Medical Microbiology and Immunology最新文献

{"title":"Genotypic investigation of Mycobacterium leprae in patients with relapsing leprosy in Mato Grosso, Brazil.","authors":"Roque Rafael de Oliveira Neto, Agenor de Castro Moreira Dos Santos Júnior, Brenno Vinicius Martins Henrique, Ciro Martins Gomes, Amílcar Sabino Damazo","doi":"10.1007/s00430-025-00864-w","DOIUrl":"10.1007/s00430-025-00864-w","url":null,"abstract":"<p><p>Leprosy is a chronic disease that leads to significant neurological damage and disabilities. Drug resistance is a major challenge in controlling the disease. Mutations in the folP1, rpoB, and gyrA genes can confer resistance to dapsone, rifampicin, and quinolones, respectively. The aim of this study was to identify mutations in these drug-resistance genes in Mycobacterium leprae among patients in the state of Mato Grosso, Brazil, and to investigate potential related clinical characteristics. A total of 60 patients from various cities in Mato Grosso were clinically evaluated. Following skin biopsies, samples underwent bacilloscopy and PCR analysis, resulting in 34 positive samples. Fourteen patients were undergoing multidrug therapy (MDT), and 4 exhibited active reactional states during the investigation. Relapse was identified in 8 patients. High-quality sequences were generated for the rpoB, folP1, and gyrA gene fragments. We observed a single alteration in the gyrA gene sequence, specifically a cytosine-to-thymine transition at position 297. This alteration was detected in 10 patients, all classified as multibacillary. The analysis indicated that 5 of these patients with relapse had bacilli with the gyrA gene polymorphism, including one patient experiencing erythema nodosum leprosum. Another 4 patients were already on their second MDT treatment regimen, and one had been under treatment for 6 months. In conclusion, while classical resistance mutations were not prevalent in the cohort, the identification of synonymous SNPs in the gyrA gene has significant potential as a surrogate marker for particular mycobacterial subpopulations linked to relapse.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":"1"},"PeriodicalIF":3.1,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762757","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":"Commensal Peptoniphilus harei induce activation of monocytes via TLR2/CD14 signalling in whole blood.","authors":"Tobias Schmidt, Inga-Maria Frick, Lotta Happonen, Ariane Neumann","doi":"10.1007/s00430-025-00859-7","DOIUrl":"10.1007/s00430-025-00859-7","url":null,"abstract":"<p><p>Myeloid cells, such as monocytes, are central in the immune response to infections. However, limited knowledge exists regarding the inflammatory response to Gram-positive anaerobic cocci (GPAC).To explore the ability of GPACs to induce monocyte activation, we compared two GPAC species, Parvimonas micra and Peptoniphilus harei, with E. coli, a major cause of bloodstream infections. We stimulated whole blood with heat-killed bacteria or conditioned medium (CM) and analysed monocytes for signs of activation by flow cytometry. The mechanisms were explored using anti-CD14- or anti-TLR2 antibodies. Finally, to investigate potential pathogen-associated molecular patterns in CM, we performed mass spectrometry (MS).Our findings revealed that P. harei significantly induced activation of monocytes, as evidenced by increased expression of activation markers (PDL1, HLA-DR and CD11b), phosphorylation of members of signalling pathways (NFκBp65, p38 and Akt) and production of cytokines (IL-1β, TNF, IL-6). Interestingly, P. micra had minimal impact on monocyte activation, and we thus focused on P. harei. Pre-treatment with anti-CD14 attenuated the activation of monocytes by heat-killed P. harei. Moreover, P. harei CM also induced clear monocyte activation, though, in contrast to heat-killed P. harei, this activation was dependent on TLR2 signalling. MS analysis of CM primarily identified four proteins possibly associated with monocyte activation. Finally, we also explored neutrophil activation and found a similar activation pattern to that of monocytes, suggesting that our observations are not exclusive to monocytes.Our study demonstrates that P. harei induce prominent activation of monocytes in blood, highlighting a pathogenic potential of these otherwise harmless perceived bacteria.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"52"},"PeriodicalIF":3.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635390","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":"YopP modulates bacterial virulence and systemic dissemination in Peyer´s patches during murine Yersinia enterocolitica infection.","authors":"Juan Eduardo Silva, Ricardo Javier Eliçabe, Roberto Carlos Davicino, Marisol Velazquez, Agustina Medina, María Silvia Di Genaro","doi":"10.1007/s00430-025-00861-z","DOIUrl":"10.1007/s00430-025-00861-z","url":null,"abstract":"<p><p>Yersinia enterocolitica (Ye) typically causes gastroenteritis and mesenteric lymphadenitis and can also spread extra-intestinally. Yersinia outer protein P (YopP) has been shown to induce cytotoxicity and suppress pro-inflammatory responses in in vitro studies. However, the role of YopP during in vivo Ye infection remains incompletely understood. Here, we show that, contrary to expectations for a virulence factor, a YopP-deficient strain (Ye ΔyopP) increases bacterial dissemination from Peyer's patches (PP) to mesenteric lymph nodes (MLN) and the spleen in intragastrically infected mice. Additionally, inhibition of cytotoxicity by suramin treatment in mice promoted wild-type Ye (Ye WT) dissemination to levels comparable to Ye ΔyopP. Moreover, the absence of YopP enhanced neutrophil and macrophage infiltration and increased pro-inflammatory cytokine production in PP, while decreasing IL-10 levels in PP, MLN and the spleen. Notably, the CD11b⁺ dendritic cell (DC) subpopulation in PP following Ye ∆yopP infection did not reach the levels observed in Ye WT. However, Ye-carrying DCs were significantly elevated after infection with GFP-expressing Ye ∆yopP (Ye ∆yopP GFP⁺). Blocking DC migration by FTY720 treatment in Ye ΔyopP-infected mice significantly reduced the MLN bacterial burden, indicating that YopP regulates Ye-transporting DCs from PP to MLN. Overall, our findings provide insights into how YopP participates in host-pathogen interactions, seemingly benefiting the host while simultaneously facilitating bacterial evasion from early immune clearance. These findings contribute to understanding the impact of YopP on the clinical outcome of Ye infection.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"51"},"PeriodicalIF":3.1,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541220","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":"Furamidine enhances IL-23-mediated autophagic response through IL-23R-TYK2-STAT3-dependent regulation of intracellular Ca²⁺ level to facilitate mycobacterial clearance in human macrophages.","authors":"Salina Patel, Mousumi Das, Dev Kiran Nayak, Pramathesh Kumar Dandsena, Mustafeez Ali Quaderi, Amit Mishra, Surajit Das, Ramandeep Singh, Lincoln Naik, Rohan Dhiman","doi":"10.1007/s00430-025-00860-0","DOIUrl":"10.1007/s00430-025-00860-0","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis (TB), subverts host immune responses to establish persistent infection by influencing cytokine production. An effective and balanced cytokine response is crucial for eliminating the pathogen, whereas disruptions in this balance can lead to increased vulnerability to infection. Therefore, developing immunomodulatory agents to steer host immunity toward the adequate clearance of M. tb offers a promising strategy for limiting TB. This study investigates the immunomodulatory effects of Furamidine in response to regulating mycobacterial infection in differentiated THP-1 cells by activating Interleukin-23 (IL-23) signaling. Initially, we checked the immunoregulatory effect of Furamidine and found a substantial increase in the expression of IL-23 at mRNA and protein levels in uninfected and mycobacteria-infected dTHP-1 cells. Neutralization of IL-23 led to a rise in bacterial survival in the cells, confirming the physiological role of IL-23 in clearing mycobacteria in Furamidine-treated macrophages. It was further elucidated that Furamidine increased the receptors IL-12Rβ1 and IL-23R, essential for IL-23 signaling. IL-23R activation, in turn, phosphorylated its downstream effectors TYK2 and STAT3, which regulated the intracellular Ca²⁺ level. Neutralization of IL-23 or pharmacological inhibition of TYK2 and STAT3 by Deucravacitinib and Stattic hampered the process of autophagy by hindering the IL-23 signaling and leading to an increase in the survival of mycobacteria, pointing to the essential role of IL-23 in response to mycobacteria elimination from the cells. These findings revealed that Furamidine promotes host defense in mycobacterial infection by enhancing IL-23-mediated autophagy via the IL-23R/pTYK2/pSTAT3-Ca²⁺ pathway.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"50"},"PeriodicalIF":3.1,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513250","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":"Microbiome therapeutic PMC101 inhibits the translocation of carbapenem-resistant Klebsiella while enhancing eubiosis in antibiotic-induced dysbiosis mice.","authors":"Hanieh Tajdozian, Hoonhee Seo, Sukyung Kim, Md Abdur Rahim, Hyun A Park, Faezeh Sarafraz, Youjin Yoon, Hokyoung Kim, Indrajeet Barman, Chae-Eun Park, Fatemeh Ghorbanian, Soyeon Lee, Hwal Rim Jeong, Ho-Yeon Song","doi":"10.1007/s00430-025-00858-8","DOIUrl":"10.1007/s00430-025-00858-8","url":null,"abstract":"<p><p>Carbapenem-resistant Enterobacteriaceae (CRE), known for their extensive antibiotic resistance, pose a severe global medical threat. Therefore, developing novel therapeutics beyond conventional antibiotics is urgently needed, and the importance of microbiome therapeutics is increasingly being recognized. This study explores the expanded systemic efficacy of PMC101, a microbiome therapeutic, beyond intestinal CRE infections and investigates its mechanism of action from a microbiome perspective. First, the genetic characteristics of the novel strain were identified through whole-genome analysis, and a scalable cultivation process was established as part of the overall development of this microbiome therapeutic. PMC101 increased the survival rate to 100%, significantly reduced disease severity scores, and prevented weight loss in CRE-infected mice treated with antibiotics. These effects are attributed to the inhibition of CRE growth in stool and the reduced detection of CRE in the lungs and kidneys, indicating suppression of systemic translocation. Metagenomic analysis revealed that PMC101 prevented the reduction in microbial population caused by antibiotics and CRE infection, restored species diversity indices, and mitigated dysbiosis while promoting eubiosis. This CRE translocation suppression was closely associated with increased CRE translocation-microbiome index, defined as the ratio of Bacteroidetes to Proteobacteria. This relationship was further confirmed through simulations using a human intestinal microbial ecosystem model. Additionally, increases in short-chain fatty acids, reductions in excessive inflammatory responses, and decreases in tissue damage were observed, all of which contribute to preventing CRE translocation. Finally, pathogen inhibition effects and safety tests were conducted, confirming the prophylactic potential of PMC101 as a microbiome therapeutic. These findings strongly support PMC101 as a promising candidate for future microbiome-based therapies against CRE infections.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"49"},"PeriodicalIF":3.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292776","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":"Pseudomonas fragi or not? Beyond MALDI-TOF in the frontier of Pseudomonas diversity.","authors":"María Guadalupe Martínez-Zavaleta, Rodolfo García-Contreras, Yuki Hoshiko, Toshinari Maeda, Nurhasliza Zolkefli, Claudia Adriana Colín-Castro, Melissa Hernández-Durán, Laura Aguilar-Vega, Jossue Ortíz-Álvarez, Rafael Franco-Cendejas, Luis Esaú López-Jácome","doi":"10.1007/s00430-025-00855-x","DOIUrl":"10.1007/s00430-025-00855-x","url":null,"abstract":"<p><p>Advanced platforms, such as whole genome sequencing (WGS), should be employed to enhance and refine microbial identification compared to phenotypic methods, including miniaturized biochemical tests and MALDI-TOF. The application of WGS has led to the reclassification of clinical bacterial pathogens previously misidentified by phenotypic techniques. In this study, eight clinical isolates initially identified as Pseudomonas fragi by VITEK MS were subjected to WGS and bioinformatics analysis. The results revealed one strain as Pseudomonas lundensis, while average nucleotide identity and phylogenetic reconstruction suggested that the remaining seven strains represent novel species within the Pseudomonas fluorescens superclade. The strains harbored four antimicrobial resistance genes conferring resistance to β-lactams, fluoroquinolones, phenicols, and tetracyclines, yet in vitro assays indicated susceptibility to carbapenems and intermediate susceptibility to colistin. Additionally, the strains possessed virulence factor genes associated with alginate biosynthesis, flagellar formation, pilus assembly, and iron uptake, with Type III Secretion System (T3SS)-related genes detected only in P. lundensis. Notably, the isolated Pseudomonas spp., exhibited multiple haplotypes, a closely related pan-genome, and similar phenotypic characteristics. These findings underscore the necessity of integrating multiple approaches, including molecular methods such as 16S rRNA gene amplification, sanger sequencing, and WGS, alongside traditional phenotypic techniques, to improve the accuracy of microbial identification in clinical settings.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"48"},"PeriodicalIF":3.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232986","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":"Characterizing tuberculous meningitis in a South African pediatric cohort using GCxGC-TOFMS metabolomics.","authors":"Anouska Mangaroo-Pillay, Du Toit Loots, Regan Solomons, Shayne Mason","doi":"10.1007/s00430-025-00857-9","DOIUrl":"10.1007/s00430-025-00857-9","url":null,"abstract":"<p><p>The objective of this study was to characterize the metabolic profile of tuberculous meningitis (TBM) in the cerebrospinal fluid (CSF) of a South African pediatric cohort using two-dimensional gas chromatography linked to time-of-flight mass spectrometry (GCxGC-TOFMS). A metabolite extraction and derivatization protocol was performed using CSF samples from 21 cases of bacteriologically confirmed TBM and 24 controls without meningitis, and analyzed by GCxGC-TOFMS, followed by univariate and multivariate statistical comparisons to identify differentiating compounds. A total of 48 metabolites (involved in glycolysis and amino acid and fatty acid metabolism) were identified that differentiated the two groups (effect size d-value > 0.5 and partial least squares discriminant analysis VIP value > 1.0, with 16 metabolites highlighted as significant (p-value < 0.05). Eight novel metabolites (linked to imines, alkenes, and volatile organic compounds), never before identified in a TBM study, characterize TBM in this cohort. This study confirms existing metabolomics research aimed at characterizing the metabolic profile of TBM. Some affected metabolic pathways include glycolysis, pentose phosphate pathway, amino acids, and fatty acid metabolism. New information is provided on the effect TBM has on neurometabolism, how TBM can reduce the neuroprotective function of some metabolites in the brain, resulting in the neurological symptoms typically associated with this disease, and contribute to our understanding of the pathogenesis of TBM; ultimately, contributing to the development of a metabolic model of TBM.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"46"},"PeriodicalIF":3.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176462","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":"Effect of controlled human Plasmodium falciparum infection on B cell subsets in individuals with different levels of malaria immunity.","authors":"Pilar Requena, Gloria Patricia Gómez-Pérez, Matthew B B McCall, Diana Barrios, Ruth Aguilar, Julia Fernández-Morata, Marta Vidal, Joseph J Campo, Carla Sanchez, Maria Yazdabankhsh, B Kim Lee Sim, Stephen L Hoffman, Peter Kremsner, Bertrand Lell, Benjamin Mordmüller, Carlota Dobaño, Gemma Moncunill","doi":"10.1007/s00430-025-00847-x","DOIUrl":"10.1007/s00430-025-00847-x","url":null,"abstract":"<p><p>Continuous exposure to Plasmodium falciparum (Pf) has been associated with alterations in B cells. We investigated the effect of controlled human malaria infection (CHMI) on B cell phenotypes in individuals with different Pf immunity status: malaria-naïve, immunized with PfSPZ-CVac and semi-immune (lifelong-exposed) volunteers. Compared to naïve, semi-immune but not vaccinated individuals, had increased baseline frequencies of immature B cells (CD19⁺CD10⁺), active naive (IgD⁺CD27^-CD21^-) B cells, active atypical (IgD^-CD27^-CD21^-) memory B cells (MBCs), active classical (IgD^-CD27⁺CD21^-) MBCs and CD1c⁺-B cells but lower frequencies of some IgG⁺-B cells. The frequencies of CD1c⁺ active atypical MBCs correlated positively with anti-Pf antibodies and negatively with circulating eotaxin levels, while the opposite was observed for IgG⁺ resting atypical MBCs. During early blood-stage infection (day 11 after CHMI), there was an expansion of resting classical (IgD^-CD27⁺CD21⁺) MBCs in all three groups. Vaccination, compared to placebo, altered the effect of CHMI on B cells, showing a positive association with resting classical MBCs (β = 0.190, 95% CI 0.011-0.368) and active naïve-PD1⁺ (β = 0.637, 95% CI 0.058 to 1.217) frequencies, and a negative one with CD1c⁺ resting atypical MBCs (β = - 0.328, 95% CI - 0.621 to - 0.032). In addition, the sickle cell trait in semi-immune subjects altered the effect of CHMI on several B cells. In conclusion, lifelong but not vaccine exposure to malaria was associated with increased frequencies of multiple B cell subsets, with higher and lower percentages of CD1c and IgG expressing-cells, respectively. A single infection (CHMI) induces changes in B cell frequencies and is modulated by sickle cell trait and malaria-immunity status.Clinical Trials Registration NCT01624961, NCT02115516, and NCT02237586.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"47"},"PeriodicalIF":3.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176383","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":"Diagnostic performance of circulating microRNA signatures for differentiating tuberculosis disease from tuberculosis infection.","authors":"Anne Ahrens Østergaard, Stephanie Bjerrum, Kristian Assing, Maria Bisgaard Borup, Rasmus Bank Lynggaard, Christiane Abildgaard, Ingrid Louise Titlestad, Torben Tranborg Jensen, Hans Johan Niklas Lorentsson, Ole Hilberg, Christian Morberg Wejse, Søren Feddersen, Isik Somuncu Johansen","doi":"10.1007/s00430-025-00853-z","DOIUrl":"10.1007/s00430-025-00853-z","url":null,"abstract":"<p><p>As regulators of innate and adaptive immunity, microRNAs (miRNAs) could aid in the discrimination between tuberculosis disease (TB) and (latent) TB infection (TBI). We analysed 754 circulating miRNAs in participants diagnosed with TB and TBI using TaqMan™ Advanced miRNA Human A and B cards. MiRNAs were normalized exogenously and endogenously via geometric means of selected reference miRNAs. Expression analysis was used to identify miRNAs that were significantly differentially expressed between individuals with TB and those with TBI. We utilised recursive feature elimination with a Random Forest model to identify the miRNAs most effective at discriminating TB from TBI and subsequently validated the miRNA in another group. 95 persons diagnosed with TB or TBI was divided into a discovery group (n = 36) and a validation group (n = 59). In the discovery group, we identified 495 distinct miRNAs in 36 persons with TB or TBI and by recursive feature elimination identified hsa-miR-148a-3p, hsa-miR-204-5p and hsa-miR-584-5p and created a three-miRNA-diagnostic model. In the validation group, the three-miRNA-diagnostic model had poorer performance. Expression analysis revealed 13 significantly differentially expressed miRNAs, including hsa-miR-148a-3p and hsa-miR-204-5p. Subsequent analysis in a validation group consisting of 59 persons revealed that six of the 14 miRNAs, including hsa-miR-148a-3p, exhibited the same pattern, albeit without statistical significance. Three circulating miRNAs showed potential for differentiating TB from TBI in the discovery cohort, but these differences were less pronounced in the validation cohort.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"45"},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131183","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":"Therapeutic potential of Bacillus sonorensis PMC204 membrane vesicles against drug-resistant Mycobacterium tuberculosis.","authors":"Youngkyoung Lee, Hoonhee Seo, Soyeon Lee, Dongsic Choi, Sukyung Kim, Md Abdur Rahim, Ho-Yeon Song","doi":"10.1007/s00430-025-00851-1","DOIUrl":"10.1007/s00430-025-00851-1","url":null,"abstract":"<p><p>Tuberculosis remains a severe global health threat, exacerbated by the rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis. Despite the urgent need for effective interventions, the development of anti-tuberculosis drugs has been slow, and the emergence of pan-drug-resistant strains underscores the critical need for innovative therapeutic strategies. This study introduces Bacillus sonorensis PMC204, a novel probiotic strain with potent anti-tuberculosis properties identified through extensive screening. PMC204 significantly reduced M. tuberculosis H37Rv and XDR strains within Raw 264.7 macrophage cells. Moreover, membrane vesicles (MVs) derived from this strain exhibited superior inhibitory effects against both standard and XDR strains of M. tuberculosis. Proteomic analysis of the isolated MVs revealed a high abundance of flagellin proteins, which are hypothesized to play a pivotal role in the observed anti-tuberculosis effects. These findings also suggest a close link between the therapeutic efficacy of PMC204 and autophagy activation. Safety assessments further demonstrated the feasibility of PMC204 as a potential anti-tuberculosis therapeutic. The anti-tuberculosis activity of bacterial MVs represents an innovative approach in microbiome therapeutics, positioning PMC204 as a next-generation probiotic distinct from conventional strains. This study contributes to advancing the field of microbiome-based therapeutics and presents promising avenues for managing drug-resistant tuberculosis.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"43"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086421","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}