Bacterial diarrhea involves colonic water absorption dysfunction and gut microbiota disruption. Gegen Qinlian decoction (GQD) is clinically used to treat infectious diarrhea, yet its mechanisms remain incompletely understood. This study aimed to investigate how GQD modulates gut microbiota and enhances colonic water absorption in E. coli-induced diarrhea. Using an E. coli-induced piglet diarrhea model together with a rat colonic perfusion model, results show that GQD alleviates diarrhea-associated intestinal injury and inflammation and improves colonic water absorption. Mechanistically, GQD was associated with increased colonic aquaporin-3 (AQP3) expression and attenuation of the cAMP-protein kinase A-cystic fibrosis transmembrane conductance regulator (cAMP-PKA-CFTR) secretory signaling axis. 16S rRNA sequencing indicated enrichment of Lactobacillus amylovorus after GQD treatment, and administration of L. amylovorus partially reproduced the anti-diarrheal phenotype and transport-related signaling changes. In vitro assays further suggested that GQD suppresses E. coli growth while promoting L. amylovorus metabolic activity, and molecular docking provided hypothesis-generating predictions of candidate phytochemicals and bacterial targets. Overall, GQD may improve bacterial dysbiosis by enriching L. amylovorus and inhibiting E. coli, thereby restoring colonic water transport via the cAMP/CFTR/AQP3 pathway and ultimately improving bacterial diarrhea.
{"title":"Gegen Qinlian decoction alleviates bacterial diarrhea via Lactobacillus amylovorus-modulated restoration of colonic water transport through the cAMP/CFTR/AQP3 pathway.","authors":"Zhen-Ye Luo, Zhe Chen, Feng-Lin Zhang, Chang-Shun Liu, Fei-Long Chen, Ze-Zhong Zheng, Xiao-Mei Tan","doi":"10.1016/j.micpath.2026.108434","DOIUrl":"10.1016/j.micpath.2026.108434","url":null,"abstract":"<p><p>Bacterial diarrhea involves colonic water absorption dysfunction and gut microbiota disruption. Gegen Qinlian decoction (GQD) is clinically used to treat infectious diarrhea, yet its mechanisms remain incompletely understood. This study aimed to investigate how GQD modulates gut microbiota and enhances colonic water absorption in E. coli-induced diarrhea. Using an E. coli-induced piglet diarrhea model together with a rat colonic perfusion model, results show that GQD alleviates diarrhea-associated intestinal injury and inflammation and improves colonic water absorption. Mechanistically, GQD was associated with increased colonic aquaporin-3 (AQP3) expression and attenuation of the cAMP-protein kinase A-cystic fibrosis transmembrane conductance regulator (cAMP-PKA-CFTR) secretory signaling axis. 16S rRNA sequencing indicated enrichment of Lactobacillus amylovorus after GQD treatment, and administration of L. amylovorus partially reproduced the anti-diarrheal phenotype and transport-related signaling changes. In vitro assays further suggested that GQD suppresses E. coli growth while promoting L. amylovorus metabolic activity, and molecular docking provided hypothesis-generating predictions of candidate phytochemicals and bacterial targets. Overall, GQD may improve bacterial dysbiosis by enriching L. amylovorus and inhibiting E. coli, thereby restoring colonic water transport via the cAMP/CFTR/AQP3 pathway and ultimately improving bacterial diarrhea.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108434"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390205","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":"Corrigendum to \"Targeted inhibition of Candida albicans by red alga Palisada cruciata (Harvey) K.W. Nam (2007): A new report on anticandidal and antioxidant potential with phytochemical analysis using GC-MS and FT-IR study\" [Microbial Pathogenesis 206 (2025) 107852].","authors":"Vigneshkumar Venkatesan, Antony Prakash Rejoy Patrick, Nagaraj Subramani","doi":"10.1016/j.micpath.2026.108425","DOIUrl":"10.1016/j.micpath.2026.108425","url":null,"abstract":"","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108425"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378192","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}
Emerging multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumanii 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 A. baumannii, the healthcare system must use new strategies to combat A. baumannii 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 A. baumanii biofilms. Most studies suggest that pairing antibiotics with phages could help break down A. baumannii 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 A. baumannii and effectively eliminating their biofilms. Combining antibiotics with phage therapy may offer an effective strategy to disrupt A. baumannii biofilms in laboratory settings and improve treatment outcomes for patients with drug-resistant infections.
{"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 , Mahsa Ziasistani , Faeze Mahdiun , Mohammad Hossein Sobhanipoor , Massoumeh Ghasemi , Elham Isaei , 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}
Pub Date : 2026-04-01Epub Date: 2026-01-26DOI: 10.1016/j.micpath.2026.108326
Bo Zhang , Bo Liao , Fangjie Li , Yanhong Lv , Rong Liao , Dengyao Xu , Rou Sang , Ke Li , Aiguo Xin
Pathogenic Escherichia coli 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 E. coli remains unclear. This research aimed to investigate the protective effects of Ts against inflammatory pathological damage induced by E. coli and to elucidate the underlying molecular mechanisms. Four experimental groups were established: control, E. coli, E. coli + Ts, and E. coli + 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. E. coli 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 E. coli by modulating the NF-κB/NLRP3 signaling pathway, and maintaining intestinal barrier integrity via regulating tight junction proteins, ultimately alleviating colon damage in mouse.
{"title":"Mechanism of tea saponin in alleviating intestinal damage induced by E. coli infection via the NF-κB/NLRP3 pathway","authors":"Bo Zhang , Bo Liao , Fangjie Li , Yanhong Lv , Rong Liao , Dengyao Xu , Rou Sang , Ke Li , 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}
Pub Date : 2026-04-01Epub Date: 2026-01-23DOI: 10.1016/j.micpath.2026.108316
Vivek Mishra , Debabrata Dash , Aditya K. Panda , Sushil Kumar Pathak
Background
This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of probiotics in reducing H. pylori colonization in non-antibiotic interventions.
Methods
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.
Results
Twenty-eight studies met the inclusion criteria. Compared with placebo, probiotic monotherapy significantly reduced H. pylori 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, Lactobacillus reuteri 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 < 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.
Conclusion
While probiotic monotherapy, particularly L. reuteri appears to reduce H. pylori 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.
{"title":"Evaluating probiotic monotherapy in Helicobacter pylori infection: A meta-analysis of randomized controlled trials with trial sequential analysis","authors":"Vivek Mishra , Debabrata Dash , Aditya K. Panda , 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, I<sup>2</sup> = 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, I<sup>2</sup> = 86.00). 4 weeks supplementation period yielded a stronger effect (event rate = 0.315, 95 % CI: 0.137 to 0.570, I<sup>2</sup> = 78.18). Changes in <sup>13</sup>C-UBT values, indicating bacterial load reduction, were significant (SMD = −0.617, p < 0.001, 95 % CI: −0.921 to −0.312, I<sup>2</sup> = 86.50), while gastrointestinal symptom relief scores showed moderate improvement (SMD = −0.253, p = 0.012, 95 % CI: −0.451 to −0.055, I<sup>2</sup> = 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}
Multidrug-resistant (MDR) Pseudomonas aeruginosa 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 P. aeruginosa 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 P. aeruginosa, 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 < 0.001). qRT-PCR analysis revealed 0.2–0.4-fold downregulation of virulence genes (fadA, toxA, lasB, algD, exoS) 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 P. aeruginosa, shows potential for treating biofilm-associated infections.
{"title":"Virulence and antimicrobial resistance gene profiling in multidrug-resistant Pseudomonas aeruginosa with evaluation of levofloxacin and amikacin therapy","authors":"Sivaperumal Pitchiah , Dhanraj Ganapathy , 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 < 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}
Pub Date : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.micpath.2026.108315
Hamzeh Sarvnaz , Shima Hadifar , Taha Masoudsinaki , Hossein Heydari , Ali M. Harandi , Sima Rafati
Leishmaniasis is a complex parasitic disease marked by intricate interactions between Leishmania 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 Leishmania 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–Leishmania interplay and highlights their promise as potential targets for innovative theranostic strategies.
{"title":"Exploring miRNAs in Leishmania infection: from immune modulation to theranostic potential","authors":"Hamzeh Sarvnaz , Shima Hadifar , Taha Masoudsinaki , Hossein Heydari , Ali M. Harandi , 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}
Pub Date : 2026-04-01Epub Date: 2026-01-23DOI: 10.1016/j.micpath.2026.108305
Luis Duarte-Zambrano , Neli Nava-Domínguez , Christian Daniel Mireles-Dávalos , Eduardo Becerril-Vargas , Hilda Minerva González-Sánchez , Nadia Rodríguez-Medina , Jonathan Rodríguez-Santiago , Elvira Garza-González , Roberto Mercado-Longoria , Luis Esaú López-Jácome , Rayo Morfin-Otero , Eduardo Rodríguez-Noriega , Esteban Gonzalez-Diaz , Maribel López-García , Rocio Quinto-Manzanares , Christian Sohlenkamp , Alejandro Alvarado-Delgado , Ulises Garza-Ramos
Hypervirulent Klebsiella pneumoniae 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 K. pneumoniae sensu stricto and two K. quasipneumoniae subsp. similipneumoniae. 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 K. pneumoniae strain in Mexico, as well as two hypervirulent K. quasipneumoniae isolates, a phenomenon that is less frequent in K.quasipneumoniae than in K. pneumoniae. 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 K. pneumoniae species complex biology and provide valuable insights into the diversity of strains currently circulating in Mexico.
{"title":"Virulence and genomic features of hypervirulent Klebsiella pneumoniae species complex","authors":"Luis Duarte-Zambrano , Neli Nava-Domínguez , Christian Daniel Mireles-Dávalos , Eduardo Becerril-Vargas , Hilda Minerva González-Sánchez , Nadia Rodríguez-Medina , Jonathan Rodríguez-Santiago , Elvira Garza-González , Roberto Mercado-Longoria , Luis Esaú López-Jácome , Rayo Morfin-Otero , Eduardo Rodríguez-Noriega , Esteban Gonzalez-Diaz , Maribel López-García , Rocio Quinto-Manzanares , Christian Sohlenkamp , Alejandro Alvarado-Delgado , 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}
Pub Date : 2026-03-23DOI: 10.1016/j.micpath.2026.108441
Yuxuan Mou, Yi Liang, Dongyu Zhu, Menglei Wang, Yongjie Liu, Daxin Peng, Jianjun Dai, Min Jiang, Xiangkai Zhuge
Avian pathogenic Escherichia coli (APEC) is an important bacterial pathogen that causes systemic disease in poultry. Extracellular vesicles (EVs) released by APEC are involved in host-pathogen interactions, but the virulence factors they carry and their effects on avian immune cells are not fully understood. In this study, we examined whether the hemolysin variant HlyE (HlyE-V) is secreted via APEC EVs and evaluated its effects in chicken macrophage HD11 cells. EVs were isolated from the wild-type strain CBE59, the hlyE-V deletion mutant CBE59ΔhlyE-V, and the complemented strain CBE59CΔhlyE-V. EVs from all strains exhibited comparable particle sizes and protein concentrations. HlyE-V was detected in EVs from the wild-type and complemented strains but was absent from EVs of the mutant strain. EVs from all strains were internalized by HD11 cells, while only EVs carrying HlyE-V induced pronounced cytotoxicity and apoptosis. Treatment with APEC EVs increased the transcription levels of Bax, Caspase-3, and Caspase-9 and reduced Bcl-2 levels, indicating the activation of intrinsic, mitochondria-dependent apoptosis. Although EVs also upregulated the transcription levels of TLR4 and MyD88, the hlyE-V deletion did not affected this pathway. Together, these findings demonstrate that APEC EVs carry HlyE-V, thereby enhancing EV-mediated cytotoxicity and intrinsic apoptosis in HD11 cells. This study identifies HlyE-V as an EV-associated virulence factor that contributes to the interaction between APEC and HD11 chicken macrophages.
{"title":"Extracellular Vesicles (EVs) Carrying Hemolysin HlyE Variant (HlyE-V) from Avian Pathogenic Escherichia coli (APEC) Induce Mitochondria-dependent Apoptosis in HD11 Macrophages.","authors":"Yuxuan Mou, Yi Liang, Dongyu Zhu, Menglei Wang, Yongjie Liu, Daxin Peng, Jianjun Dai, Min Jiang, Xiangkai Zhuge","doi":"10.1016/j.micpath.2026.108441","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108441","url":null,"abstract":"<p><p>Avian pathogenic Escherichia coli (APEC) is an important bacterial pathogen that causes systemic disease in poultry. Extracellular vesicles (EVs) released by APEC are involved in host-pathogen interactions, but the virulence factors they carry and their effects on avian immune cells are not fully understood. In this study, we examined whether the hemolysin variant HlyE (HlyE-V) is secreted via APEC EVs and evaluated its effects in chicken macrophage HD11 cells. EVs were isolated from the wild-type strain CBE59, the hlyE-V deletion mutant CBE59ΔhlyE-V, and the complemented strain CBE59CΔhlyE-V. EVs from all strains exhibited comparable particle sizes and protein concentrations. HlyE-V was detected in EVs from the wild-type and complemented strains but was absent from EVs of the mutant strain. EVs from all strains were internalized by HD11 cells, while only EVs carrying HlyE-V induced pronounced cytotoxicity and apoptosis. Treatment with APEC EVs increased the transcription levels of Bax, Caspase-3, and Caspase-9 and reduced Bcl-2 levels, indicating the activation of intrinsic, mitochondria-dependent apoptosis. Although EVs also upregulated the transcription levels of TLR4 and MyD88, the hlyE-V deletion did not affected this pathway. Together, these findings demonstrate that APEC EVs carry HlyE-V, thereby enhancing EV-mediated cytotoxicity and intrinsic apoptosis in HD11 cells. This study identifies HlyE-V as an EV-associated virulence factor that contributes to the interaction between APEC and HD11 chicken macrophages.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108441"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513293","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}
Pub Date : 2026-03-23DOI: 10.1016/j.micpath.2026.108458
Jong-Hun Ha, Kyu-Min Kim, Jin-Sik Park, Dong-Chul Kim, Hyung-Lyun Kang, Seung-Chul Baik, Myunghwan Jung, Hyun-Eui Park, Min-Kyoung Shin, Woo-Kon Lee
Low dietary intake of vitamin C (ascorbic acid) has been associated with unfavorable clinical outcomes of Helicobacter pylori infection in human studies. However, experimental evidence regarding the influence of host vitamin C status on H. pylori colonization remains inconsistent across animal models. In this study, we generated vitamin C-deficient L-gulono-γ-lactone oxidase-deficient (gulo-/-) mice on an FVB genetic background to evaluate host susceptibility to H. pylori infection under defined vitamin C supplementation conditions. FVB gulo-/- mice were orally infected with H. pylori and provided drinking water containing either low (330 mg/L) or high (3,300 mg/L) concentrations of vitamin C. Gastric colonization levels were assessed at 16 and 32 weeks post-infection (WPI). At 16 WPI, H. pylori colonization was significantly higher in gulo-/- mice receiving low-dose vitamin C compared with those receiving high-dose supplementation (p = 0.007) and wild-type mice (p = 0.03). Histopathological analysis revealed increased lymphocytic infiltration in the gastric mucosa of gulo-/- mice receiving low-dose vitamin C during chronic infection, whereas minimal inflammatory changes were observed in mice receiving high-dose vitamin C. These findings demonstrate that vitamin C deficiency influences H. pylori colonization and gastric pathology in a host genetic background-dependent manner. The FVB gulo-/- mouse model provides a useful experimental platform for investigating host factors that modulate H. pylori infection and disease progression.
{"title":"Vitamin C-Deficient Gulo<sup>-</sup>/<sup>-</sup> Mice Exhibit Increased Susceptibility to Helicobacter pylori Colonization and Gastric Pathology.","authors":"Jong-Hun Ha, Kyu-Min Kim, Jin-Sik Park, Dong-Chul Kim, Hyung-Lyun Kang, Seung-Chul Baik, Myunghwan Jung, Hyun-Eui Park, Min-Kyoung Shin, Woo-Kon Lee","doi":"10.1016/j.micpath.2026.108458","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108458","url":null,"abstract":"<p><p>Low dietary intake of vitamin C (ascorbic acid) has been associated with unfavorable clinical outcomes of Helicobacter pylori infection in human studies. However, experimental evidence regarding the influence of host vitamin C status on H. pylori colonization remains inconsistent across animal models. In this study, we generated vitamin C-deficient L-gulono-γ-lactone oxidase-deficient (gulo<sup>-/-</sup>) mice on an FVB genetic background to evaluate host susceptibility to H. pylori infection under defined vitamin C supplementation conditions. FVB gulo<sup>-/-</sup> mice were orally infected with H. pylori and provided drinking water containing either low (330 mg/L) or high (3,300 mg/L) concentrations of vitamin C. Gastric colonization levels were assessed at 16 and 32 weeks post-infection (WPI). At 16 WPI, H. pylori colonization was significantly higher in gulo<sup>-/-</sup> mice receiving low-dose vitamin C compared with those receiving high-dose supplementation (p = 0.007) and wild-type mice (p = 0.03). Histopathological analysis revealed increased lymphocytic infiltration in the gastric mucosa of gulo<sup>-/-</sup> mice receiving low-dose vitamin C during chronic infection, whereas minimal inflammatory changes were observed in mice receiving high-dose vitamin C. These findings demonstrate that vitamin C deficiency influences H. pylori colonization and gastric pathology in a host genetic background-dependent manner. The FVB gulo<sup>-/-</sup> mouse model provides a useful experimental platform for investigating host factors that modulate H. pylori infection and disease progression.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108458"},"PeriodicalIF":3.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513307","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}
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