Microbial pathogenesis最新文献

{"title":"Pairing antibiotics with phages: A new strategy to tackle biofilms of drug-resistant Acinetobacter baumannii—insights from in vitro and in vivo studies","authors":"Majid Taati Moghadam ,&nbsp;Mahsa Ziasistani ,&nbsp;Faeze Mahdiun ,&nbsp;Mohammad Hossein Sobhanipoor ,&nbsp;Massoumeh Ghasemi ,&nbsp;Elham Isaei ,&nbsp;Mahsa Kiaei","doi":"10.1016/j.micpath.2026.108290","DOIUrl":"10.1016/j.micpath.2026.108290","url":null,"abstract":"<div><div>Emerging multidrug-resistant (MDR) and extensively drug-resistant (XDR) <em>Acinetobacter baumanii</em> is a serious challenge in hospital settings. Biofilm formation is one of these bacteria's most crucial mechanisms of antibiotic resistance. Given the ineffectiveness of common antibiotics against MDR, XDR, and biofilm-forming <em>A. baumannii</em>, the healthcare system must use new strategies to combat <em>A. baumannii</em> biofilm. This study aimed to provide an overview of the in vitro, in vivo, and ex vivo combination therapy of phages and antibiotics for combating <em>A. baumanii</em> biofilms. Most studies suggest that pairing antibiotics with phages could help break down <em>A. baumannii</em> biofilms and treat infections caused by these hard-to-beat superbugs, especially when using cocktail phages and colistin to inhibit biofilm formation or eradicate biofilms. Many limitations of phage therapy can be overcome by combining phage therapy with antibiotics. Additionally, protein-derived phages have been proposed as a promising alternative or complementary approach to conventional therapies, demonstrating significant antibacterial activity. When used in combination with antibiotics, they may enhance treatment efficacy by reducing the spread of antibiotic-resistant <em>A. baumannii</em> and effectively eliminating their biofilms. Combining antibiotics with phage therapy may offer an effective strategy to disrupt <em>A. baumannii</em> biofilms in laboratory settings and improve treatment outcomes for patients with drug-resistant infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108290"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994438","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":"Mechanism of tea saponin in alleviating intestinal damage induced by E. coli infection via the NF-κB/NLRP3 pathway","authors":"Bo Zhang ,&nbsp;Bo Liao ,&nbsp;Fangjie Li ,&nbsp;Yanhong Lv ,&nbsp;Rong Liao ,&nbsp;Dengyao Xu ,&nbsp;Rou Sang ,&nbsp;Ke Li ,&nbsp;Aiguo Xin","doi":"10.1016/j.micpath.2026.108326","DOIUrl":"10.1016/j.micpath.2026.108326","url":null,"abstract":"<div><div>Pathogenic <em>Escherichia coli</em> is a common zoonotic pathogen that can cause host diarrhea, edema, and mortality. Tea saponin (Ts) exhibits significant anti-inflammatory and antioxidant properties. However, its potential to mitigate acute intestinal injury caused by pathogenic <em>E. coli</em> remains unclear. This research aimed to investigate the protective effects of Ts against inflammatory pathological damage induced by <em>E. coli</em> and to elucidate the underlying molecular mechanisms. Four experimental groups were established: control, <em>E. coli</em>, <em>E. coli</em> + Ts, and <em>E. coli</em> + MCC950 (a selective NLRP3 inhibitor). Inflammatory pathological damage in the mouse colon was assessed through HE staining, analysis of intestinal barrier markers (ZO-1, Occludin, and Claudin-1), ELISA of inflammatory factors, and analysis of oxidative stress markers. The expression of key apoptosis-related genes and NF-κB/NLRP3 pathway genes was detected using RT-PCR. Immunohistochemistry and Western blot were employed to analyze the expression of apoptosis-related proteins (Bcl-2 and Bax), activated forms of Caspases (Cleaved Caspase-1, Cleaved Caspase-3, Cleaved Caspase-8), tight junction proteins (ZO-1, Occludin, and Claudin-1), and NF-κB/NLRP3 pathway proteins in mouse colon tissues. <em>E. coli</em> infection induced severe histopathological changes and intestinal barrier dysfunction in colon tissues and activated the NF-κB/NLRP3 signaling pathway. This activation significantly increased the expression of pro-apoptotic genes Bax, Caspase-8, and Caspase-3, as well as the levels of their cleaved (active) forms, while markedly decreasing the expression of Bcl-2, thereby promoting apoptosis. Ts treatment notably ameliorated colon pathological injury, effectively regulated the expression of apoptosis-related genes, and significantly suppressed the transcription levels of NF-κB, NLRP3, Caspase-1, IL-1β, IL-18, and TNF-α within the NF-κB/NLRP3 signaling pathway. Furthermore, Ts treatment significantly reduced the protein levels of cleaved Caspase-1, cleaved Caspase-3, and cleaved Caspase-8, and restored the expression of ZO-1, Occludin, and Claudin-1. Ts effectively inhibits inflammatory responses and cell apoptosis induced by <em>E. coli</em> by modulating the NF-κB/NLRP3 signaling pathway, and maintaining intestinal barrier integrity via regulating tight junction proteins, ultimately alleviating colon damage in mouse.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108326"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081251","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":"Evaluating probiotic monotherapy in Helicobacter pylori infection: A meta-analysis of randomized controlled trials with trial sequential analysis","authors":"Vivek Mishra ,&nbsp;Debabrata Dash ,&nbsp;Aditya K. Panda ,&nbsp;Sushil Kumar Pathak","doi":"10.1016/j.micpath.2026.108316","DOIUrl":"10.1016/j.micpath.2026.108316","url":null,"abstract":"<div><h3>Background</h3><div>This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of probiotics in reducing <em>H. pylori</em> colonization in non-antibiotic interventions.</div></div><div><h3>Methods</h3><div>Systematic searches were conducted in PubMed, Scopus, Cochrane Library databases and Google Scholar. Data analysis was performed using CMA (V4) and Trial Sequential Analysis (TSA), with evidence certainty evaluated via GRADE.</div></div><div><h3>Results</h3><div>Twenty-eight studies met the inclusion criteria. Compared with placebo, probiotic monotherapy significantly reduced <em>H. pylori</em> colonization (RR = 1.712, 95 % CI: 1.240 to 2.364, I² = 37.80, p = 0.001), but total eradication was 16.8 %. Among the probiotic strains, <em>Lactobacillus reuteri</em> showed higher efficacy (event rate = 0.377, 95 % CI: 0.123 to 0.722, I² = 86.00). 4 weeks supplementation period yielded a stronger effect (event rate = 0.315, 95 % CI: 0.137 to 0.570, I² = 78.18). Changes in ¹³C-UBT values, indicating bacterial load reduction, were significant (SMD = −0.617, p &lt; 0.001, 95 % CI: −0.921 to −0.312, I² = 86.50), while gastrointestinal symptom relief scores showed moderate improvement (SMD = −0.253, p = 0.012, 95 % CI: −0.451 to −0.055, I² = 2.46). TSA validated that sufficient studies supported these findings, with evidence graded of moderate certainty.</div></div><div><h3>Conclusion</h3><div>While probiotic monotherapy, particularly <em>L. reuteri</em> appears to reduce <em>H. pylori</em> colonization and improve gastrointestinal symptoms, their effectiveness as a standalone therapy remains limited owing to low eradication rates and variability in study quality. Further well-designed trials are required to establish their optimal role, particularly as supportive or adjunctive interventions.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108316"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046683","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":"Virulence and antimicrobial resistance gene profiling in multidrug-resistant Pseudomonas aeruginosa with evaluation of levofloxacin and amikacin therapy","authors":"Sivaperumal Pitchiah ,&nbsp;Dhanraj Ganapathy ,&nbsp;Kannan Kamala","doi":"10.1016/j.micpath.2026.108334","DOIUrl":"10.1016/j.micpath.2026.108334","url":null,"abstract":"<div><div>Multidrug-resistant (MDR) <em>Pseudomonas aeruginosa</em> is an opportunistic pathogen responsible for severe oral and hospital-acquired infections due to its strong biofilm-forming ability and multidrug resistance (MDR). This study investigated the virulence and resistance of <em>P. aeruginosa</em> isolated from subgingival biofilms and evaluated the antibiofilm activity of levofloxacin (LVX) and amikacin (AMK), individually and in combination. From 157 subgingival samples, 14 isolates were confirmed as <em>P. aeruginosa</em>, all resistant to antibiotic classes, indicating MDR status. Susceptibility testing revealed complete resistance to amoxiclav (100 %) and high resistance to ceftazidime (85.7 %), with moderate resistance to ciprofloxacin and gentamicin. The isolate with the highest biofilm-forming ability was used for further analysis. Crystal violet quantification demonstrated that LVX and AMK inhibited biofilm biomass by 39.9 % and 59.9 % at 24 h and by 70 % and 75.1 % at 48 h, respectively, whereas their combination achieved 96.2 % inhibition at 48 h. Live cell inhibition assessed by acridine orange staining showed that the LVX–AMK combination resulted in 97 ± 1.2 % reduction of viable biofilm cells at 48 h (p &lt; 0.001). qRT-PCR analysis revealed 0.2–0.4-fold downregulation of virulence genes (<em>fadA, toxA, lasB, algD, exoS</em>) in the combination group. Structural modeling and Ramachandran analysis showed conserved and stable protein regions. These findings suggest that combined LVX–AMK therapy exhibits synergistic antibiofilm and anti-virulence effects against MDR <em>P. aeruginosa</em>, shows potential for treating biofilm-associated infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108334"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081252","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":"Exploring miRNAs in Leishmania infection: from immune modulation to theranostic potential","authors":"Hamzeh Sarvnaz ,&nbsp;Shima Hadifar ,&nbsp;Taha Masoudsinaki ,&nbsp;Hossein Heydari ,&nbsp;Ali M. Harandi ,&nbsp;Sima Rafati","doi":"10.1016/j.micpath.2026.108315","DOIUrl":"10.1016/j.micpath.2026.108315","url":null,"abstract":"<div><div>Leishmaniasis is a complex parasitic disease marked by intricate interactions between <em>Leishmania</em> parasites and host immune responses. Recent evidence has shown the importance of microRNAs (miRNAs), small non-coding RNAs, in the modulation of immunopathogenesis of leishmaniasis. This review synthesizes current understanding of miRNA biogenesis and their dynamic regulation during <em>Leishmania</em> infection. We detailed the mechanisms by which host-derived miRNAs modulate key signaling pathways, cytokine expression, and immune cell functions, thereby influencing disease progression and resolution. Notably, distinct miRNA expression profiles have been identified in infected hosts, correlating with parasite burden and clinical manifestations. Bioinformatic and experimental analyses highlighted various miRNA-mRNA interactions enriched in pathways such as TGF-β, JAK-STAT, MAPK, and NF-κB signaling, as well as antigen processing and presentation. Furthermore, the potential of miRNAs as diagnostic, prognostic, and therapeutic biomarkers in leishmaniasis is discussed. Taken together, this review discusses recent findings on the multifaceted roles of miRNAs in host–<em>Leishmania</em> interplay and highlights their promise as potential targets for innovative theranostic strategies.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108315"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040953","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":"Virulence and genomic features of hypervirulent Klebsiella pneumoniae species complex","authors":"Luis Duarte-Zambrano ,&nbsp;Neli Nava-Domínguez ,&nbsp;Christian Daniel Mireles-Dávalos ,&nbsp;Eduardo Becerril-Vargas ,&nbsp;Hilda Minerva González-Sánchez ,&nbsp;Nadia Rodríguez-Medina ,&nbsp;Jonathan Rodríguez-Santiago ,&nbsp;Elvira Garza-González ,&nbsp;Roberto Mercado-Longoria ,&nbsp;Luis Esaú López-Jácome ,&nbsp;Rayo Morfin-Otero ,&nbsp;Eduardo Rodríguez-Noriega ,&nbsp;Esteban Gonzalez-Diaz ,&nbsp;Maribel López-García ,&nbsp;Rocio Quinto-Manzanares ,&nbsp;Christian Sohlenkamp ,&nbsp;Alejandro Alvarado-Delgado ,&nbsp;Ulises Garza-Ramos","doi":"10.1016/j.micpath.2026.108305","DOIUrl":"10.1016/j.micpath.2026.108305","url":null,"abstract":"<div><div>Hypervirulent <em>Klebsiella pneumoniae</em> is a pathotype capable of causing invasive infections with high morbidity and mortality rates. In this study, we conducted a surveillance analysis of hypervirulent isolates circulating in Mexico to characterize their phenotypic and genomic features. Presumptive hypervirulent isolates were identified at a frequency of 6.48 % (19/293), comprising 17 <em>K. pneumoniae sensu stricto</em> and two <em>K. quasipneumoniae</em> subsp. <em>similipneumoniae</em>. Isolates were predominantly recovered from male patients (12/19, 63 %). Clinical samples were obtained from lower respiratory tract (15/19, 78.9 %), blood (3/19, 15.7 %), and pleural fluid (1/19, 5.2 %). Further genetic and phenotypic analyses revealed substantial heterogeneity among these strains, including significant phenotype-genotype discordance. Notably, this cohort includes the first identified convergent hypervirulent <em>K. pneumoniae</em> strain in Mexico, as well as two hypervirulent <em>K. quasipneumoniae</em> isolates, a phenomenon that is less frequent in <em>K.</em> <em>quasipneumoniae</em> than in <em>K. pneumoniae</em>. These discrepancies prompted us to propose a local classification scheme based on the presence of virulence-associated genes, lethality in mice and antimicrobial susceptibility. Phylogenetic and pangenome analysis revealed clustering patterns associated with sequence types and capsule serotypes. The data generated in this study contribute to a deeper understanding of Hypervirulent <em>K. pneumoniae</em> species complex biology and provide valuable insights into the diversity of strains currently circulating in Mexico.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108305"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046763","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":"Catechol-phytochemical conjugates potentiate quorum quenching and antivirulence response against Pseudomonas aeruginosa","authors":"Tamanna Dua ,&nbsp;Jatin Chadha ,&nbsp;Akshita Goel ,&nbsp;Purshotam Sharma ,&nbsp;Kusum Harjai ,&nbsp;Vasundhara Singh","doi":"10.1016/j.micpath.2026.108287","DOIUrl":"10.1016/j.micpath.2026.108287","url":null,"abstract":"<div><div>Development of drug hybrids with anti-quorum sensing (QS) and antivirulence properties has been widely regarded as a viable alternative for combating drug resistance in <em>Pseudomonas aeruginosa</em>. In this study, conjugates <strong>(1</strong>–<strong>3)</strong> were synthesized using three naturally-occurring phytochemicals: guaiacol, vanillin, and eugenol <em>via</em> pharmacophoric hybridization with catechol moiety. Among the synthesized conjugates that showed broad-spectrum antibacterial activity and iron-chelating potential, catechol-vanillin conjugate <strong>(2)</strong> demonstrated relatively higher degree of QS inhibition and significantly reduced AHL production (49.5 %) in <em>P. aeruginosa</em>. Although catechol-guaiacol <strong>(1)</strong> &amp; catechol-eugenol <strong>(3)</strong> conjugates drastically attenuated pseudomonal virulence, catechol-vanillin conjugate <strong>(2)</strong> showed maximum curtailment over hemolysin (42.8 %), pyocyanin (56.5 %), alginate (49.9 %), rhamnolipid (32.7 %) production and protease/elastase (39.1 %/68.8 %) activity alongside impeding motility phenotypes at sub-MIC levels. These findings were correlated with molecular docking studies that predicted strong interactions between catechol-vanillin conjugate <strong>(2)</strong> and PqsR receptor (−11.87 kcal mol⁻¹) of <em>P. aeruginosa</em>. Analytical TLC further confirmed a notable reduction in PQS production, thereby confirming that conjugate <strong>2</strong> extends antivirulence response <em>via</em> curtailment of Pqs pathway. Additionally, all the synthesized conjugates <strong>(1</strong>–<strong>3)</strong> exhibited a non-cytotoxic (biocompatible) nature towards sheep erythrocytes and HEK 293 cells <em>in vitro</em>, thereby paving way for pre-clinical validation of their antivirulence potential in animal models <em>in vivo</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108287"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933980","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":"Prim-O-glucosylcimifugin targets Staphylococcus aureus caseinolytic protease P to inhibit α-hemolysin expression and promote healing of MRSA-induced diabetic skin infections","authors":"Yan Wang,&nbsp;Shanshan Luo,&nbsp;Xinping Guo,&nbsp;Mengli Jin,&nbsp;Xingye Wang,&nbsp;Mingran Li,&nbsp;Shuang Jiang,&nbsp;Lin Wei,&nbsp;Mingjun Liu,&nbsp;Wu Song","doi":"10.1016/j.micpath.2026.108296","DOIUrl":"10.1016/j.micpath.2026.108296","url":null,"abstract":"<div><div>Targeting bacterial virulence factors is considered a promising strategy because it poses a lower risk of promoting antibiotic resistance. This study investigated the therapeutic potential and underlying mechanism of prim-O-glucosylcimifugin (POG) against <em>Staphylococcus aureus</em> (<em>S. aureus</em>). In a diabetic mouse model, POG significantly reduced bacterial burden and accelerated wound healing, which was accompanied by enhanced tissue regeneration and collagen deposition, but no detectable toxicity. It also improved survival in a <em>Galleria mellonella</em> model infected with methicillin-resistant <em>S. aureus</em>. <em>In vitro</em>, POG did not inhibit bacterial growth, indicating an antivirulence rather than bactericidal mode of action. Transcriptomic analysis revealed that POG downregulated multiple virulence-associated genes, including α-hemolysin (<em>hla</em>), and disrupted quorum sensing, stress response, and metabolic pathways. Consistently, POG treatment suppressed hemolytic activity and the production of Hla. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays confirmed the direct binding of POG to <em>S. aureus</em> caseinolytic protease P (SaClpP). Furthermore, fluorescence resonance energy transfer assays demonstrated that POG inhibited SaClpP activity in a dose-dependent manner, with an IC₅₀ of 14.27 μg/mL. In a clpP knockout strain, the suppressive effects of POG on Hla production and hemolytic activity were abolished, confirming SaClpP as the key target responsible for its antivirulence effects. Collectively, these results demonstrate that POG is a promising antivirulence agent that attenuates <em>S. aureus</em> pathogenicity by targeting SaClpP.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108296"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952442","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":"Marine Streptomyces-derived 2,4-di-tert-butylphenol enhances autophagy to eliminate mycobacteria in human macrophages","authors":"Salina Patel ,&nbsp;Shivananda Behera ,&nbsp;Lincoln Naik ,&nbsp;Mousumi Das ,&nbsp;Dev Kiran Nayak ,&nbsp;Pramathesh Kumar Dandsena ,&nbsp;Mustafeez Ali Quaderi ,&nbsp;Amit Mishra ,&nbsp;Ramandeep Singh ,&nbsp;Surajit Das ,&nbsp;Rohan Dhiman","doi":"10.1016/j.micpath.2026.108297","DOIUrl":"10.1016/j.micpath.2026.108297","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>M. tb</em>), the causative agent of tuberculosis (TB), remains a major global health threat, highlighting the need for novel therapeutic strategies. Host-directed therapies (HDTs), particularly autophagy induction via natural or pharmacological agents, offer promising strategies for combating mycobacteria. This study assessed the anti-mycobacterial potential of marine-derived <em>Streptomyces</em> spp. Briefly, the isolated marine <em>Streptomyces</em> spp. underwent primary and secondary screenings to assess their inhibitory activity against <em>M. smegmatis</em>. Notably, the cell-free extract of <em>Streptomyces fradiae</em> DNS4 (<em>S. fradiae</em> DNS4) demonstrated the most vigorous anti-mycobacterial activity. Optimization of culture conditions revealed maximal secondary metabolite production in ISP-7 medium at 28°C and pH 7 by <em>S. fradiae</em> DNS4. Furthermore, extraction using ethyl acetate, followed by GC-MS analysis, identified seventeen compounds, including the potent anti-mycobacterial secondary metabolite 2,4-di-tert-butylphenol [2,4-(DTBP)]. Subsequent experiments evaluated the host-directed anti-mycobacterial mechanism of action for 2,4-(DTBP) using dTHP-1 cells. At a non-cytotoxic concentration (10 μM), 2,4-(DTBP) treatment markedly reduced intracellular mycobacterial survival compared to untreated controls. Multiparametric investigations into autophagy induction, including LC3-I to LC3-II conversion, protein expression profiling of key autophagy markers, and MDC staining, demonstrated enhanced autophagic responses in 2,4-(DTBP)-treated macrophages. Upon 2,4-(DTBP) treatment, enhanced autophagic flux was further confirmed by increased LC3-II accumulation under Baf-A1 pre-treatment conditions. Importantly, autophagy inhibition by pre-treatment with 3-MA abolished the observed anti-mycobacterial effects, confirming the specific autophagy-dependent mechanism of 2,4-(DTBP). Collectively, these findings highlight the potential of marine-derived 2,4-(DTBP) from <em>S. fradiae</em> DNS4 as a novel host-directed anti-mycobacterial agent, which is mediated primarily through the targeted augmentation of autophagy in human macrophages.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108297"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959636","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":"Fecal microbiota transplantation attenuates neuropathic pain in rats via gut microbiota-mediated immunomodulation of ion channels and nociceptors","authors":"Meghana Allani ,&nbsp;Gopal Nath ,&nbsp;Garima Juyal ,&nbsp;Mohan Chandra Joshi ,&nbsp;Vinod Tiwari","doi":"10.1016/j.micpath.2026.108275","DOIUrl":"10.1016/j.micpath.2026.108275","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuropathic pain, resulting from somatosensory nervous system damage, presents significant treatment challenges due to limited effectiveness and adverse side effects of current therapies. Emerging evidence highlights the gut microbiome's potential role in pain regulation, yet the specific microbial species and mechanisms underlying chronic neuropathic pain remain largely unexplored.</div></div><div><h3>Objectives</h3><div>This study aimed to determine the relationship between gut microbiota and neuropathic pain using fecal microbiota transplantation (FMT) in rats with chronic constriction injury (CCI). Additionally, it sought to identify microbial species associated with pain modulation.</div></div><div><h3>Methods</h3><div>CCI was performed in <em>wildtype</em> and antibiotic-treated pseudo-germ-free (PGF) rats. FMT was performed using fecal matter slurry from healthy (hFMT) and CCI-dysbiotic (dFMT) donors, transplanted into nerve-injured and healthy rats, respectively. Pain-related behaviors were assessed and microbial composition was analyzed via 16sRNA sequencing. Western blot and RT-PCR assays were conducted on dorsal root ganglion (DRG) and spinal cord tissues.</div></div><div><h3>Results</h3><div>CCI induced gut microbial dysbiosis, characterized by increased <em>Proteobacteria</em> and <em>Fusobacteriota</em> and decreased <em>Actinobacteria</em>. hFMT from healthy rats alleviated mechanical, thermal, and cold hyperalgesia but did not reverse mechanical allodynia in CCI rats. Conversely, dFMT from CCI rats induced pain-like hypersensitivity in healthy rats, mimicking nerve injury effects. Correlation analysis identified microbial species linked to pain modulation: <em>Bifidobacterium animalis</em>, <em>Corynebacterium urealyticum,</em> and <em>Desulfovibrio piger</em> were associated with reduced pain behaviors, while <em>Pasteurellaceae bacterium</em>, <em>Bacillus sp</em>., and <em>Staphylococcus arlettae</em> were linked to nerve injury-induced dysbiosis. hFMT restored claudin-5 and anti-inflammatory markers TGF-β and IL-10 while downregulating pain-related proteins TRPM8, Nav 1.8, Nav 1.7, and TRPA1 in CCI rats. In contrast, dFMT promoted neuroinflammation by increasing IBA1, TNF-α, and IL-1β, leading to microglial activation in healthy rats.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that the composition of gut bacteria influences pain-like behaviors through nerve injury-induced microbial dysbiosis, operating in a bidirectional manner. Additionally, the study suggests that a cocktail of <em>Bifidobacterium animalis</em>, <em>Corynebacterium urealyticum</em>, and <em>Desulfovibrio piger</em> could serve as a promising alternative for managing neuropathic pain.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108275"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900750","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}