Pub Date : 2026-01-23DOI: 10.1016/j.micpath.2026.108323
Miquel Sánchez-Osuna, Marc Bravo, María-Alexandra Cañas, Andrómeda-Celeste Gómez, Inmaculada Gómez-Sánchez, José M Miró, Isidre Gibert, Oriol Gasch, Cristina García-de-la-Mària, Daniel Yero, Oscar Q Pich
Staphylococcus aureus is a major human pathogen responsible for severe infections, including infective endocarditis. While host factors influencing disease outcome are well characterized, lineage-specific virulence mechanisms remain poorly defined. Herein, we investigated eighty-nine bacteremic S. aureus isolates from nine globally distributed lineages using Galleria mellonella and rabbit infection models, alongside phenotypic and transcriptomic analyses. Despite marked genotypic and phenotypic heterogeneity, mortality in G. mellonella varied significantly between lineages and correlated with hemolytic activity. ST398 isolates demonstrated heightened larval virulence linked to increased α- and δ-hemolysin production, whereas CC30 strains exhibited reduced growth, biofilm formation and infectivity. The ST398 agrC mutant Sau7 displayed a distinct phenotype, with elevated biofilm production but attenuated larval virulence. However, in the rabbit endocarditis model, Sau7 exhibited mortality rates similar to other ST398 isolates and was associated with larger vegetations and higher bacterial burdens, underscoring the role of the agr system in colonization and biofilm development. Transcriptomic profiling highlighted quorum-sensing pathways and hemolysin expression as key drivers of virulence in ST398 strains. Our findings reveal clear lineage-specific differences in S. aureus pathogenicity and demonstrate that virulence is context dependent, varying across infection models. These results emphasize the importance of using complementary in vivo systems to capture the multifaceted nature of S. aureus disease potential and to better predict infection outcomes.
{"title":"Comparative mortality of dominant Staphylococcus aureus lineages in human bacteremia and animal infection models.","authors":"Miquel Sánchez-Osuna, Marc Bravo, María-Alexandra Cañas, Andrómeda-Celeste Gómez, Inmaculada Gómez-Sánchez, José M Miró, Isidre Gibert, Oriol Gasch, Cristina García-de-la-Mària, Daniel Yero, Oscar Q Pich","doi":"10.1016/j.micpath.2026.108323","DOIUrl":"10.1016/j.micpath.2026.108323","url":null,"abstract":"<p><p>Staphylococcus aureus is a major human pathogen responsible for severe infections, including infective endocarditis. While host factors influencing disease outcome are well characterized, lineage-specific virulence mechanisms remain poorly defined. Herein, we investigated eighty-nine bacteremic S. aureus isolates from nine globally distributed lineages using Galleria mellonella and rabbit infection models, alongside phenotypic and transcriptomic analyses. Despite marked genotypic and phenotypic heterogeneity, mortality in G. mellonella varied significantly between lineages and correlated with hemolytic activity. ST398 isolates demonstrated heightened larval virulence linked to increased α- and δ-hemolysin production, whereas CC30 strains exhibited reduced growth, biofilm formation and infectivity. The ST398 agrC mutant Sau7 displayed a distinct phenotype, with elevated biofilm production but attenuated larval virulence. However, in the rabbit endocarditis model, Sau7 exhibited mortality rates similar to other ST398 isolates and was associated with larger vegetations and higher bacterial burdens, underscoring the role of the agr system in colonization and biofilm development. Transcriptomic profiling highlighted quorum-sensing pathways and hemolysin expression as key drivers of virulence in ST398 strains. Our findings reveal clear lineage-specific differences in S. aureus pathogenicity and demonstrate that virulence is context dependent, varying across infection models. These results emphasize the importance of using complementary in vivo systems to capture the multifaceted nature of S. aureus disease potential and to better predict infection outcomes.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108323"},"PeriodicalIF":3.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046678","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 : 2026-01-23DOI: 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":"2026-01-23","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}
Pub Date : 2026-01-23DOI: 10.1016/j.micpath.2026.108318
Sijia Li , Liming Zhang , Xiaoqin Wang
Visceral leishmaniasis (VL) remains one of the most challenging parasitic diseases globally, with significant morbidity and mortality rates, particularly in endemic regions. First-line treatment regimens such as monochemotherapy with pentavalent antimonials, miltefosine, and amphotericin B are often hindered by toxicity, high cost, and the emergence of drug resistance. Recent advances in pharmacological interventions have expanded the therapeutic landscape to include synergistic drug combinations, novel synthetic compounds, and bioactive natural alternatives. This review critically examines the current pharmacological strategies for VL, emphasizing monochemotherapy, synergistic drug combinations, and the potential of novel chemical synthesis and natural products. The limitations of existing treatments, including adverse effects and drug resistance, are discussed, alongside emerging trends in drug development. By integrating these diverse therapeutic strategies, this review aims to provide a comprehensive understanding of current and emerging treatments for VL, highlighting the need for continued innovation to combat drug resistance and improve patient outcomes.
{"title":"Current and emerging pharmacological treatments for visceral leishmaniasis","authors":"Sijia Li , Liming Zhang , Xiaoqin Wang","doi":"10.1016/j.micpath.2026.108318","DOIUrl":"10.1016/j.micpath.2026.108318","url":null,"abstract":"<div><div>Visceral leishmaniasis (VL) remains one of the most challenging parasitic diseases globally, with significant morbidity and mortality rates, particularly in endemic regions. First-line treatment regimens such as monochemotherapy with pentavalent antimonials, miltefosine, and amphotericin B are often hindered by toxicity, high cost, and the emergence of drug resistance. Recent advances in pharmacological interventions have expanded the therapeutic landscape to include synergistic drug combinations, novel synthetic compounds, and bioactive natural alternatives. This review critically examines the current pharmacological strategies for VL, emphasizing monochemotherapy, synergistic drug combinations, and the potential of novel chemical synthesis and natural products. The limitations of existing treatments, including adverse effects and drug resistance, are discussed, alongside emerging trends in drug development. By integrating these diverse therapeutic strategies, this review aims to provide a comprehensive understanding of current and emerging treatments for VL, highlighting the need for continued innovation to combat drug resistance and improve patient outcomes.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108318"},"PeriodicalIF":3.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044292","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 : 2026-01-23DOI: 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":"2026-01-23","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 : 2026-01-22DOI: 10.1016/j.micpath.2026.108309
Anpeng Liu , Ling Xiao , Qianwen He , Zujin Xu, Yali Zhu, Zongze Zhang, Jia Zhan, Zhen Li
The primary focus of sepsis therapy is to alleviate organ dysfunction. Sepsis-associated liver injury (SALI) occurs in about 40 % of sepsis patients, yet targeted therapeutic strategies remain unavailable. Electroacupuncture (EA) has emerged as a potential adjunctive therapy for sepsis, owing to its capacity to modulate the neuroendocrine-immune network. This study aims to investigate whether EA can alleviate SALI and its potential mechanisms. A murine model of sepsis was established via cecal ligation and puncture (CLP). The Zusanli (ST36) and Neiguan (PC6) acupoints, known for their anti-inflammatory properties, were selected for EA intervention. Following CLP, mice received EA stimulation at ST36 and PC6 for 20 min daily over two consecutive days. The results showed that EA significantly improved survival and attenuated SALI. Transcriptomic profiling via mRNA-seq uncovered immune cell gene expression changes in response to EA. Bioinformatics analysis indicated that EA downregulated genes involved in proinflammatory responses and leukocyte migration, which were enriched in Toll-like receptors and NOD-like receptors signaling pathways. Further research confirmed that EA significantly reduced serum levels of the proinflammatory cytokines IL-6, TNF-α, and IL-1β in septic mice. Mechanistically, EA suppressed activation of the proinflammatory signaling pathway IκBα/NF-κB and concurrently attenuated pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD axis in immune cells.
脓毒症治疗的主要重点是减轻器官功能障碍。脓毒症相关肝损伤（SALI）发生在约40%的脓毒症患者中，但靶向治疗策略仍不可用。电针（EA）已成为一种潜在的辅助治疗败血症，由于其调节神经内分泌免疫网络的能力。本研究旨在探讨EA是否可以缓解SALI及其可能的机制。采用盲肠结扎穿刺法（CLP）建立小鼠脓毒症模型。选择具有抗炎作用的足三里（ST36）和内关（PC6）穴位进行EA干预。CLP后，小鼠在ST36和PC6处接受EA刺激，每天20分钟，连续2天。结果显示，EA可显著提高生存率，减轻SALI。通过mRNA-seq转录组学分析揭示了EA对免疫细胞基因表达的影响。生物信息学分析表明，EA下调了参与促炎反应和白细胞迁移的基因，这些基因在toll样受体和nod样受体信号通路中富集。进一步研究证实，EA可显著降低脓毒症小鼠血清中促炎因子IL-6、TNF-α和IL-1β的水平。在机制上，EA通过抑制免疫细胞的NLRP3/caspase-1/GSDMD轴，抑制促炎信号通路i - b α/NF-κB的激活，同时减轻焦亡。
{"title":"EA mitigates sepsis-induced liver injury by inhibiting the proinflammatory pathways IκBα/NF-κB and NLRP3-mediated pyroptosis","authors":"Anpeng Liu , Ling Xiao , Qianwen He , Zujin Xu, Yali Zhu, Zongze Zhang, Jia Zhan, Zhen Li","doi":"10.1016/j.micpath.2026.108309","DOIUrl":"10.1016/j.micpath.2026.108309","url":null,"abstract":"<div><div>The primary focus of sepsis therapy is to alleviate organ dysfunction. Sepsis-associated liver injury (SALI) occurs in about 40 % of sepsis patients, yet targeted therapeutic strategies remain unavailable. Electroacupuncture (EA) has emerged as a potential adjunctive therapy for sepsis, owing to its capacity to modulate the neuroendocrine-immune network. This study aims to investigate whether EA can alleviate SALI and its potential mechanisms. A murine model of sepsis was established via cecal ligation and puncture (CLP). The Zusanli (ST36) and Neiguan (PC6) acupoints, known for their anti-inflammatory properties, were selected for EA intervention. Following CLP, mice received EA stimulation at ST36 and PC6 for 20 min daily over two consecutive days. The results showed that EA significantly improved survival and attenuated SALI. Transcriptomic profiling via mRNA-seq uncovered immune cell gene expression changes in response to EA. Bioinformatics analysis indicated that EA downregulated genes involved in proinflammatory responses and leukocyte migration, which were enriched in Toll-like receptors and NOD-like receptors signaling pathways. Further research confirmed that EA significantly reduced serum levels of the proinflammatory cytokines IL-6, TNF-α, and IL-1β in septic mice. Mechanistically, EA suppressed activation of the proinflammatory signaling pathway IκBα/NF-κB and concurrently attenuated pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD axis in immune cells.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108309"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023721","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 : 2026-01-22DOI: 10.1016/j.micpath.2026.108314
Hévellin Talita Sousa Lins , Amanda Vieira de Barros , Tainara Fernandes Dantas , Patryck Érmerson Monteiro dos Santos , Fábio Henrique Galdino dos Santos , Daniela Maria do Amaral Ferraz Navarro , Márcia Vanusa da Silva , Patrícia Maria Guedes Paiva , Carina Lucena Mendes-Marques , Isadora Gomes de Souza , Celidarque da Silva Dias , Henrique Douglas Melo Coutinho , Maria Betânia Melo de Oliveira
The search for new drugs with antimicrobial activity is a global imperative. Therefore, the aim of the study was to assess the antimicrobial and modulatory activities of the essential oil from Myrciaria pilosa leaf (EOMP) and its main compound, 1,8-cineole (CNL), against resistant bacteria. So, initial the EOMP was obtained by hydrodistillation and analyzed by gas chromatography, identifying CNL as the main compound (34.51 %) present. The Minimum inhibitory concentration (MIC) tests were performed against resistant bacterial isolates of environmental and clinical origin. The results shows that the combination of EOMP and CNL with ampicillin (AMP) significantly reduced MIC values, with FICI values ranging from 0.005 to 1.0 against isolates of Staphylococcus schleiferi, Staphylococcus haemolyticus, Staphylococcus aureus, and Klebsiella oxytoca. As for the results of the growth curve and bacterial kill time assays, for K. oxytoca and S. haemolyticus showed a greater reduction in bacterial load compared to untreated strains. For the in vivo models with Tenebrio molitor, the treatments showed no toxic effects and were effective within the first 24 h in protecting the larvae against infections caused by resistant bacteria. These findings are the first report of the synergistic activity of EOMP with AMP, in addition to its in vivo effectiveness, and reinforce the synergistic potential of essential oils in combating bacterial resistance.
{"title":"In vitro and in vivo evaluation of antibacterial activity of 1,8-cineol and the essential oil of Myrciaria pilosa Sobral & Couto","authors":"Hévellin Talita Sousa Lins , Amanda Vieira de Barros , Tainara Fernandes Dantas , Patryck Érmerson Monteiro dos Santos , Fábio Henrique Galdino dos Santos , Daniela Maria do Amaral Ferraz Navarro , Márcia Vanusa da Silva , Patrícia Maria Guedes Paiva , Carina Lucena Mendes-Marques , Isadora Gomes de Souza , Celidarque da Silva Dias , Henrique Douglas Melo Coutinho , Maria Betânia Melo de Oliveira","doi":"10.1016/j.micpath.2026.108314","DOIUrl":"10.1016/j.micpath.2026.108314","url":null,"abstract":"<div><div>The search for new drugs with antimicrobial activity is a global imperative. Therefore, the aim of the study was to assess the antimicrobial and modulatory activities of the essential oil from <em>Myrciaria pilosa</em> leaf (EOMP) and its main compound, 1,8-cineole (CNL), against resistant bacteria. So, initial the EOMP was obtained by hydrodistillation and analyzed by gas chromatography, identifying CNL as the main compound (34.51 %) present. The Minimum inhibitory concentration (MIC) tests were performed against resistant bacterial isolates of environmental and clinical origin. The results shows that the combination of EOMP and CNL with ampicillin (AMP) significantly reduced MIC values, with FICI values ranging from 0.005 to 1.0 against isolates of <em>Staphylococcus schleiferi</em>, <em>Staphylococcus haemolyticus</em>, <em>Staphylococcus aureus</em>, and <em>Klebsiella oxytoca</em>. As for the results of the growth curve and bacterial kill time assays, for <em>K. oxytoca</em> and <em>S. haemolyticus</em> showed a greater reduction in bacterial load compared to untreated strains. For the <em>in vivo</em> models with <em>Tenebrio molitor</em>, the treatments showed no toxic effects and were effective within the first 24 h in protecting the larvae against infections caused by resistant bacteria. These findings are the first report of the synergistic activity of EOMP with AMP, in addition to its <em>in vivo</em> effectiveness, and reinforce the synergistic potential of essential oils in combating bacterial resistance.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108314"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023722","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 : 2026-01-22DOI: 10.1016/j.micpath.2026.108321
Arshad Ali , Ali Hassan , Imran Afzal , Hammad Hassan , Kirshan Chand , Hafiz Muhammad Usman , Xiaolong Liu , Min Lu
The rise of pesticide and antibiotic resistance has intensified the search for environmentally friendly alternatives to conventional chemical control agents. Green-synthesized nanoparticles, produced using plant extracts as natural reducing and capping agents, have attracted significant interest for their biocompatibility, stability, and strong biological activity. The current work aims to investigate the insecticidal efficiency of zinc oxide nanoparticles (ZnO-NPs) generated from Phoebe zhennan and Croton tiglium leaves against the various developmental stages of Plagiodera versicolora, a serious pest of Salicaceae plants and bacteria (Enterococcus faecalis and Enterobacter cloacae). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the formation of nanoparticles. The Fourier transform infrared (FTIR) spectrum confirms the presence of characteristic functional groups, indicating ZnO-NPs synthesis. X-ray diffraction (XRD) examination of ZnO-NPs revealed different peaks at certain 2θ angles, indicating different crystallographic planes. Different concentrations (6.25 mg/L, 12.5 mg/L, 25 mg/L, and 50 mg/L) of ZnO-NPs indicated that the increase in concentration and exposure period increased larval and adult mortality. The biosynthesized ZnO-NPs displayed potent, dose-dependent antibacterial effects against E. faecalis and E. cloacae. Both growth curve analysis and agar well-diffusion assays confirmed substantial inhibition of bacterial growth. In P. versicolora, exposure to ZnO-NPs led to progressive midgut epithelial disruption and necrosis, accompanied by a dose-dependent reduction in survival. LC50 values decreased steadily from 24 to 192 h, with LC90 values showing the same time-dependent decline. Overall, the study demonstrates that plant-derived ZnO-NPs provide a potent and sustainable approach for managing both insect pests and bacteria.
{"title":"Bioactivity of zinc oxide nanoparticles (ZnO-NPs) synthesized from Phoebe zhennan and Croton tiglium","authors":"Arshad Ali , Ali Hassan , Imran Afzal , Hammad Hassan , Kirshan Chand , Hafiz Muhammad Usman , Xiaolong Liu , Min Lu","doi":"10.1016/j.micpath.2026.108321","DOIUrl":"10.1016/j.micpath.2026.108321","url":null,"abstract":"<div><div>The rise of pesticide and antibiotic resistance has intensified the search for environmentally friendly alternatives to conventional chemical control agents. Green-synthesized nanoparticles, produced using plant extracts as natural reducing and capping agents, have attracted significant interest for their biocompatibility, stability, and strong biological activity. The current work aims to investigate the insecticidal efficiency of zinc oxide nanoparticles (ZnO-NPs) generated from <em>Phoebe zhennan</em> and <em>Croton tiglium</em> leaves against the various developmental stages of <em>Plagiodera versicolora</em>, a serious pest of <em>Salicaceae</em> plants and bacteria (<em>Enterococcus faecalis</em> and <em>Enterobacter cloacae</em>). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the formation of nanoparticles. The Fourier transform infrared (FTIR) spectrum confirms the presence of characteristic functional groups, indicating ZnO-NPs synthesis. X-ray diffraction (XRD) examination of ZnO-NPs revealed different peaks at certain 2θ angles, indicating different crystallographic planes. Different concentrations (6.25 mg/L, 12.5 mg/L, 25 mg/L, and 50 mg/L) of ZnO-NPs indicated that the increase in concentration and exposure period increased larval and adult mortality. The biosynthesized ZnO-NPs displayed potent, dose-dependent antibacterial effects against <em>E</em>. <em>faecalis</em> and <em>E</em>. <em>cloacae</em>. Both growth curve analysis and agar well-diffusion assays confirmed substantial inhibition of bacterial growth. In <em>P. versicolora</em>, exposure to ZnO-NPs led to progressive midgut epithelial disruption and necrosis, accompanied by a dose-dependent reduction in survival. LC<sub>50</sub> values decreased steadily from 24 to 192 h, with LC<sub>90</sub> values showing the same time-dependent decline. Overall, the study demonstrates that plant-derived ZnO-NPs provide a potent and sustainable approach for managing both insect pests and bacteria.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108321"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044312","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}
Streptococcus suis causes severe disease in pigs and is implicated increasingly in human infections, posing a substantial zoonotic threat to global public health, with many human and pig infections being caused by S. suis serotype 2, especially strains belonging to clonal complex (CC) 1. However, infections due to non-serotype 2 and non CC1 have been increasing worldwide, especially CC94. This study investigated the genome characteristics and virulence capacity of S. suis serotype 4 ST1689. Whole genome sequencing, cytotoxicity, adhesion, invasion, apoptosis, hemolytic assay, and a mouse experiment were conducted. The genomic analysis revealed that serotype 4 ST1689 strain 3453 was classified into minimum core-genome group 3 and that the serotype 4 isolate was closely related with the porcine strains from Thailand. Furthermore, this strain carried genes conferring resistance to macrolide (ermB), tetracycline tet(O), aminoglycoside (spw), and lincosamide (lsa(E), lnu(B)). This strain was multidrug resistant with resistance to penicillin, cefepime, cefotaxime, azithromycin, erythromycin, and tetracycline. β-lactam resistance in this strain was associated with the mutations in the PBP1A, PBP2B, and PBP2X proteins. In addition, the adhesion and invasion capacity were significantly lower than S. suis serotype 2 (P1/7). There was a strong cytotoxic, apoptotic effect on the epithelial cell line, similar to strain P1/7. In addition, this strain produced 80 % and 100 % mortality rates in a mouse model within 12 h and 24 h post-infection, respectively. Mice infected with S. suis serotype 4-ST1689 strain exhibited a higher bacteria burden, particular in the blood (p < 0.05), brain (p < 0.001) and kidney (p < 0.01) compared with serotype 2 (P1/7)-infected mice. S. suis serotype 4-ST1689 strain infection induced an acute and extremely high inflammatory cytokine response, including significantly (p < 0.001) increased IL-6, IL-1β, and TNF-α levels. These results suggested that the highly virulent S. suis serotype 4-ST1689 strain induced high levels of pro-inflammatory mediators and invasion of multiple organs, subsequence leading to high mortality. These results should provide important insights into the development of control strategies for transmission of S. suis serotype 4 ST1689 in public and pig farms.
{"title":"WGS analysis and virulence of Streptococcus suis serotype 4 ST1689 isolated from an asymptomatic pig, Thailand","authors":"Nattamol Phetburom , Thotsaporn Bunthiang , Siriwan Sunontarat , Ratchadawan Aukkanimart , Pranee Sriraj , Ekkachai Kanchanatip , Rujirat Hatrongjit , Peechanika Chopjitt , Anusak Kerdsin , Parichart Boueroy","doi":"10.1016/j.micpath.2026.108324","DOIUrl":"10.1016/j.micpath.2026.108324","url":null,"abstract":"<div><div><em>Streptococcus suis</em> causes severe disease in pigs and is implicated increasingly in human infections, posing a substantial zoonotic threat to global public health, with many human and pig infections being caused by <em>S. suis</em> serotype 2, especially strains belonging to clonal complex (CC) 1. However, infections due to non-serotype 2 and non CC1 have been increasing worldwide, especially CC94. This study investigated the genome characteristics and virulence capacity of <em>S</em>. <em>suis</em> serotype 4 ST1689. Whole genome sequencing, cytotoxicity, adhesion, invasion, apoptosis, hemolytic assay, and a mouse experiment were conducted. The genomic analysis revealed that serotype 4 ST1689 strain 3453 was classified into minimum core-genome group 3 and that the serotype 4 isolate was closely related with the porcine strains from Thailand. Furthermore, this strain carried genes conferring resistance to macrolide (<em>ermB</em>), tetracycline <em>tet(O),</em> aminoglycoside (<em>spw</em>), and lincosamide (<em>lsa(E), lnu(B)</em>). This strain was multidrug resistant with resistance to penicillin, cefepime, cefotaxime, azithromycin, erythromycin, and tetracycline. β-lactam resistance in this strain was associated with the mutations in the PBP1A, PBP2B, and PBP2X proteins. In addition, the adhesion and invasion capacity were significantly lower than <em>S. suis</em> serotype 2 (P1/7). There was a strong cytotoxic, apoptotic effect on the epithelial cell line, similar to strain P1/7. In addition, this strain produced 80 % and 100 % mortality rates in a mouse model within 12 h and 24 h post-infection, respectively. Mice infected with <em>S. suis</em> serotype 4-ST1689 strain exhibited a higher bacteria burden, particular in the blood (p < 0.05), brain (p < 0.001) and kidney (p < 0.01) compared with serotype 2 (P1/7)-infected mice. <em>S. suis</em> serotype 4-ST1689 strain infection induced an acute and extremely high inflammatory cytokine response, including significantly (p < 0.001) increased IL-6, IL-1β, and TNF-α levels. These results suggested that the highly virulent <em>S. suis</em> serotype 4-ST1689 strain induced high levels of pro-inflammatory mediators and invasion of multiple organs, subsequence leading to high mortality. These results should provide important insights into the development of control strategies for transmission of <em>S. suis</em> serotype 4 ST1689 in public and pig farms.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108324"},"PeriodicalIF":3.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044307","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 : 2026-01-21DOI: 10.1016/j.micpath.2026.108313
Zhao Wang, Xinwen Yu, Dongni Ren
Brucella-induced microglial inflammation plays a pivotal role in the neuropathology of neurobrucellosis. The virulence factor BvrR, critical for Brucella replication and survival within the host cell's endoplasmic reticulum (ER), has an undefined role in this inflammatory process. To elucidate this, HMC3 cells were transfected with pcDNA3.1-BvrR-His to investigate the impact of Brucella abortus BvrR on the ER and the activation of ATF2 and NF-κB p65 proteins. To support the hypothesis that BvrR mediates activation of the ATF2/IL-6 and NF-κB p65/TNF-α pathways via p-IRE1, the effects of the IRE1 activator IXA4 and inhibitor GSK2850163 on these pathways were evaluated. HMC3 cells expressing BvrR were treated with IXA4 and GSK2850163. Protein and mRNA expression levels were determined by Western blot and RT-qPCR, while IL-6 and TNF-α concentrations in the supernatant were quantified by ELISA. Results indicated that BvrR activated IRE1, which subsequently triggered the ATF2/IL-6 and NF-κB p65/TNF-α pathways. For in vivo analysis, HBAAV2/9-IBA1-BvrR-6*HIS-ZsGreen was stereotactically injected into the right hippocampus of mice. Hippocampal neuronal damage and cognitive function were evaluated using Nissl staining and the Morris water maze test. Additionally, IRE1, ATF2/IL-6, and NF-κB p65/TNF-α signaling were analyzed in hippocampal microglia by immunofluorescence and Western blot. These findings demonstrated that Brucella abortus BvrR activates microglial inflammatory pathways via p-IRE1, leading to neuronal damage.
{"title":"BvrR of Brucella initiates microglial inflammation through the activation of the IRE1 pathway.","authors":"Zhao Wang, Xinwen Yu, Dongni Ren","doi":"10.1016/j.micpath.2026.108313","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108313","url":null,"abstract":"<p><p>Brucella-induced microglial inflammation plays a pivotal role in the neuropathology of neurobrucellosis. The virulence factor BvrR, critical for Brucella replication and survival within the host cell's endoplasmic reticulum (ER), has an undefined role in this inflammatory process. To elucidate this, HMC3 cells were transfected with pcDNA3.1-BvrR-His to investigate the impact of Brucella abortus BvrR on the ER and the activation of ATF2 and NF-κB p65 proteins. To support the hypothesis that BvrR mediates activation of the ATF2/IL-6 and NF-κB p65/TNF-α pathways via p-IRE1, the effects of the IRE1 activator IXA4 and inhibitor GSK2850163 on these pathways were evaluated. HMC3 cells expressing BvrR were treated with IXA4 and GSK2850163. Protein and mRNA expression levels were determined by Western blot and RT-qPCR, while IL-6 and TNF-α concentrations in the supernatant were quantified by ELISA. Results indicated that BvrR activated IRE1, which subsequently triggered the ATF2/IL-6 and NF-κB p65/TNF-α pathways. For in vivo analysis, HBAAV2/9-IBA1-BvrR-6*HIS-ZsGreen was stereotactically injected into the right hippocampus of mice. Hippocampal neuronal damage and cognitive function were evaluated using Nissl staining and the Morris water maze test. Additionally, IRE1, ATF2/IL-6, and NF-κB p65/TNF-α signaling were analyzed in hippocampal microglia by immunofluorescence and Western blot. These findings demonstrated that Brucella abortus BvrR activates microglial inflammatory pathways via p-IRE1, leading to neuronal damage.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108313"},"PeriodicalIF":3.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040950","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 : 2026-01-21DOI: 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":"2026-01-21","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}
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