Pub Date : 2025-11-28DOI: 10.1016/j.micpath.2025.108215
Xiao-Le Han , Jiang Chen , Tao Zhou , Jianming Xu , Le Dai , Yi Liu
This study evaluates the natural product Equisetin as a potent agent against multidrug-resistant Enterococcus faecalis (MDR E. faecalis). Equisetin exhibited strong antibacterial activity (MIC = 5.84 μg/mL) by disrupting membrane integrity, inducing protein/DNA leakage, depolarizing membrane potential, elevating ROS, and depleting ATP. It also inhibited biofilm formation and showed minimal hemolytic activity without inducing resistance. Transcriptomics revealed upregulation of DNA repair/stress genes and downregulation of metabolic/protein synthesis genes, indicating a multi-target mechanism. These findings position Equisetin as a promising candidate for treating MDR infections.
本研究评价了天然产物马粪素作为抗多药耐药粪肠球菌（MDR E. faecalis）的有效药物。Equisetin通过破坏膜完整性、诱导蛋白/DNA渗漏、去极化膜电位、升高ROS和消耗ATP等方式表现出较强的抗菌活性（MIC = 5.84 μg/mL）。它还能抑制生物膜的形成，并表现出最小的溶血活性，而不会引起耐药性。转录组学显示DNA修复/应激基因上调，代谢/蛋白质合成基因下调，提示多靶点机制。这些发现使Equisetin成为治疗耐多药感染的有希望的候选药物。
{"title":"Equisetin targets membrane integrity and transcriptional networks to combat multidrug-resistant Enterococcus faecalis","authors":"Xiao-Le Han , Jiang Chen , Tao Zhou , Jianming Xu , Le Dai , Yi Liu","doi":"10.1016/j.micpath.2025.108215","DOIUrl":"10.1016/j.micpath.2025.108215","url":null,"abstract":"<div><div>This study evaluates the natural product Equisetin as a potent agent against multidrug-resistant <em>Enterococcus faecalis</em> (MDR <em>E. faecalis</em>). Equisetin exhibited strong antibacterial activity (MIC = 5.84 μg/mL) by disrupting membrane integrity, inducing protein/DNA leakage, depolarizing membrane potential, elevating ROS, and depleting ATP. It also inhibited biofilm formation and showed minimal hemolytic activity without inducing resistance. Transcriptomics revealed upregulation of DNA repair/stress genes and downregulation of metabolic/protein synthesis genes, indicating a multi-target mechanism. These findings position Equisetin as a promising candidate for treating MDR infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108215"},"PeriodicalIF":3.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635886","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 : 2025-11-27DOI: 10.1016/j.micpath.2025.108213
Carmela Colica, Immacolata Vecchio
Chronic non-communicable diseases (CNCDs), including obesity, type 2 diabetes, allergies, and autoimmune conditions, represent a significant global health burden, exacerbated by the interplay between genetic and environmental factors, such as diet, and gut microbiota. The gut microbiota is a complex and dynamic microbial community that influences host immune and metabolic systems from birth through adulthood. Dysbiosis - an imbalance in gut microbial composition - has been implicated in the development of low-grade inflammation, insulin resistance, and metabolic and immune disorders. This paper reviews the critical role of gut microbiota in CNCDs, emphasizing its interactions with the immune system, including regulatory T cell induction and the Th1/Th2 balance. Furthermore, it explores the influence of birth mode, diet, and xenobiotics on microbiota composition and function. Finally, the study highlights the potential of microbiota-targeted interventions - such as prebiotics, probiotics, synbiotics, and fecal microbiota transplantation - to modulate gut ecology and mitigate disease risk. From literature revision emerges the need for integrative approaches in disease prevention and management, considering microbiota as a key player in health and disease.
{"title":"Gut microbiota: origin or panacea for all ills? Part 1: Immune and Metabolic Diseases, Nutrition, and Microbiota-Based Interventions.","authors":"Carmela Colica, Immacolata Vecchio","doi":"10.1016/j.micpath.2025.108213","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.108213","url":null,"abstract":"<p><p>Chronic non-communicable diseases (CNCDs), including obesity, type 2 diabetes, allergies, and autoimmune conditions, represent a significant global health burden, exacerbated by the interplay between genetic and environmental factors, such as diet, and gut microbiota. The gut microbiota is a complex and dynamic microbial community that influences host immune and metabolic systems from birth through adulthood. Dysbiosis - an imbalance in gut microbial composition - has been implicated in the development of low-grade inflammation, insulin resistance, and metabolic and immune disorders. This paper reviews the critical role of gut microbiota in CNCDs, emphasizing its interactions with the immune system, including regulatory T cell induction and the Th1/Th2 balance. Furthermore, it explores the influence of birth mode, diet, and xenobiotics on microbiota composition and function. Finally, the study highlights the potential of microbiota-targeted interventions - such as prebiotics, probiotics, synbiotics, and fecal microbiota transplantation - to modulate gut ecology and mitigate disease risk. From literature revision emerges the need for integrative approaches in disease prevention and management, considering microbiota as a key player in health and disease.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108213"},"PeriodicalIF":3.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635822","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 : 2025-11-27DOI: 10.1016/j.micpath.2025.108208
Te Chen , Jiayu Liu , Renlin Yu , Yan Wu , Qin Luo , Haofeng Xu , Wenchun Xu , Xuemei Zhang , Yibing Yin
Secondary bacterial pneumonia is a common cause of influenza infection associated deaths. This study investigated the potential therapeutic role of inhibiting toll-like receptor 7 (TLR7) in influenza-associated Staphylococcus aureus (S.aureus) coinfection. Both TLR7 deficiency and TLR7 antagonist IRS661 treatment significantly improved survival in mice coinfected with influenza virus (PR8) and S.aureus while significantly reducing pulmonary damage as evidenced by decreased total protein (TP) and lactate dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF) and serum alanine aminotransferase (ALT) and urea nitrogen (UREA) levels. Notably, both interventions significantly maintained the accumulated inflammatory infiltration observed within 6 h post-coinfection, and up to 48 h. Mechanistically, IRS661 enhanced macrophage phagocytosis, bactericidal activity, and reactive oxygen species (ROS) production ex vivo and in vivo. This effect was correlated with reduced c-Jun N-terminal kinase (JNK) phosphorylation. Furthermore, during early infection, this modulation was accompanied by significantly reduced levels of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, but a concomitant increase in IFN-γ. Transcriptomic analysis revealed IRS661 modulated pathways involved in cell adhesion, metabolism, and oxidative stress response. These findings suggested that TLR7 antagonism, specifically through IRS661, represented a promising therapeutic strategy for influenza-associated secondary bacterial infections, paving further investigations into its clinical translation potential.
继发性细菌性肺炎是流感感染相关死亡的常见原因。本研究探讨了抑制toll样受体7 （TLR7）在流感相关金黄色葡萄球菌（金黄色葡萄球菌）合并感染中的潜在治疗作用。TLR7缺乏症和TLR7拮抗剂IRS661治疗均可显著提高流感病毒（PR8）和金黄色葡萄球菌联合感染小鼠的存活率，同时显著减轻肺损伤，这可以通过降低支气管肺泡灌洗液（BALF）中总蛋白（TP）和乳酸脱氢酶（LDH）水平以及血清丙氨酸转氨酶（ALT）和尿素氮（urea）水平来证明。值得注意的是，两种干预措施都显著维持了合并感染后6小时内观察到的累积炎症浸润，最长可达48小时。在机制上，IRS661增强了巨噬细胞的吞噬作用、杀菌活性和体内外活性氧（ROS）的产生。这种效应与c-Jun n -末端激酶（JNK）磷酸化降低有关。此外，在早期感染期间，这种调节伴随着促炎细胞因子水平的显著降低，包括IL-6、IL-1β和TNF-α，但同时伴随着IFN-γ的增加。转录组学分析显示，IRS661调控的途径参与细胞粘附、代谢和氧化应激反应。这些发现表明，TLR7拮抗剂，特别是通过IRS661，代表了一种有希望的治疗流感相关继发性细菌感染的策略，为进一步研究其临床转化潜力奠定了基础。
{"title":"Targeting TLR7 reprograms macrophage function to attenuate influenza-associated Staphylococcus aureus coinfection","authors":"Te Chen , Jiayu Liu , Renlin Yu , Yan Wu , Qin Luo , Haofeng Xu , Wenchun Xu , Xuemei Zhang , Yibing Yin","doi":"10.1016/j.micpath.2025.108208","DOIUrl":"10.1016/j.micpath.2025.108208","url":null,"abstract":"<div><div>Secondary bacterial pneumonia is a common cause of influenza infection associated deaths. This study investigated the potential therapeutic role of inhibiting toll-like receptor 7 (TLR7) in influenza-associated <em>Staphylococcus aureus</em> (<em>S.aureus</em>) coinfection. Both TLR7 deficiency and TLR7 antagonist IRS661 treatment significantly improved survival in mice coinfected with influenza virus (PR8) and <em>S.aureus</em> while significantly reducing pulmonary damage as evidenced by decreased total protein (TP) and lactate dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF) and serum alanine aminotransferase (ALT) and urea nitrogen (UREA) levels. Notably, both interventions significantly maintained the accumulated inflammatory infiltration observed within 6 h post-coinfection, and up to 48 h. Mechanistically, IRS661 enhanced macrophage phagocytosis, bactericidal activity, and reactive oxygen species (ROS) production <em>ex vivo</em> and <em>in vivo</em>. This effect was correlated with reduced c-Jun N-terminal kinase (JNK) phosphorylation. Furthermore, during early infection, this modulation was accompanied by significantly reduced levels of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, but a concomitant increase in IFN-γ. Transcriptomic analysis revealed IRS661 modulated pathways involved in cell adhesion, metabolism, and oxidative stress response. These findings suggested that TLR7 antagonism, specifically through IRS661, represented a promising therapeutic strategy for influenza-associated secondary bacterial infections, paving further investigations into its clinical translation potential.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108208"},"PeriodicalIF":3.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635875","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 : 2025-11-27DOI: 10.1016/j.micpath.2025.108214
Xunyao Zhang , Jiahao Yuan , Aijun Li , Gang Yang , Xiaowei Peng , Huijing Chen , Jianquan Kan
Tinea pedis, a common superficial cutaneous fungal infection, substantially affects patients' quality of life and may also lead to complications such as secondary infections. Zanthoxylum schinifolium (ZS) seeds, a traditional dual-purpose resource with medicinal and culinary uses, possess various pharmacological properties, including lipid-lowering, antioxidant, and antibacterial effects. However, the specific active components and mechanisms underlying their inhibitory activities against tinea pedis remain unclear. This is the first study to isolate and identify four active compounds (fargesin, kobusin, prudomestin, and sesamin) from ZS seeds with inhibitory activities against tinea pedis. In vitro antifungal experiments demonstrated that these compounds exhibited significant inhibitory effects on Trichophyton rubrum and Trichophyton interdigitale, with kobusin showing the most potent antifungal activity, as indicated by a minimum inhibitory concentration of 0.039 mg/mL against both pathogens. Further studies revealed that kobusin inhibits spore germination and hyphal growth, disrupts cell membrane integrity and potential, and causes leakage of nucleic acids and proteins. Simultaneously, it causes severe damage to hyphal morphology and structure while inducing lipid peroxidation and reactive oxygen species accumulation, coupled with the suppression of antioxidant enzyme activity, ultimately triggering oxidative stress-mediated hyphal apoptosis. Additionally, it disrupts the cellular respiratory chain and energy metabolism, resulting in the comprehensive inhibition of the normal growth of T. rubrum. Notably, kobusin exhibits low cytotoxicity toward HEK 293 and RAW 264.7 cells. This study provides an important theoretical foundation for the development of ZS seeds as a natural antifungal agent.
{"title":"Antifungal Compounds from Zanthoxylum schinifolium Seeds against Tinea Pedis fungus: Isolation, Identification and Mechanism of Action","authors":"Xunyao Zhang , Jiahao Yuan , Aijun Li , Gang Yang , Xiaowei Peng , Huijing Chen , Jianquan Kan","doi":"10.1016/j.micpath.2025.108214","DOIUrl":"10.1016/j.micpath.2025.108214","url":null,"abstract":"<div><div>Tinea pedis, a common superficial cutaneous fungal infection, substantially affects patients' quality of life and may also lead to complications such as secondary infections. <em>Zanthoxylum schinifolium</em> (<em>ZS</em>) seeds, a traditional dual-purpose resource with medicinal and culinary uses, possess various pharmacological properties, including lipid-lowering, antioxidant, and antibacterial effects. However, the specific active components and mechanisms underlying their inhibitory activities against tinea pedis remain unclear. This is the first study to isolate and identify four active compounds (fargesin, kobusin, prudomestin, and sesamin) from <em>ZS</em> seeds with inhibitory activities against tinea pedis. <em>In vitro</em> antifungal experiments demonstrated that these compounds exhibited significant inhibitory effects on <em>Trichophyton rubrum</em> and <em>Trichophyton interdigitale</em>, with kobusin showing the most potent antifungal activity, as indicated by a minimum inhibitory concentration of 0.039 mg/mL against both pathogens. Further studies revealed that kobusin inhibits spore germination and hyphal growth, disrupts cell membrane integrity and potential, and causes leakage of nucleic acids and proteins. Simultaneously, it causes severe damage to hyphal morphology and structure while inducing lipid peroxidation and reactive oxygen species accumulation, coupled with the suppression of antioxidant enzyme activity, ultimately triggering oxidative stress-mediated hyphal apoptosis. Additionally, it disrupts the cellular respiratory chain and energy metabolism, resulting in the comprehensive inhibition of the normal growth of <em>T. rubrum</em>. Notably, kobusin exhibits low cytotoxicity toward HEK 293 and RAW 264.7 cells. This study provides an important theoretical foundation for the development of <em>ZS</em> seeds as a natural antifungal agent.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108214"},"PeriodicalIF":3.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615384","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 : 2025-11-27DOI: 10.1016/j.micpath.2025.108206
Jin-Li Ding , Jie Zhu , Mei Liu , Min Lu , Ming-Guang Feng , Sheng-Hua Ying
This study establishes the MBF transcription complex (BbSwi6/BbMbp1) as a central regulator of lipid metabolism and virulence in Beauveria bassiana by directly controlling the short-chain dehydrogenase/reductase (SDR) gene BbOSD. Deletion of BbSWI6, BbMBP1 and BbOSD caused severe lipid dysregulation, including a significant reduction in mycelial lipids and, critically, failure to deplete host lipids during Galleria mellonella infection. This impaired host lipid assimilation underlies the mutants' attenuated virulence. BbOSD expression was drastically downregulated in MBF mutants and required for wild-type levels of dramatic induction (∼10-fold) when lipids served as the sole carbon source. Yeast one-hybrid confirmed BbMbp1 binding to the BbOSD promoter, establishing MBF-mediated metabolic reprogramming towards lipid catabolism during nutrient stress. BbOsd, structurally confirmed as an SDR, dynamically localized to lipid droplets during exogenous lipid utilization. BbOSD deletion severely impaired asexual reproduction, with conidiation and blastospore production reductions exacerbated under lipid-rich conditions. The ΔBbosd mutant also exhibited heightened sensitivity to oxidative stress and catastrophically diminished blastospore yield under oxidative challenge. Consequently, virulence was significantly attenuated via different infection routes. Collectively, the MBF-BbOSD axis integrates lipid homeostasis, development, and oxidative defense. Disruption simultaneously compromises these functions, directly diminishing virulence. This work fundamentally expands the conserved MBF complex's role beyond cell cycle regulation, positioning efficient lipid metabolism orchestrated by MBF-BbOSD as a cornerstone of entomopathogenicity.
{"title":"The MBF complex orchestrates BbOSD-mediated lipid metabolism, development, oxidative stress, and pathogenic virulence in Beauveria bassiana","authors":"Jin-Li Ding , Jie Zhu , Mei Liu , Min Lu , Ming-Guang Feng , Sheng-Hua Ying","doi":"10.1016/j.micpath.2025.108206","DOIUrl":"10.1016/j.micpath.2025.108206","url":null,"abstract":"<div><div>This study establishes the MBF transcription complex (BbSwi6/BbMbp1) as a central regulator of lipid metabolism and virulence in <em>Beauveria bassiana</em> by directly controlling the short-chain dehydrogenase/reductase (SDR) gene <em>BbOSD</em>. Deletion of <em>BbSWI6</em>, <em>BbMBP1</em> and <em>BbOSD</em> caused severe lipid dysregulation, including a significant reduction in mycelial lipids and, critically, failure to deplete host lipids during <em>Galleria mellonella</em> infection. This impaired host lipid assimilation underlies the mutants' attenuated virulence. <em>BbOSD</em> expression was drastically downregulated in MBF mutants and required for wild-type levels of dramatic induction (∼10-fold) when lipids served as the sole carbon source. Yeast one-hybrid confirmed BbMbp1 binding to the <em>BbOSD</em> promoter, establishing MBF-mediated metabolic reprogramming towards lipid catabolism during nutrient stress. BbOsd, structurally confirmed as an SDR, dynamically localized to lipid droplets during exogenous lipid utilization. <em>BbOSD</em> deletion severely impaired asexual reproduction, with conidiation and blastospore production reductions exacerbated under lipid-rich conditions. The Δ<em>Bbosd</em> mutant also exhibited heightened sensitivity to oxidative stress and catastrophically diminished blastospore yield under oxidative challenge. Consequently, virulence was significantly attenuated via different infection routes. Collectively, the MBF-<em>BbOSD</em> axis integrates lipid homeostasis, development, and oxidative defense. Disruption simultaneously compromises these functions, directly diminishing virulence. This work fundamentally expands the conserved MBF complex's role beyond cell cycle regulation, positioning efficient lipid metabolism orchestrated by MBF-<em>BbOSD</em> as a cornerstone of entomopathogenicity.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108206"},"PeriodicalIF":3.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635829","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}
Tuberculosis (TB) emphasises the critical need for quick and precise diagnosis techniques as well as treatment response monitoring, as it has become a major global source of disease and mortality. In this present study, saliva samples from 46 patients with newly diagnosed active pulmonary tuberculosis (PTB), 46 patients with other respiratory disorders (ORD) and 46 Healthy Individuals (HI) were collected and evaluated for the concentrations of 37 host biomarkers using Luminex multiplex immunoassay. Significant variations between groups have been identified in the diagnostic accuracy of biomarkers as assessed by multiple logistic regression and area under curve (AUC). Fractalkine exhibited the greatest diagnostic accuracy and discriminatory capability, with high sensitivity, and specificity, highlighting its effectiveness as the best biomarker for differentiating PTB patients from ORD cases and HI. The five-marker combination (Fractalkine + VEGF + IL-23+IL-17A + GM-CSF) achieved the best diagnostic performance, with an AUC of 0.98, accuracy of 90.2 % suggesting a strong ability to identify PTB cases from ORD. In addition, the five-marker panel (Fractalkine + IL-1α+ GRO + IP-10+MCP-1) achieved excellent performance with an AUC of 0.99 and an accuracy of 92.4 %, for distinguishing PTB from HI. The salivary concentrations of Fractalkine, IL-17A, IL-23, and VEGF decreased significantly at 2 and 6 months, indicating their potential as biomarkers for monitoring TB treatment responses. These findings provide valuable insights into non-invasive TB diagnostics and treatment monitoring, warranting further validation in a larger cohort to facilitate clinical translation.
{"title":"Exploring immunological host biosignatures in saliva: A novel framework for early diagnosis and treatment response for pulmonary tuberculosis infection","authors":"Pavithra Selvan , Nalini Jayanthi Nagesh , Leela Kakithakara Vajravelu","doi":"10.1016/j.micpath.2025.108212","DOIUrl":"10.1016/j.micpath.2025.108212","url":null,"abstract":"<div><div>Tuberculosis (TB) emphasises the critical need for quick and precise diagnosis techniques as well as treatment response monitoring, as it has become a major global source of disease and mortality. In this present study, saliva samples from 46 patients with newly diagnosed active pulmonary tuberculosis (PTB), 46 patients with other respiratory disorders (ORD) and 46 Healthy Individuals (HI) were collected and evaluated for the concentrations of 37 host biomarkers using Luminex multiplex immunoassay. Significant variations between groups have been identified in the diagnostic accuracy of biomarkers as assessed by multiple logistic regression and area under curve (AUC). Fractalkine exhibited the greatest diagnostic accuracy and discriminatory capability, with high sensitivity, and specificity, highlighting its effectiveness as the best biomarker for differentiating PTB patients from ORD cases and HI. The five-marker combination (Fractalkine + VEGF + IL-23+IL-17A + GM-CSF) achieved the best diagnostic performance, with an AUC of 0.98, accuracy of 90.2 % suggesting a strong ability to identify PTB cases from ORD. In addition, the five-marker panel (Fractalkine + IL-1α+ GRO + IP-10+MCP-1) achieved excellent performance with an AUC of 0.99 and an accuracy of 92.4 %, for distinguishing PTB from HI. The salivary concentrations of Fractalkine, IL-17A, IL-23, and VEGF decreased significantly at 2 and 6 months, indicating their potential as biomarkers for monitoring TB treatment responses. These findings provide valuable insights into non-invasive TB diagnostics and treatment monitoring, warranting further validation in a larger cohort to facilitate clinical translation.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108212"},"PeriodicalIF":3.5,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615359","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 : 2025-11-25DOI: 10.1016/j.micpath.2025.108210
Sandip Patil , Yali Wu , Lu Huang , Zihao Liu , Jiali Gu , Chunyan Liu , Heping Wang , Chunqing Zhu , Yunsheng Chen , Yuejie Zheng , Shaowei Dong , Yanmin Bao
Streptococcus pneumoniae remains a major cause of lower respiratory tract infections (LRTIs) in children, and the introduction of pneumococcal conjugate vaccines has altered serotype circulation in many regions. In China, PCV13 has been available since 2016 as a voluntary, self-paying vaccine, resulting in uneven coverage across populations. This retrospective study analyzed 425 children under 14 years of age with culture-confirmed S. pneumoniae LRTIs treated at Shenzhen Children's Hospital between 2021 and 2022, comparing serotype distribution and antibiotic resistance profiles according to PCV13 vaccination status. A total of 40 serotypes were identified. Serotype 19F remained the most prevalent (n = 150), particularly among unvaccinated children, and was strongly associated with pneumonia. Serotypes 23A and 23F were also frequently detected. Vaccinated children exhibited lower proportions of PCV13-included serotypes, whereas unvaccinated children demonstrated higher rates of multidrug-resistant isolates. Additionally, emerging non-vaccine serotypes such as 15A and 6E were observed, suggesting early signs of serotype replacement under partial vaccine uptake. These findings highlight ongoing circulation of invasive and drug-resistant pneumococcal serotypes in children, especially those without PCV13 immunization. Strengthening vaccine coverage and sustaining serotype surveillance are critical to guide future immunization policy and antimicrobial stewardship strategies in China.
{"title":"Pneumococcal serotypes and resistance profiles among children with and without PCV13 vaccination in Shenzhen, China","authors":"Sandip Patil , Yali Wu , Lu Huang , Zihao Liu , Jiali Gu , Chunyan Liu , Heping Wang , Chunqing Zhu , Yunsheng Chen , Yuejie Zheng , Shaowei Dong , Yanmin Bao","doi":"10.1016/j.micpath.2025.108210","DOIUrl":"10.1016/j.micpath.2025.108210","url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em> remains a major cause of lower respiratory tract infections (LRTIs) in children, and the introduction of pneumococcal conjugate vaccines has altered serotype circulation in many regions. In China, PCV13 has been available since 2016 as a voluntary, self-paying vaccine, resulting in uneven coverage across populations. This retrospective study analyzed 425 children under 14 years of age with culture-confirmed <em>S. pneumoniae</em> LRTIs treated at Shenzhen Children's Hospital between 2021 and 2022, comparing serotype distribution and antibiotic resistance profiles according to PCV13 vaccination status. A total of 40 serotypes were identified. Serotype 19F remained the most prevalent (n = 150), particularly among unvaccinated children, and was strongly associated with pneumonia. Serotypes 23A and 23F were also frequently detected. Vaccinated children exhibited lower proportions of PCV13-included serotypes, whereas unvaccinated children demonstrated higher rates of multidrug-resistant isolates. Additionally, emerging non-vaccine serotypes such as 15A and 6E were observed, suggesting early signs of serotype replacement under partial vaccine uptake. These findings highlight ongoing circulation of invasive and drug-resistant pneumococcal serotypes in children, especially those without PCV13 immunization. Strengthening vaccine coverage and sustaining serotype surveillance are critical to guide future immunization policy and antimicrobial stewardship strategies in China.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108210"},"PeriodicalIF":3.5,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615385","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}
The continuous increase in multidrug-resistant (MDR) bacteria has limited the usage of antibiotics, creating an urgent need to discover the potential efficacy of alternative products. The present study investigates Chlorophyllum molybdites, a toxic mushroom that contains a diverse range of bioactive compounds. The study focuses on the morphological to molecular identification of mushrooms and evaluates the bioactive compounds and their antioxidant and antibacterial properties. Silver nanoparticles (AgNPs) were synthesized using the green synthesis method, characterized by UV–Vis spectrophotometry, DLS, FTIR, XRD, TEM, and tested for their antibacterial properties against Salmonella typhi and Bacillus cereus. AgNPs demonstrated significantly improved antibacterial activity as compared to C. molybdites crude and broth-derived extract. The antibacterial activity of cloth-coated AgNPs was also confirmed, showing significant inhibition on both pathogens, and suggesting potential application in wound dressings and infection control. In addition, synthesized AgNPs exhibited high selectivity for L-cysteine hydrochloride among amino acids, indicating their utility as reliable colourimetric nanoprobes for cysteine detection. Furthermore, bioactive compounds in the crude and broth extracts were analysed using Orbitrap High-Resolution LC-MS, revealing major novel compounds including betaine, methylimidazoleacetic acid, L-norleucine, choline, DL-carnitine, hypoxanthine, hexadecanamide, and linoleoyl ethanolamide. This study opens a new avenue for the large-scale production of C. molybdites bioactive compounds, which may be valuable in future efforts to combat infections caused by MDR bacteria.
{"title":"Green synthesis of silver nanoparticles from Chlorophyllum molybdites: A multifunctional platform for antibacterial cloth development and colourimetric detection of L-Cysteine","authors":"Khemraj Sahu , Pritika Pradhan , Rajiv Nayan , Shubhra Sinha , Vaibhav Dixit , Indrapal Karbhal , Shailesh Kumar Jadhav , Nagendra Kumar Chandrawanshi","doi":"10.1016/j.micpath.2025.108205","DOIUrl":"10.1016/j.micpath.2025.108205","url":null,"abstract":"<div><div>The continuous increase in multidrug-resistant (MDR) bacteria has limited the usage of antibiotics, creating an urgent need to discover the potential efficacy of alternative products. The present study investigates <em>Chlorophyllum molybdites</em>, a toxic mushroom that contains a diverse range of bioactive compounds. The study focuses on the morphological to molecular identification of mushrooms and evaluates the bioactive compounds and their antioxidant and antibacterial properties. Silver nanoparticles (AgNPs) were synthesized using the green synthesis method, characterized by UV–Vis spectrophotometry, DLS, FTIR, XRD, TEM, and tested for their antibacterial properties against <em>Salmonella typhi</em> and <em>Bacillus cereus</em>. AgNPs demonstrated significantly improved antibacterial activity as compared to <em>C. molybdites</em> crude and broth-derived extract. The antibacterial activity of cloth-coated AgNPs was also confirmed, showing significant inhibition on both pathogens, and suggesting potential application in wound dressings and infection control. In addition, synthesized AgNPs exhibited high selectivity for L-cysteine hydrochloride among amino acids, indicating their utility as reliable colourimetric nanoprobes for cysteine detection. Furthermore, bioactive compounds in the crude and broth extracts were analysed using Orbitrap High-Resolution LC-MS, revealing major novel compounds including betaine, methylimidazoleacetic acid, L-norleucine, choline, DL-carnitine, hypoxanthine, hexadecanamide, and linoleoyl ethanolamide. This study opens a new avenue for the large-scale production of <em>C. molybdites</em> bioactive compounds, which may be valuable in future efforts to combat infections caused by MDR bacteria.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108205"},"PeriodicalIF":3.5,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615360","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 : 2025-11-25DOI: 10.1016/j.micpath.2025.108209
Jae-Yeon Park , Maheswaran Easwaran , Ju-Hun Kim , Hyun-Jin Shin
Rabies virus (RV) infection causes a fatal neurological disease affecting both animals, particularly canines, and humans. As a novel approach, canine Fc fusion protein into a recombinant RV may enhance both humoral and cellular-mediated immunity and is expected a promising strategy for vaccine development and therapeutic interventions. To enhance the immunogenicity of a traditional rabies vaccine, we generated a recombinant RV-expressing canine Fc fusion protein (RV-Fc) by cloning the RV-Fc fusion gene into the pcDNA3 vector and expressing the recombinant protein in Vero cells, yielding a protein of approximately 42 kDa. The expression of the recombinant RV-Fc protein was confirmed via immunocytochemistry and Western blot analysis. To evaluate the induction of immune responses such as antibody and cytokine production, we performed experiments using RV and RV-Fc immunized mice model. Serum neutralization (SN) assays demonstrated that cells treated with RV-Fc elicited higher antibody titers compared to cells treated with RV alone at week 1 post-treatment (p = 0.036). ELISA revealed a statistically significant increase in humoral immune responses in mice immunized with the RV-Fc vaccine compared to those immunized with the RV vaccine. This increase was observed for IgM at week 4 (p = 0.016), IgA at week 1 (p = 0.010), and IgG at both week 1 (p = 0.027) and week 4 (p = 0.006) post-immunization. Furthermore, analysis of cytokine levels demonstrated significant elevation in both IL-4 (p = 0.020) and IL-12 (p = 0.023) in the RV-Fc group relative to the RV group. Mice infected with RV-Fc exhibited enhanced humoral immune responses, as evidenced by increased levels of CD3 T cells (p = 0.039), B220/CD3 (B/T) cells (p = 0.018), and CD4 B cells (p = 0.044) compared to mice infected with RV alone. These findings suggest that the RV-CFc vaccine candidate holds promise for enhancing both cellular and humoral immune responses, potentially offering improved protection against rabies virus infection.
{"title":"Augmentation of humoral and cell-mediated immune responses by recombinant rabies virus expressing canine Fc","authors":"Jae-Yeon Park , Maheswaran Easwaran , Ju-Hun Kim , Hyun-Jin Shin","doi":"10.1016/j.micpath.2025.108209","DOIUrl":"10.1016/j.micpath.2025.108209","url":null,"abstract":"<div><div>Rabies virus (RV) infection causes a fatal neurological disease affecting both animals, particularly canines, and humans. As a novel approach, canine Fc fusion protein into a recombinant RV may enhance both humoral and cellular-mediated immunity and is expected a promising strategy for vaccine development and therapeutic interventions. To enhance the immunogenicity of a traditional rabies vaccine, we generated a recombinant RV-expressing canine Fc fusion protein (RV-Fc) by cloning the RV-Fc fusion gene into the pcDNA3 vector and expressing the recombinant protein in Vero cells, yielding a protein of approximately 42 kDa. The expression of the recombinant RV-Fc protein was confirmed via immunocytochemistry and Western blot analysis. To evaluate the induction of immune responses such as antibody and cytokine production, we performed experiments using RV and RV-Fc immunized mice model. Serum neutralization (SN) assays demonstrated that cells treated with RV-Fc elicited higher antibody titers compared to cells treated with RV alone at week 1 post-treatment (p = 0.036). ELISA revealed a statistically significant increase in humoral immune responses in mice immunized with the RV-Fc vaccine compared to those immunized with the RV vaccine. This increase was observed for IgM at week 4 (p = 0.016), IgA at week 1 (p = 0.010), and IgG at both week 1 (p = 0.027) and week 4 (p = 0.006) post-immunization. Furthermore, analysis of cytokine levels demonstrated significant elevation in both IL-4 (p = 0.020) and IL-12 (p = 0.023) in the RV-Fc group relative to the RV group. Mice infected with RV-Fc exhibited enhanced humoral immune responses, as evidenced by increased levels of CD3 T cells (p = 0.039), B220/CD3 (B/T) cells (p = 0.018), and CD4 B cells (p = 0.044) compared to mice infected with RV alone. These findings suggest that the RV-CFc vaccine candidate holds promise for enhancing both cellular and humoral immune responses, potentially offering improved protection against rabies virus infection.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108209"},"PeriodicalIF":3.5,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635883","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 : 2025-11-25DOI: 10.1016/j.micpath.2025.108204
Yanqiu Liang , Ruxiang Sheng , Yingqing Hu , Dingbang Huang , Xuan Li , Huan Deng , Dezhao Liu
Background
Intestinal ischemia-reperfusion (II/R) has an insidious onset but rapid progression, in which activation of intestinal immune cells and release of inflammatory factors play an important role. However, there is no clear therapeutic drug or method for II/R injury. Short-chain fatty acids (SCFAs) including propionate produced by the catabolism of intestinal flora have important intestinal protective effects and help prevent related diseases. This study aimed to investigate the protective effects of propionate (PR) in II/R injury.
Material and methods
A combination of bioinformatics and experimental validation was used to analyze the targets of propionate action on II/R injury. The effects of PR on mast cells were evaluated by analyzing the expression of inflammatory factors and trypsin, as well as flow cytometry. The effect of PR on II/R injury was evaluated by survival rate, histology, immunohistochemistry, immunofluorescence and TUNEL.
Results
PR can participate in the process of II/R injury through multiple targets. PR has a strong binding ability with Aryl hydrocarbon receptor (AhR)(-3.5 kcal/mol). In addition, PR inhibited the activation of mast cells during the II/R process by increasing the expression of AhR, thereby inhibiting the inflammatory response, reducing intestinal mucosal damage, and enhancing the expression of tight junction proteins, thereby alleviating II/R injury in mice.
Conclusions
This study demonstrated that PR, a metabolite of intestinal flora, inhibited mast cell activation by regulating the AhR-Notch1 pathway, thereby attenuating intestinal ischemia-reperfusion injury.
{"title":"Propionate intervenes mast cell function to alleviate intestinal ischemia-reperfusion injury by regulating AhR/Notch1 pathway","authors":"Yanqiu Liang , Ruxiang Sheng , Yingqing Hu , Dingbang Huang , Xuan Li , Huan Deng , Dezhao Liu","doi":"10.1016/j.micpath.2025.108204","DOIUrl":"10.1016/j.micpath.2025.108204","url":null,"abstract":"<div><h3>Background</h3><div>Intestinal ischemia-reperfusion (II/R) has an insidious onset but rapid progression, in which activation of intestinal immune cells and release of inflammatory factors play an important role. However, there is no clear therapeutic drug or method for II/R injury. Short-chain fatty acids (SCFAs) including propionate produced by the catabolism of intestinal flora have important intestinal protective effects and help prevent related diseases. This study aimed to investigate the protective effects of propionate (PR) in II/R injury.</div></div><div><h3>Material and methods</h3><div>A combination of bioinformatics and experimental validation was used to analyze the targets of propionate action on II/R injury. The effects of PR on mast cells were evaluated by analyzing the expression of inflammatory factors and trypsin, as well as flow cytometry. The effect of PR on II/R injury was evaluated by survival rate, histology, immunohistochemistry, immunofluorescence and TUNEL.</div></div><div><h3>Results</h3><div>PR can participate in the process of II/R injury through multiple targets. PR has a strong binding ability with Aryl hydrocarbon receptor (AhR)(-3.5 kcal/mol). In addition, PR inhibited the activation of mast cells during the II/R process by increasing the expression of AhR, thereby inhibiting the inflammatory response, reducing intestinal mucosal damage, and enhancing the expression of tight junction proteins, thereby alleviating II/R injury in mice.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that PR, a metabolite of intestinal flora, inhibited mast cell activation by regulating the AhR-Notch1 pathway, thereby attenuating intestinal ischemia-reperfusion injury.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108204"},"PeriodicalIF":3.5,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615361","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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