (Mtb) antigens. How Mtb antigen-specific CD8⁺ T cell differentiation states relate to clinical disease activity and severity remains incompletely defined. This study investigated the clinical relevance of a terminal differentiation-associated phenotype within Ag85A-specific CD8⁺ T cells across clinically defined states of Mtb infection and disease.</p><p><strong>Methods: </strong>A total of 124 participants were enrolled, including 55 patients with PTB, 33 individuals with latent tuberculosis infection (LTBI), and 36 healthy controls (HCs). Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify KLRG1⁺CD28^⁻CD57⁺ cells among HLA-A*02:01-restricted Ag85A₄₈-₅₆ tetramer⁺CD8⁺ T cells. Associations with active disease, sputum smear status, clinical severity, selected host-status parameters, and exploratory treatment-related outcomes were assessed.</p><p><strong>Results: </strong>Patients with PTB showed a significantly higher proportion of KLRG1⁺CD28^⁻CD57⁺ Ag85A-specific CD8⁺ T cells than HCs. This phenotype was enriched in active PTB and was associated with clinically relevant features of disease burden, including sputum smear positivity, higher smear grade, lymphocyte imbalance, and severe pulmonary involvement. Patients with severe PTB had higher proportions of this subset than patients with non-severe PTB. In receiver operating characteristic analysis, this phenotype showed exploratory in-cohort discriminative potential for distinguishing severe from non-severe PTB, with an apparent area under the curve of 0.8333 (95% CI, 0.7268-0.9398; P<0.0001); patient-level bootstrap resampling yielded a bias-corrected AUC of 0.8333.</p><p><strong>Conclusions: </strong>The accumulation of KLRG1⁺CD28^⁻CD57⁺ Ag85A-specific CD8⁺ T cells is closely associated with active and clinically severe PTB. Rather than establishing a causal mechanism, these findings identify an antigen-specific, terminal differentiation-associated CD8⁺ T-cell phenotype as a potential translational immune correlate of disease severity in human Mtb infection. Its discriminative ability should be regarded as preliminary and requires external validation in larger, prospective, and independently recruited cohorts.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"16 ","pages":"1938907"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215652","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}