Microbial pathogenesis最新文献_第4页

Contribution of viable but non culturable cells and small colony variants in antibiotic insusceptibility and therapeutic failure against S. aureus and P. aeruginosa biofilm co-infections 对金黄色葡萄球菌和铜绿假单胞菌生物膜合并感染的抗生素不敏感和治疗失败的贡献，但不可培养的活细胞和小菌落变异

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-20 DOI: 10.1016/j.micpath.2026.108312

Andreia Patrícia Magalhães , Paula Jorge , Joana Neiva , Ana Margarida Sousa , Nuno Cerca , Maria Olívia Pereira

P. aeruginosa and S. aureus are often co-isolated from biofilm-associated infections, such as those afflicting cystic fibrosis (CF) patients. Biofilms, along with the interspecies interactions, play a significant role in fostering antibiotic insusceptibility, contributing to infection chronicity. Previously, we showed that S. aureus adopts a viable but non-culturable (VBNC) state in biofilms with P. aeruginosa. Here, we aimed to gain insight into the impact of VBNC and phenomena such as phenotypic switching on antimicrobial treatment and vice-versa. Single- and dual-species biofilms of two isolates from each species were characterised in terms of viability, culturability, clonal diversification, and pathogenic potential, upon treatment with ciprofloxacin and vancomycin. Data show that S. aureus became less susceptible to antibiotics in its VBNC state induced by P. aeruginosa and by the treatments. P. aeruginosa's susceptibility to ciprofloxacin diminished in dual-species biofilms, suggesting mutual benefits. Following treatment, S. aureus persisted as VBNC in the dual-species biofilm and its tolerance to ciprofloxacin endured after planktonic regrowth. P. aeruginosa triggered S. aureus's small colony variants (SCV), but P. aeruginosa's rugose SCV probably explains S. aureus's protection due to enhanced biofilm formation.

This work sheds light on P. aeruginosa and S. aureus' co-increased tolerance to antibiotics, with cooperative interactions, phenotypic diversification, and VBNC underpinning this and the persistence of S. aureus within P. aeruginosa biofilms. This work is the first relating S. aureus's decreased susceptibility in dual-species biofilms to its VBNC state. Findings highlight the importance of microbial ecology, viability and colony morphotyping studies when designing treatments for multispecies infections.

铜绿假单胞菌和金黄色葡萄球菌通常从生物膜相关感染中分离出来，如囊性纤维化（CF）患者。生物膜，连同种间的相互作用，在促进抗生素不敏感中起着重要作用，有助于感染的慢性。之前，我们发现金黄色葡萄球菌在铜绿假单胞菌的生物膜中采用了一种可存活但不可培养（VBNC）的状态。在这里，我们的目的是深入了解VBNC和表型转换等现象对抗菌药物治疗的影响，反之亦然。在环丙沙星和万古霉素处理下，从每个物种分离的两株菌株的单种和双种生物膜在活力、培养能力、克隆多样化和致病潜力方面进行了表征。数据显示，在铜绿假单胞菌诱导的VBNC状态下，金黄色葡萄球菌对抗生素的敏感性降低。铜绿假单胞菌对环丙沙星的敏感性在双种生物膜中降低，表明互惠互利。经过处理后，金黄色葡萄球菌在双种生物膜中以VBNC的形式存在，浮游再生后其对环丙沙星的耐受性持续存在。铜绿假单胞菌引发了金黄色葡萄球菌的小菌落变异（SCV），但铜绿假单胞菌的rugose SCV可能解释了金黄色葡萄球菌由于加强生物膜形成而具有保护作用。这项工作揭示了铜绿假单胞菌和金黄色葡萄球菌共同增加对抗生素的耐受性，合作相互作用、表型多样化和VBNC支持了这一点，以及金黄色葡萄球菌在铜绿假单胞菌生物膜内的持久性。这项工作是第一次将金黄色葡萄球菌在双种生物膜中对其VBNC状态的敏感性降低联系起来。研究结果强调了微生物生态学、生存能力和菌落形态分型研究在设计多物种感染治疗方案时的重要性。

{"title":"Contribution of viable but non culturable cells and small colony variants in antibiotic insusceptibility and therapeutic failure against S. aureus and P. aeruginosa biofilm co-infections","authors":"Andreia Patrícia Magalhães , Paula Jorge , Joana Neiva , Ana Margarida Sousa , Nuno Cerca , Maria Olívia Pereira","doi":"10.1016/j.micpath.2026.108312","DOIUrl":"10.1016/j.micpath.2026.108312","url":null,"abstract":"<div><div>P. aeruginosa and <em>S. aureus</em> are often co-isolated from biofilm-associated infections, such as those afflicting cystic fibrosis (CF) patients. Biofilms, along with the interspecies interactions, play a significant role in fostering antibiotic insusceptibility, contributing to infection chronicity. Previously, we showed that <em>S. aureus</em> adopts a viable but non-culturable (VBNC) state in biofilms with <em>P. aeruginosa</em>. Here, we aimed to gain insight into the impact of VBNC and phenomena such as phenotypic switching on antimicrobial treatment and vice-versa. Single- and dual-species biofilms of two isolates from each species were characterised in terms of viability, culturability, clonal diversification, and pathogenic potential, upon treatment with ciprofloxacin and vancomycin. Data show that <em>S. aureus</em> became less susceptible to antibiotics in its VBNC state induced by <em>P. aeruginosa</em> and by the treatments. <em>P. aeruginosa</em>'s susceptibility to ciprofloxacin diminished in dual-species biofilms, suggesting mutual benefits. Following treatment, <em>S. aureus</em> persisted as VBNC in the dual-species biofilm and its tolerance to ciprofloxacin endured after planktonic regrowth. <em>P. aeruginosa</em> triggered <em>S. aureus</em>'s small colony variants (SCV), but <em>P. aeruginosa's</em> rugose SCV probably explains <em>S. aureus</em>'s protection due to enhanced biofilm formation.</div><div>This work sheds light on <em>P. aeruginosa</em> and <em>S. aureus</em>' co-increased tolerance to antibiotics, with cooperative interactions, phenotypic diversification, and VBNC underpinning this and the persistence of <em>S. aureus</em> within <em>P. aeruginosa</em> biofilms. This work is the first relating <em>S. aureus</em>'s decreased susceptibility in dual-species biofilms to its VBNC state. Findings highlight the importance of microbial ecology, viability and colony morphotyping studies when designing treatments for multispecies infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108312"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023720","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}

引用次数: 0

EA mitigates sepsis-induced liver injury by inhibiting the proinflammatory pathways IκBα/NF-κB and NLRP3-mediated pyroptosis EA通过抑制促炎通路IκBα/NF-κB和nlrp3介导的焦亡来减轻败血症诱导的肝损伤

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 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":"2026-03-01","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}

引用次数: 0

In vitro and in vivo evaluation of antibacterial activity of 1,8-cineol and the essential oil of Myrciaria pilosa Sobral & Couto 1,8-桉树油酚与桃金娘挥发油体外、体内抑菌活性评价

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 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.

寻找具有抗菌活性的新药是全球的当务之急。因此，本研究旨在研究桃金娘叶精油（EOMP）及其主要化合物1,8-桉树脑（CNL）对耐药菌的抑菌和调控作用。因此，通过加氢蒸馏得到初始EOMP，并通过气相色谱分析，鉴定出CNL为主要化合物（34.51 %）。最低抑菌浓度（MIC）试验对环境和临床来源的耐药细菌分离株进行。结果表明，EOMP和CNL与氨苄西林（AMP）联合使用可显著降低MIC值，对施莱氏葡萄球菌、溶血葡萄球菌、金黄色葡萄球菌和产氧克雷伯菌的FICI值在0.005 ~ 1.0之间。生长曲线和细菌杀灭时间分析结果显示，与未经处理的菌株相比，氧化克雷伯菌和溶血克雷伯菌的细菌负荷下降幅度更大。对于含有黄粉虫的体内模型，这些处理没有显示出毒性作用，并且在前24 h内有效保护幼虫免受耐药菌感染。这些发现是首次报道EOMP与AMP的协同活性，以及其体内有效性，并加强了精油在对抗细菌耐药性方面的协同潜力。

{"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":"2026-03-01","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}

引用次数: 0

A novel Escherichia phage against multidrug-resistant hybrid IPEC/ExPEC Escherichia coli 一种抗多药耐药杂交IPEC/ exic大肠杆菌的新型噬菌体。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.micpath.2026.108308

Napakhwan Imklin , Kotryna Kvederavičiūtė , Wanchana Aesomnuk , Siwaret Arikit , Pornchalit Assavacheep , Eugenijus Šimoliūnas , Rujikan Nasanit

Aims

In this work, Escherichia coli isolates from pig specimens were investigated for their virulence and drug-resistant profiles. Escherichia phage nasanit was isolated, characterized, and assessed its lytic activity against its host.

Methods and results

All tested E. coli isolates were identified as multidrug-resistant hybrid intestinal pathogenic E. coli/extraintestinal pathogenic E. coli (IPEC/ExPEC). The phage exhibited infectivity against E. coli isolates from porcine and bovine specimens by spot testing. Lytic activity assays against its host in simulated intestinal fluid at 39 °C and tryptic soy broth at 30 °C demonstrated a significant reduction in bacterial density at 30 °C. Genomic analysis confirmed the absence of undesirable genes, and comparative genomic analysis suggested that the phage constitutes a novel species within the Berlinvirus genus.

Conclusion

Escherichia phage nasanit demonstrates potential as a biosanitizing agent for mitigating livestock-associated colibacillosis in swine environments.

Impact statement

E. coli isolates harbored both IPEC and ExPEC virulence genes, coupled with a multidrug resistance, posing a significant risk for diverse disease in swine. Escherichia phage nasanit demonstrated lytic activity against pathogenic E. coli associated with swine and bovine diseases. The phage efficacy in eliminating the tested E. coli suggests its potential application for biosanitation in the swine industry.

目的：研究猪分离的大肠杆菌的毒力和耐药谱。分离了纳氏噬菌体，对其进行了鉴定，并评价了其对宿主的裂解活性。方法与结果：所有大肠杆菌分离株均鉴定为多重耐药肠道致病性大肠杆菌/肠外致病性大肠杆菌（IPEC/ExPEC）。通过现场检测，该噬菌体对猪和牛的大肠杆菌分离株具有感染性。在39°C的模拟肠液和30°C的胰蛋白酶豆汤中对其宿主的裂解活性测定表明，在30°C时细菌密度显著降低。基因组分析证实不存在不良基因，比较基因组分析表明该噬菌体构成柏林病毒属的一个新种。结论：噬菌体大肠杆菌显示了作为生物消毒剂在猪环境中减轻家畜相关大肠杆菌病的潜力。影响声明：大肠杆菌分离物同时携带IPEC和ExPEC毒力基因，加上多药耐药性，对猪的多种疾病构成重大风险。大肠杆菌噬菌体对与猪和牛疾病相关的致病性大肠杆菌具有裂解活性。噬菌体清除大肠杆菌的效果表明其在养猪业生物卫生方面的潜在应用。

{"title":"A novel Escherichia phage against multidrug-resistant hybrid IPEC/ExPEC Escherichia coli","authors":"Napakhwan Imklin , Kotryna Kvederavičiūtė , Wanchana Aesomnuk , Siwaret Arikit , Pornchalit Assavacheep , Eugenijus Šimoliūnas , Rujikan Nasanit","doi":"10.1016/j.micpath.2026.108308","DOIUrl":"10.1016/j.micpath.2026.108308","url":null,"abstract":"<div><h3>Aims</h3><div>In this work, <em>Escherichia coli</em> isolates from pig specimens were investigated for their virulence and drug-resistant profiles. <em>Escherichia</em> phage nasanit was isolated, characterized, and assessed its lytic activity against its host.</div></div><div><h3>Methods and results</h3><div>All tested <em>E. coli</em> isolates were identified as multidrug-resistant hybrid intestinal pathogenic <em>E. coli</em>/extraintestinal pathogenic <em>E. coli</em> (IPEC/ExPEC). The phage exhibited infectivity against <em>E. coli</em> isolates from porcine and bovine specimens by spot testing. Lytic activity assays against its host in simulated intestinal fluid at 39 °C and tryptic soy broth at 30 °C demonstrated a significant reduction in bacterial density at 30 °C. Genomic analysis confirmed the absence of undesirable genes, and comparative genomic analysis suggested that the phage constitutes a novel species within the <em>Berlinvirus</em> genus.</div></div><div><h3>Conclusion</h3><div><em>Escherichia</em> phage nasanit demonstrates potential as a biosanitizing agent for mitigating livestock-associated colibacillosis in swine environments.</div></div><div><h3>Impact statement</h3><div><em>E. coli</em> isolates harbored both IPEC and ExPEC virulence genes, coupled with a multidrug resistance, posing a significant risk for diverse disease in swine. <em>Escherichia</em> phage nasanit demonstrated lytic activity against pathogenic <em>E. coli</em> associated with swine and bovine diseases. The phage efficacy in eliminating the tested <em>E. coli</em> suggests its potential application for biosanitation in the swine industry.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108308"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018709","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}

引用次数: 0

Production of two Kımı pickles using the whey and vinegar as fermentation media and determination of bacterial and fungal microbiota, antibacterial and antibiofilm activities of Kımı pickles 以乳清和醋为发酵介质生产两种Kımı泡菜及Kımı泡菜细菌和真菌菌群、抗菌和抗膜活性的测定

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-18 DOI: 10.1016/j.micpath.2026.108306

Damla Adsız , Nurcan Erbil , Ahmet İlçim

Plants can be used for different purposes, such as food, tea, and spices or for healing against various diseases. In this study, two different Kımı pickles, such as fermented with vinegar (SKT) and fermented with whey (PASKT), were produced. The antibacterial properties of both Kımı pickles were determined by MIC, MBC, and MTC and antibiofilm activity was determined by the crystal violet method. The bacterial microbiota of the Kımı pickle samples were determined by 16S metagenom analysis and the fungal microbiota by ITS metagenom analysis. As a result, the plant known as Kımı was systematically determined as Bunium cylindricum (Boiss. & Hohem.) Drude. PASKT exhibited the highest antibacterial activity against Bacillus licheniformis ATCC 14580, Klebsiella pneumoniae ATCC 33495, and Staphylococcus aureus ATCC 6538, while Staphylococcus aureus ATCC 6538 was the most sensitive to SKT. PASKT inhibited biofilm formation at a higher rate against Escherichia coli ATCC 8739 and Bacillus licheniformis ATCC 14580, while SKT exhibited higher antibiofilm activity against Klebsiella pneumoniae ATCC 33495 and Bacillus licheniformis ATCC 14580. The dominant bacterial genus in the PASKT was Bacteroides, whereas in the SKT it was Latilactobacillus. Dipodascus was the dominant genus in the PASKT fungal microbiota, while Penicillium was the dominant genus in the SKT fungal microbiota. In this study, whey was used as the fermentation medium for PASKT production. This has the potential to create an alternative for the utilization of whey, which is rich in nutrient content but is considered waste and can cause environmental pollution.

植物可以有不同的用途，如食物、茶和香料，或用于治疗各种疾病。在本研究中，生产了两种不同的Kımı泡菜，如醋发酵（SKT）和乳清发酵（PASKT）。采用MIC法、MBC法和MTC法测定Kımı酸菜的抗菌性能，并用结晶紫法测定抗菌膜活性。采用16S宏宏分析和ITS宏宏分析分别测定Kımı泡菜样品的细菌菌群和真菌菌群。结果，被称为Kımı的植物被系统地确定为白筒菇(Boiss。& Hohem)。柯克。PASKT对地衣芽孢杆菌ATCC 14580、肺炎克雷伯菌ATCC 33495和金黄色葡萄球菌ATCC 6538的抑菌活性最高，而金黄色葡萄球菌ATCC 6538对SKT最敏感。PASKT对大肠杆菌ATCC 8739和地衣芽孢杆菌ATCC 14580的生物膜形成抑制率较高，而SKT对肺炎克雷伯菌ATCC 33495和地衣芽孢杆菌ATCC 14580的生物膜形成抑制率较高。PASKT的优势菌属为拟杆菌属，SKT的优势菌属为乳酸杆菌属。在PASKT真菌菌群中，双足霉属为优势属，而在SKT真菌菌群中，青霉属为优势属。本研究以乳清为发酵培养基生产PASKT。这有可能为乳清的利用创造一种替代方案，乳清富含营养成分，但被认为是废物，并可能造成环境污染。

{"title":"Production of two Kımı pickles using the whey and vinegar as fermentation media and determination of bacterial and fungal microbiota, antibacterial and antibiofilm activities of Kımı pickles","authors":"Damla Adsız , Nurcan Erbil , Ahmet İlçim","doi":"10.1016/j.micpath.2026.108306","DOIUrl":"10.1016/j.micpath.2026.108306","url":null,"abstract":"<div><div>Plants can be used for different purposes, such as food, tea, and spices or for healing against various diseases. In this study, two different Kımı pickles, such as fermented with vinegar (SKT) and fermented with whey (PASKT), were produced. The antibacterial properties of both Kımı pickles were determined by MIC, MBC, and MTC and antibiofilm activity was determined by the crystal violet method. The bacterial microbiota of the Kımı pickle samples were determined by 16S metagenom analysis and the fungal microbiota by ITS metagenom analysis. As a result, the plant known as Kımı was systematically determined as <em>Bunium cylindricum</em> (Boiss. & Hohem.) Drude. PASKT exhibited the highest antibacterial activity against <em>Bacillus licheniformis</em> ATCC 14580, <em>Klebsiella pneumoniae</em> ATCC 33495, and <em>Staphylococcus aureus</em> ATCC 6538, while <em>Staphylococcus aureus</em> ATCC 6538 was the most sensitive to SKT. PASKT inhibited biofilm formation at a higher rate against <em>Escherichia coli</em> ATCC 8739 and <em>Bacillus licheniformis</em> ATCC 14580, while SKT exhibited higher antibiofilm activity against <em>Klebsiella pneumoniae</em> ATCC 33495 and <em>Bacillus licheniformis</em> ATCC 14580. The dominant bacterial genus in the PASKT was <em>Bacteroides</em>, whereas in the SKT it was <em>Latilactobacillus</em>. <em>Dipodascus</em> was the dominant genus in the PASKT fungal microbiota, while <em>Penicillium</em> was the dominant genus in the SKT fungal microbiota. In this study, whey was used as the fermentation medium for PASKT production. This has the potential to create an alternative for the utilization of whey, which is rich in nutrient content but is considered waste and can cause environmental pollution.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108306"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011280","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}

引用次数: 0

Engineering of polymers decorated bimetallic nanoparticles improves bacterial cuproptosis death in acute lung injury and pediatric severe pneumonia 聚合物修饰的双金属纳米颗粒工程改善急性肺损伤和儿童重症肺炎的细菌性铜中毒死亡。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2025-12-18 DOI: 10.1016/j.micpath.2025.108248

Xiao Ma, Ge Shi

Pediatric severe pneumonia represents a significant global infectious illness, characterized by elevated morbidity and mortality rates. In light of antibiotic misuse and bacterial biofilm resistance, various metal-based compounds have been established. Nevertheless, the elevated oxygen levels in the lungs enable certain aerobic pathogenic bacteria to exhibit significant tolerance to oxygen and reactive oxygen species (ROS), rendering metal-based materials reliant on ROS potentially ineffective in therapeutic applications. Motivated by the susceptibility to cuproptosis in aerobic respiratory cells, we developed an antibacterial copper nanocomposite. We demonstrated that it can efficiently induce cuproptosis-like mortality in the lungs of aerobic bacteria. To overcome the challenges of in vivo cuproptosis, manganese dioxide was initially used to reduce protective glutathione, which binds copper and thereby prevents its interaction with proteins, thereby facilitating antibacterial action through immunological improvement. Cuproptosis-like cell death necessitates a substantial quantity of copper ions. To satisfy this demand, we provide positively hydrophilic altered CM nanoparticles that efficiently traverse the lung mucus layer via local administration, with copper ions subsequently released rapidly by the acidic conditions at the infection site, thereby enhancing the destruction of bacterial biofilms in conjunction with manganese. This drug-delivery method can efficiently address pediatric severe pneumonia, while mitigating systemic toxicity associated with high dosages of copper.

儿童重症肺炎是一种重要的全球性传染病，其特点是发病率和死亡率高。鉴于抗生素的滥用和细菌的生物膜耐药性，各种金属基化合物已经建立。然而，肺中氧水平的升高使某些需氧致病菌对氧和活性氧（ROS）表现出显著的耐受性，使得依赖ROS的金属基材料在治疗应用中可能无效。基于有氧呼吸细胞对铜腐蚀的敏感性，我们开发了一种抗菌铜纳米复合材料。我们证明了它可以有效地诱导需氧细菌肺部的铜腐病样死亡。为了克服体内铜还原的挑战，二氧化锰最初被用来减少保护性谷胱甘肽，它与铜结合，从而阻止其与蛋白质的相互作用，从而通过免疫改善促进抗菌作用。铜中毒样细胞死亡需要大量的铜离子。为了满足这一需求，我们提供了正亲水性改变的CM纳米颗粒，通过局部给药有效地穿过肺黏液层，随后在感染部位的酸性条件下迅速释放铜离子，从而增强了与锰一起破坏细菌生物膜的能力。这种给药方法可以有效地治疗小儿重症肺炎，同时减轻与高剂量铜相关的全身毒性。

{"title":"Engineering of polymers decorated bimetallic nanoparticles improves bacterial cuproptosis death in acute lung injury and pediatric severe pneumonia","authors":"Xiao Ma, Ge Shi","doi":"10.1016/j.micpath.2025.108248","DOIUrl":"10.1016/j.micpath.2025.108248","url":null,"abstract":"<div><div>Pediatric severe pneumonia represents a significant global infectious illness, characterized by elevated morbidity and mortality rates. In light of antibiotic misuse and bacterial biofilm resistance, various metal-based compounds have been established. Nevertheless, the elevated oxygen levels in the lungs enable certain aerobic pathogenic bacteria to exhibit significant tolerance to oxygen and reactive oxygen species (ROS), rendering metal-based materials reliant on ROS potentially ineffective in therapeutic applications. Motivated by the susceptibility to cuproptosis in aerobic respiratory cells, we developed an antibacterial copper nanocomposite. We demonstrated that it can efficiently induce cuproptosis-like mortality in the lungs of aerobic bacteria. To overcome the challenges of in vivo cuproptosis, manganese dioxide was initially used to reduce protective glutathione, which binds copper and thereby prevents its interaction with proteins, thereby facilitating antibacterial action through immunological improvement. Cuproptosis-like cell death necessitates a substantial quantity of copper ions. To satisfy this demand, we provide positively hydrophilic altered CM nanoparticles that efficiently traverse the lung mucus layer via local administration, with copper ions subsequently released rapidly by the acidic conditions at the infection site, thereby enhancing the destruction of bacterial biofilms in conjunction with manganese. This drug-delivery method can efficiently address pediatric severe pneumonia, while mitigating systemic toxicity associated with high dosages of copper.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108248"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800596","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}

引用次数: 0

Salvia abrotanoides leaves and flowers essential oils inhibit the quorum-sensing system of extensively drug-resistant (XDR) Acinetobacter baumannii 丹参叶和花精油对广泛耐药鲍曼不动杆菌群体感应系统的抑制作用。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2025-12-19 DOI: 10.1016/j.micpath.2025.108256

Mohammad Hadi Masoomi, Matia Sadat Borhani, Mahmood Salehi, Sohrab Boozarpour, Meisam Habibi

Bacteremia, meningitis, endocarditis, and pneumonia are some difficult-to-treat nosocomial infections caused by drug-resistant Acinetobacter baumannii. This study aimed to investigate Salvia abrotanoides essential oils against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of A. baumannii, which have not previously been reported. Essential oils extracted from Salvia abrotanoides leaf (L. EO) and flower (F. EO) were analyzed for the antimicrobial, antioxidant, and cell cytotoxicity activity. GC/MS identified 19 new compounds not previously reported in the studied EOs. The IC50 values from the DPPH assay were 0.22 mg/mL for L. EO and 0.015 mg/mL for F. EO. The essential oils showed antimicrobial activity, with concentrations ranging from 1.4 to 1.75 mg/mL for MIC and from 2.8 to 7 mg/mL for MBC, effectively inhibiting growth and killing the tested MDR and XDR strains, respectively. Furthermore, at sub-MIC concentrations, both essential oils downregulated the expression of several key genes in A. baumannii, including bap, csuD, abaI, abaR, and barB, based on qRT-PCR results. ADMET analysis demonstrated that all studied plant ligands complied with Lipinski's rule of five and Veber's rule, indicating their potential as oral bioavailable drugs. Based on these findings, the essential oils of S. abrotanoides (F. EO and L. EO) are promising for the development of antimicrobial agents targeting the MDR and XDR strains of A. baumannii.

菌血症、脑膜炎、心内膜炎和肺炎是耐药鲍曼不动杆菌引起的一些难以治疗的院内感染。本研究旨在探讨丹参精油对鲍曼不动杆菌多重耐药（MDR）和广泛耐药（XDR）菌株的拮抗作用，这两种菌株此前未见报道。以丹参叶（L. EO）和花（F. EO）为原料，对其抑菌活性、抗氧化活性和细胞毒性进行了研究。GC/MS鉴定出19个未在研究的EOs中报道的新化合物。L. EO和F. EO的IC50分别为0.22 mg/mL和0.015 mg/mL。精油的抑菌活性为MIC浓度为1.4 ~ 1.75 mg/mL， MBC浓度为2.8 ~ 7 mg/mL，分别能有效抑制MDR和XDR菌株的生长和杀伤。此外，根据qRT-PCR结果，在亚mic浓度下，这两种精油都下调了鲍曼不饱和杆菌中几个关键基因的表达，包括bap、csuD、abaI、abaR和barB。ADMET分析表明，所研究的植物配体均符合Lipinski的五法则和Veber的法则，表明它们具有作为口服生物利用药物的潜力。综上所述，该植物精油（f.o o和l.o o）具有开发针对鲍曼不动杆菌MDR和XDR菌株的抗菌药物的潜力。

{"title":"Salvia abrotanoides leaves and flowers essential oils inhibit the quorum-sensing system of extensively drug-resistant (XDR) Acinetobacter baumannii","authors":"Mohammad Hadi Masoomi, Matia Sadat Borhani, Mahmood Salehi, Sohrab Boozarpour, Meisam Habibi","doi":"10.1016/j.micpath.2025.108256","DOIUrl":"10.1016/j.micpath.2025.108256","url":null,"abstract":"<div><div>Bacteremia, meningitis, endocarditis, and pneumonia are some difficult-to-treat nosocomial infections caused by drug-resistant <em>Acinetobacter baumannii</em>. This study aimed to investigate <em>Salvia abrotanoides</em> essential oils against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of <em>A. baumannii</em>, which have not previously been reported. Essential oils extracted from <em>Salvia abrotanoides</em> leaf (L. EO) and flower (F. EO) were analyzed for the antimicrobial, antioxidant, and cell cytotoxicity activity. GC/MS identified 19 new compounds not previously reported in the studied EOs. The IC50 values from the DPPH assay were 0.22 mg/mL for L. EO and 0.015 mg/mL for F. EO. The essential oils showed antimicrobial activity, with concentrations ranging from 1.4 to 1.75 mg/mL for MIC and from 2.8 to 7 mg/mL for MBC, effectively inhibiting growth and killing the tested MDR and XDR strains, respectively. Furthermore, at sub-MIC concentrations, both essential oils downregulated the expression of several key genes in <em>A. baumannii</em>, including <em>bap</em>, <em>csuD</em>, <em>abaI</em>, <em>abaR</em>, and <em>barB</em>, based on qRT-PCR results. ADMET analysis demonstrated that all studied plant ligands complied with Lipinski's rule of five and Veber's rule, indicating their potential as oral bioavailable drugs. Based on these findings, the essential oils of <em>S. abrotanoides</em> (F. EO and L. EO) are promising for the development of antimicrobial agents targeting the MDR and XDR strains of <em>A. baumannii</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108256"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805046","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}

引用次数: 0

Maxing Shigan decoction serves as a key component of Lianhua Qingwen in alleviating lung and gut injury by restoring gut microbiota homeostasis and inhibiting inflammation via TLR4/NF-κB and JAK2/STAT3 dual regulation 麻杏石肝汤通过TLR4/NF-κB和JAK2/STAT3双调控恢复肠道菌群稳态，抑制炎症，是连花清文减轻肺、肠损伤的关键成分。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.micpath.2026.108285

Caiyun Yuan , Peipei Jin , Zhuo He , Jing Guo , Mingyu Xiong , Jiemeng Sun , Le Wang , Zixuan Wang , Ningxin Han , Wei Feng , Yunlong Hou , Hui Qi , Zhenhua Jia

Lianhua Qingwen (LHQW), a clinically validated herbal medicine containing Maxing Shigan Decoction (MXSGT) and others, shows broad efficacy in various respiratory disease. However, its regulatory role on the gut-lung axis, particularly the contribution of its MXSGT components, remains unexplored. This study employed a formula-disassembled approach to decipher this mechanism. Three preparations, including the complete LHQW prescription, LHQW excluding MXSGT components (LHQW-MXSGT), and MXSGT along, were administered to LPS-induced acute lung injury and DSS-induced ulcerative colitis to evaluate their therapeutic effects via the gut-lung axis. Pathological changes, mucosal barrier integrity, inflammatory cell infiltration and pro-inflammatory cytokine levels were evaluated by H&E staining, histochemical staining, immunofluorescence, ELISA, RT-qPCR and Western blot. Metagenomic analysis (16S rDNA sequencing) was conducted to examine their regulatory role of gut microbiota. Network pharmacology analysis and cellular validation was employed to explore their underlying mechanisms. Our analyses demonstrated that LHQW and MXSGT, but not LHQW-MXSGT, significantly attenuated lung/intestinal pathology damage, reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored gut barrier proteins (ZO-1, Occludin, MUC2). LHQW/MXSGT suppressed pathogenic bacteria (Escherichia coli, Salmonella, Klebsiella pneumoniae) while enriching Akkermansia muciniphila, correlating with decreased systemic LPS. Network pharmacology and subsequent validation identified dual inhibition of TLR4/NF-κB and JAK2/STAT3 pathways as key mechanism of MXSGT.

In conclusion, MXSGT serves a pivotal pharmacologically active component of LHQW for its gut-lung axis regulation, acting through gut microbiota homeostasis restoration, intestinal barrier integrity maintenance, and anti-inflammatory signaling pathways, providing compelling scientific evidence supporting LHQW's potential therapeutic application in managing diseases characterized by comorbid gut and lung inflammation.

连花清温（LHQW）是一种经临床验证的中草药，含有麻杏石肝汤（MXSGT）等，对各种呼吸系统疾病有广泛的疗效。然而，其对肠-肺轴的调节作用，特别是其MXSGT成分的贡献，仍未被探索。本研究采用公式分解的方法来解读这一机制。采用LHQW全方、LHQW不含MXSGT成分（LHQW-MXSGT）和MXSGT加药3种制剂，经肠-肺轴观察其对lps诱导的急性肺损伤和dss诱导的溃疡性结肠炎的治疗效果。采用H&E染色、组织化学染色、免疫荧光、ELISA、RT-qPCR、western blot检测病理改变、黏膜屏障完整性、炎性细胞浸润及促炎细胞因子水平。宏基因组分析（16S rDNA测序）研究了它们在肠道微生物群中的调节作用。通过网络药理学分析和细胞验证来探讨其潜在机制。我们的分析表明，LHQW和MXSGT，而不是LHQW-MXSGT，显著减轻了肺/肠道病理损伤，降低了促炎细胞因子（TNF-α, IL-1β, IL-6），恢复了肠道屏障蛋白（ZO-1, Occludin, MUC2）。LHQW/MXSGT抑制致病菌（大肠杆菌、沙门氏菌、肺炎克雷伯菌），同时富集嗜粘液阿克曼氏菌，与降低全身LPS相关。网络药理学和随后的验证发现TLR4/NF-κB和JAK2/STAT3通路的双重抑制是MXSGT的关键机制。综上所述，MXSGT是LHQW调节肠-肺轴的关键药理活性成分，通过恢复肠道微生物群稳态、维持肠道屏障完整性和抗炎信号通路起作用，为LHQW在治疗以肠道和肺部共病为特征的疾病方面的潜在治疗应用提供了令人信服的科学证据。

{"title":"Maxing Shigan decoction serves as a key component of Lianhua Qingwen in alleviating lung and gut injury by restoring gut microbiota homeostasis and inhibiting inflammation via TLR4/NF-κB and JAK2/STAT3 dual regulation","authors":"Caiyun Yuan , Peipei Jin , Zhuo He , Jing Guo , Mingyu Xiong , Jiemeng Sun , Le Wang , Zixuan Wang , Ningxin Han , Wei Feng , Yunlong Hou , Hui Qi , Zhenhua Jia","doi":"10.1016/j.micpath.2026.108285","DOIUrl":"10.1016/j.micpath.2026.108285","url":null,"abstract":"<div><div>Lianhua Qingwen (LHQW), a clinically validated herbal medicine containing Maxing Shigan Decoction (MXSGT) and others, shows broad efficacy in various respiratory disease. However, its regulatory role on the gut-lung axis, particularly the contribution of its MXSGT components, remains unexplored. This study employed a formula-disassembled approach to decipher this mechanism. Three preparations, including the complete LHQW prescription, LHQW excluding MXSGT components (LHQW-MXSGT), and MXSGT along, were administered to LPS-induced acute lung injury and DSS-induced ulcerative colitis to evaluate their therapeutic effects via the gut-lung axis. Pathological changes, mucosal barrier integrity, inflammatory cell infiltration and pro-inflammatory cytokine levels were evaluated by H&E staining, histochemical staining, immunofluorescence, ELISA, RT-qPCR and Western blot. Metagenomic analysis (16S rDNA sequencing) was conducted to examine their regulatory role of gut microbiota. Network pharmacology analysis and cellular validation was employed to explore their underlying mechanisms. Our analyses demonstrated that LHQW and MXSGT, but not LHQW-MXSGT, significantly attenuated lung/intestinal pathology damage, reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored gut barrier proteins (ZO-1, Occludin, MUC2). LHQW/MXSGT suppressed pathogenic bacteria (<em>Escherichia coli, Salmonella, Klebsiella pneumoniae</em>) while enriching <em>Akkermansia muciniphila</em>, correlating with decreased systemic LPS. Network pharmacology and subsequent validation identified dual inhibition of TLR4/NF-κB and JAK2/STAT3 pathways as key mechanism of MXSGT.</div><div>In conclusion, MXSGT serves a pivotal pharmacologically active component of LHQW for its gut-lung axis regulation, acting through gut microbiota homeostasis restoration, intestinal barrier integrity maintenance, and anti-inflammatory signaling pathways, providing compelling scientific evidence supporting LHQW's potential therapeutic application in managing diseases characterized by comorbid gut and lung inflammation.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108285"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018796","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}

引用次数: 0

The Type 6 Secretion System (T6SS) plays a role in the pathogenesis of strain NMEC15 6型分泌系统（T6SS）在菌株NMEC15的发病机制中起作用

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.micpath.2026.108282

Aline L. de Oliveira , Julia Ienes-Lima , Nicolle L. Barbieri , Darby M. Newman , Meaghan M. Young , Lisa K. Nolan , Catherine M. Logue

Neonatal meningitis Escherichia coli (NMEC) is the second leading cause of sepsis and meningitis in newborns with fatality rates of 15–40 %. Survivors may suffer lifelong neurological sequelae such as cerebral palsy, seizures, hearing loss, and delayed development. Despite identification of virulence factors contributing to meningitis, the pathogenesis of NMEC remains to be elucidated. The Type 6 secretion system (T6SS) has been identified in the type strain NMEC RS218 and its associated Hcp proteins were shown to play a role in invasion, cytoskeleton rearrangement, and apoptosis of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier (BBB). The aim of this study was to assess T6SS prevalence in a collection of NMEC and characterize the T6SS in NMEC 15.

Here, we analyzed the prevalence of selected T6SS genes hcp, impK, evpB, vasK, and icmF in a collection of NMEC and their potential role in the adhesion and invasion of HBMEC and the differentiated macrophage cell line THP-1, and resistance to Dictyostelium discoideum predation by NMEC15. We show that ImpK and IcmF are involved in NMEC 15's adherence to HBMEC, and Hcp, ImpK, and IcmF are involved in invasion. The amoeba D. discoideum was used to demonstrate functionality of the T6SS with greater numbers of amoeba required to kill the WT NMEC15 compared to the hcp deletion mutant.

These studies provide further evidence of the potential role of T6SS in NMEC pathogenesis.

新生儿脑膜炎大肠杆菌（NMEC）是新生儿败血症和脑膜炎的第二大原因，死亡率为15 - 40%。幸存者可能遭受终身神经系统后遗症，如脑瘫、癫痫发作、听力丧失和发育迟缓。尽管确定了导致脑膜炎的毒力因素，但NMEC的发病机制仍有待阐明。在NMEC RS218型菌株中发现了6型分泌系统（T6SS），其相关Hcp蛋白在构成血脑屏障（BBB）的人脑微血管内皮细胞（HBMEC）的侵袭、细胞骨架重排和凋亡中发挥作用。本研究的目的是评估NMEC中T6SS的患病率，并描述NMEC 15中T6SS的特征。在这里，我们分析了选定的T6SS基因hcp、impK、evpB、vasK和icmF在一组NMEC中的流行情况，以及它们在HBMEC和分化的巨噬细胞系THP-1的粘附和侵袭以及NMEC15对盘状盘状盘状体捕食的抗性中的潜在作用。我们发现ImpK和IcmF参与了NMEC 15对HBMEC的粘附，Hcp、ImpK和IcmF参与了入侵。与hcp缺失突变体相比，使用变形虫D. discoideum来证明T6SS的功能，杀死WT NMEC15所需的变形虫数量更多。这些研究进一步证明了T6SS在NMEC发病机制中的潜在作用。

{"title":"The Type 6 Secretion System (T6SS) plays a role in the pathogenesis of strain NMEC15","authors":"Aline L. de Oliveira , Julia Ienes-Lima , Nicolle L. Barbieri , Darby M. Newman , Meaghan M. Young , Lisa K. Nolan , Catherine M. Logue","doi":"10.1016/j.micpath.2026.108282","DOIUrl":"10.1016/j.micpath.2026.108282","url":null,"abstract":"<div><div>Neonatal meningitis <em>Escherichia coli</em> (NMEC) is the second leading cause of sepsis and meningitis in newborns with fatality rates of 15–40 %. Survivors may suffer lifelong neurological sequelae such as cerebral palsy, seizures, hearing loss, and delayed development. Despite identification of virulence factors contributing to meningitis, the pathogenesis of NMEC remains to be elucidated. The Type 6 secretion system (T6SS) has been identified in the type strain NMEC RS218 and its associated Hcp proteins were shown to play a role in invasion, cytoskeleton rearrangement, and apoptosis of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier (BBB). The aim of this study was to assess T6SS prevalence in a collection of NMEC and characterize the T6SS in NMEC 15.</div><div>Here, we analyzed the prevalence of selected T6SS genes <em>hcp</em>, <em>impK</em>, <em>evpB</em>, <em>vasK,</em> and <em>icmF</em> in a collection of NMEC and their potential role in the adhesion and invasion of HBMEC and the differentiated macrophage cell line THP-1, and resistance to <em>Dictyostelium discoideum</em> predation by NMEC15. We show that ImpK and IcmF are involved in NMEC 15's adherence to HBMEC, and Hcp, ImpK, and IcmF are involved in invasion. The amoeba <em>D. discoideum</em> was used to demonstrate functionality of the T6SS with greater numbers of amoeba required to kill the WT NMEC15 compared to the <em>hcp</em> deletion mutant.</div><div>These studies provide further evidence of the potential role of T6SS in NMEC pathogenesis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108282"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928033","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}

引用次数: 0

Differential regulation of key virulence factors by SbfR in Vibrio parahaemolyticus SbfR对副溶血性弧菌关键毒力因子的差异调控

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-03-01 Epub Date: 2026-01-07 DOI: 10.1016/j.micpath.2026.108278

Bin Ni , Yining Zhou , Nan Zhang , Wanpeng Li , Zhukang Tian , Xi Luo , Yiquan Zhang , Renfei Lu

The virulence of Vibrio parahaemolyticus, a seafood-borne pathogen, is mediated by an array of factors, including type III and type VI secretion systems (T3SS and T6SS) and thermostable direct hemolysin (TDH). The GntR-family transcriptional regulator SbfR (VP1649) has recently been identified as a repressor of biofilm formation and an activator of motility. However, its role in regulating the pathogen's virulence remains unexplored. This study demonstrates that SbfR is a pivotal regulator of key virulence phenotypes in V. parahaemolyticus. Deletion of sbfR significantly attenuated lethality in a zebrafish infection model. The mutant exhibited enhanced adhesion to HeLa cells but caused significantly less cytotoxicity. Hemolytic activity, as determined by the Kanagawa phenomenon (KP) test, was unaffected. At the molecular level, SbfR acted as a transcriptional repressor of genes associated with T6SS2 (hcp2, VPA1043, VPA1044) and the Vp-PAI master regulator vtrA, while it activated the expression of T3SS1-related genes (exsA, VP1667, VP1687). Two-plasmid lacZ reporter assays in a heterologous E. coli system confirmed that SbfR may directly modulate the promoter activities of these T6SS2 and T3SS1 genes. Our findings establish SbfR as a transcriptional regulator that represses adhesion mediated by T6SS2, promotes T3SS1-dependent cytotoxicity, and is essential for full pathogenicity in vivo.

副溶血性弧菌是一种海产病原体，其毒力由一系列因素介导，包括III型和VI型分泌系统（T3SS和T6SS）和耐热性直接溶血素（TDH）。gntr家族转录调节因子SbfR （VP1649）最近被确定为生物膜形成的抑制因子和运动的激活因子。然而，它在调节病原体毒力方面的作用仍未被探索。本研究表明，SbfR是副溶血性弧菌关键毒力表型的关键调节因子。在斑马鱼感染模型中，sbfR的缺失显著降低了致死率。突变体对HeLa细胞的粘附增强，但细胞毒性明显减弱。神奈川现象（KP）试验测定的溶血活性未受影响。在分子水平上，SbfR作为T6SS2相关基因（hcp2、VPA1043、VPA1044）和Vp-PAI主调控因子vtrA的转录抑制因子，同时激活t3ss1相关基因（exsA、VP1667、VP1687）的表达。在异源大肠杆菌系统中进行的双质粒lacZ报告子实验证实，SbfR可能直接调节T6SS2和T3SS1基因的启动子活性。我们的研究结果表明，SbfR是一种转录调节因子，可抑制T6SS2介导的粘附，促进t3ss1依赖性细胞毒性，并对体内完全致病性至关重要。

{"title":"Differential regulation of key virulence factors by SbfR in Vibrio parahaemolyticus","authors":"Bin Ni , Yining Zhou , Nan Zhang , Wanpeng Li , Zhukang Tian , Xi Luo , Yiquan Zhang , Renfei Lu","doi":"10.1016/j.micpath.2026.108278","DOIUrl":"10.1016/j.micpath.2026.108278","url":null,"abstract":"<div><div>The virulence of <em>Vibrio parahaemolyticus</em>, a seafood-borne pathogen, is mediated by an array of factors, including type III and type VI secretion systems (T3SS and T6SS) and thermostable direct hemolysin (TDH). The GntR-family transcriptional regulator SbfR (VP1649) has recently been identified as a repressor of biofilm formation and an activator of motility. However, its role in regulating the pathogen's virulence remains unexplored. This study demonstrates that SbfR is a pivotal regulator of key virulence phenotypes in <em>V. parahaemolyticus</em>. Deletion of <em>sbfR</em> significantly attenuated lethality in a zebrafish infection model. The mutant exhibited enhanced adhesion to HeLa cells but caused significantly less cytotoxicity. Hemolytic activity, as determined by the Kanagawa phenomenon (KP) test, was unaffected. At the molecular level, SbfR acted as a transcriptional repressor of genes associated with T6SS2 (<em>hcp2</em>, VPA1043, VPA1044) and the Vp-PAI master regulator <em>vtrA</em>, while it activated the expression of T3SS1-related genes (<em>exsA</em>, VP1667, VP1687). Two-plasmid <em>lacZ</em> reporter assays in a heterologous <em>E. coli</em> system confirmed that SbfR may directly modulate the promoter activities of these T6SS2 and T3SS1 genes. Our findings establish SbfR as a transcriptional regulator that represses adhesion mediated by T6SS2, promotes T3SS1-dependent cytotoxicity, and is essential for full pathogenicity <em>in vivo</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"212 ","pages":"Article 108278"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928142","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}

引用次数: 0