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Structure and composition of early biofilms formed on dental implants are complex, diverse, subject-specific and dynamic. 牙种植体上形成的早期生物膜结构和组成复杂多样,具有主体特异性和动态性。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-24 DOI: 10.1038/s41522-024-00624-3
Sophie Dieckow, Szymon P Szafrański, Jasmin Grischke, Taoran Qu, Katharina Doll-Nikutta, Matthias Steglich, Ines Yang, Susanne Häussler, Meike Stiesch

Biofilm-associated peri-implant infections pose a major problem in modern medicine. The understanding of biofilm development is hampered by biofilm complexity and the lack of robust clinical models. This study comprehensively characterized the dynamics of early biofilm formation in the transmucosal passage of implant abutments in 12 patients. Biofilm structures and compositions were complex, diverse, subject-specific and dynamic. A total of 371 different bacterial species were detected. 100 phylogenetically diverse unnamed species and 35 taxonomically diverse disease-associated species comprised an average 4.3% and 3.1% of the community, respectively, but reached up to 12.7% and 21.7% in some samples. Oral taxa formed numerous positive associations and clusters and were characterized by a high potential for metabolic interactions. The subspecies diversity was highly patient-specific and species-dependent, with 1427 ASVs identified in total. The unprecedented depth of early biofilm characterization in this study will support the development of individualized preventive and early diagnostic strategies.

生物膜相关的种植体周围感染是现代医学的主要问题。生物膜的复杂性和缺乏健全的临床模型阻碍了对生物膜发育的理解。本研究全面描述了12例患者种植基牙粘膜通道早期生物膜形成的动态。生物膜结构和组成复杂多样,具有主体特异性和动态性。共检出371种不同的细菌。100种系统发育多样的未命名种和35种分类上多样的疾病相关种分别占群落的平均4.3%和3.1%,但在某些样本中高达12.7%和21.7%。口腔类群形成了许多正相关和集群,并以代谢相互作用的高潜力为特征。亚种多样性具有高度的患者特异性和物种依赖性,共鉴定出1427种asv。在这项研究中,早期生物膜特征的空前深度将支持个性化预防和早期诊断策略的发展。
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引用次数: 0
Roles of gut microbiome-associated metabolites in pulmonary fibrosis by integrated analysis. 综合分析肠道微生物相关代谢物在肺纤维化中的作用
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-19 DOI: 10.1038/s41522-024-00631-4
Jie Li, Wenqing Wu, Xinyi Kong, Xia Yang, Kui Li, Zicheng Jiang, Chunlan Zhang, Jun Zou, Ying Liang

Lung diseases often coincide with imbalances in gut microbiota, but the role of gut microbiota in pulmonary fibrosis (PF) remains unclear. This study investigates the impact of gut microbiota and their metabolites on PF. Serum and lung tissues of normal, bleomycin (BLM)- and silica-induced mice showed significant differences in gut microbiota. L-Tryptophan was upregulated within pulmonary tissue and serum metabolites both in the BLM and Silica groups. The dominant gut microbiota associated with L-tryptophan metabolism included Lachnospiraceae_NK4A136_Group, Allobaculum, Alistipes, and Candidatus_Saccharimonas. L-Tryptophan promoted BLM- and silica-induced pathological damage in PF mice. L-Tryptophan promoted TGF-β1-induced EMT and fibroblast activation in vitro via activating the mTOR/S6 pathway. In conclusion, PF mice exhibited alterations in gut microbiota and serum and lung tissue metabolites. L-Tryptophan level was associated with changes in gut microbiota, and L-tryptophan promoted PF progression in both in vivo and in vitro models, potentially through activation of the mTOR/S6 pathway.

肺部疾病通常与肠道菌群失衡相吻合,但肠道菌群在肺纤维化(PF)中的作用尚不清楚。本研究探讨了肠道菌群及其代谢物对PF的影响。正常小鼠、博来霉素(BLM)诱导小鼠和二氧化硅诱导小鼠的血清和肺组织中肠道菌群存在显著差异。BLM组和Silica组肺组织和血清代谢产物中l -色氨酸水平上调。与l -色氨酸代谢相关的主要肠道微生物群包括Lachnospiraceae_NK4A136_Group、Allobaculum、Alistipes和Candidatus_Saccharimonas。l -色氨酸促进BLM和二氧化硅诱导的PF小鼠病理损伤。l -色氨酸通过激活mTOR/S6通路促进TGF-β1诱导的EMT和成纤维细胞的体外活化。总之,PF小鼠的肠道菌群、血清和肺组织代谢产物发生了改变。l -色氨酸水平与肠道微生物群的变化有关,在体内和体外模型中,l -色氨酸可能通过激活mTOR/S6途径促进PF的进展。
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引用次数: 0
Revealing an unprecedented diversity of episymbiotic Saccharibacteria in a high-quality genome collection. 在高质量的基因组收集中揭示了前所未有的表观共生糖菌多样性。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-19 DOI: 10.1038/s41522-024-00617-2
Wenxin He, Hewei Liang, Wenxi Li, Xiaowei Gao, Tongyuan Hu, Xiaoqian Lin, Zhinan Wu, Jingxi Sun, Xiaofang Li, Mengmeng Wang, Xiaoxue Hou, Zhuye Jie, Xin Tong, Xin Jin, Liang Xiao, Yuanqiang Zou

The episymbiotic Candidatus Saccharibacteria is the most studied lineage of candidate phyla radiation. Living an epiparasitic lifestyle, Saccharibacteria might be associated with human mucosal diseases by modulating the structure of the oral microbiome through interactions with host bacteria. However, the knowledge of Saccharibacterial genomic diversity and the potential underlying their adaptation to a wide range of habitats remains limited. Here, we construct a high-quality genome collection of Saccharibacteria from multiple sources, providing 2041 high-quality genomes and previously unidentified taxa. The comparative genomic analysis shows the widespread metabolic defects of Saccharibacteria. Specific metabolic modules are commonly found in Saccharibacteria of different habitats, suggesting Saccharibacteria might have undergone habitat adaptation during the transition from different environments. We additionally show that Saccharibacteria account for ~1% of the Chinese oral microbiome. A preliminary analysis of rheumatoid arthritis individuals and healthy controls implies that Saccharibacteria might be associated with human systemic disease.

附生的Candidatus Saccharibacteria是研究最多的候选辐射门谱系。作为一种外寄生的生活方式,糖菌可能通过与宿主细菌的相互作用来调节口腔微生物群的结构,从而与人类粘膜疾病有关。然而,对糖菌基因组多样性及其适应广泛生境的潜力的了解仍然有限。在此,我们从多个来源构建了一个高质量的糖菌基因组集合,提供了2041个高质量的基因组和以前未识别的分类群。比较基因组分析表明,糖菌普遍存在代谢缺陷。特定的代谢模块在不同生境的糖菌中普遍存在,表明糖菌可能在从不同环境过渡的过程中经历了生境适应。我们还表明,糖菌占中国口腔微生物群的约1%。对类风湿关节炎个体和健康对照者的初步分析表明,糖菌可能与人类全身性疾病有关。
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引用次数: 0
Diverse polysaccharide production and biofilm formation abilities of clinical Klebsiella pneumoniae. 临床肺炎克雷伯氏菌的多种多糖生产和生物膜形成能力。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-19 DOI: 10.1038/s41522-024-00629-y
Robert L Beckman, Elenora Cella, Taj Azarian, Olaya Rendueles, Renee M Fleeman

Klebsiella pneumoniae infections have become a growing threat for human health. The lack of understanding of the relationship between antibiotic resistance, mucoviscosity, and biofilm formation impedes our abilities to effectively predict K. pneumoniae infection outcomes. The Multidrug-Resistant Organism Repository and Surveillance Network offers a unique opportunity into the genetic and phenotypic variabilities in the K. pneumoniae isolates. To this end, we compared the genetic profiles of these isolates with the phenotypic biofilm formation, percent mucoviscosity, and growth rates. There was a significant phenotype-genotype correlation with decreased biofilm formation and an insertion sequence in the transcriptional activator of the type III fimbrial system. Interestingly, the most mucoid strains in the populations were lacking the genetic element regulating the mucoid phenotype and three of these isolates were able to form robust biofilms. The combination of phenotypic, genomic, and image analyses revealed an intricate relation between growth, mucoviscosity and specific virulence-associated genetic determinants.

肺炎克雷伯菌感染已成为日益严重的人类健康威胁。缺乏对抗生素耐药性、黏液粘度和生物膜形成之间关系的理解,阻碍了我们有效预测肺炎克雷伯菌感染结果的能力。多药耐药生物库和监测网络为肺炎克雷伯菌分离株的遗传和表型变异提供了独特的机会。为此,我们将这些分离株的遗传谱与表型生物膜形成、黏度百分比和生长速率进行了比较。表型-基因型与生物膜形成减少和III型毛系统转录激活子插入序列存在显著相关性。有趣的是,群体中大多数粘液样菌株缺乏调节粘液样表型的遗传元件,其中三个分离株能够形成坚固的生物膜。表型、基因组和图像分析的结合揭示了生长、黏液粘度和特异性毒力相关遗传决定因素之间的复杂关系。
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引用次数: 0
Machine learning analysis of sex and menopausal differences in the gut microbiome in the HELIUS study. 对 HELIUS 研究中肠道微生物组的性别和更年期差异的机器学习分析。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-19 DOI: 10.1038/s41522-024-00628-z
Esther M C Vriend, Henrike Galenkamp, Hilde Herrema, Max Nieuwdorp, Bert-Jan H van den Born, Barbara J H Verhaar

Sex differences in the gut microbiome have been examined previously, but results are inconsistent, often due to small sample sizes. We investigated sex and menopausal differences in the gut microbiome in a large multi-ethnic population cohort study, including 5166 participants. Using machine learning models, we revealed modest associations between sex and menopausal status, and gut microbiota composition (AUC 0.61-0.63). After adjustments for age, cardiovascular risk factors, and diet, a part of the associations of the highest-ranked gut microbes with sex were attenuated, but most associations remained significant. In contrast, most associations with menopausal status were driven by age and lost significance after adjustment. Using pathway analyses on metagenomic data, we identified sex differences in vitamin B6 synthesis and stachyose degradation pathways. Since some of sex differences in gut microbiome composition and function could not be explained by covariates, we recommend sex stratification in future microbiome studies.

以前已经研究过肠道微生物组的性别差异,但结果不一致,通常是由于样本量小。我们在一项包括5166名参与者的大型多种族人群队列研究中调查了肠道微生物组的性别和绝经期差异。使用机器学习模型,我们揭示了性别与绝经状态和肠道微生物群组成之间的适度关联(AUC为0.61-0.63)。在对年龄、心血管危险因素和饮食进行调整后,排名最高的肠道微生物与性别的部分关联减弱,但大多数关联仍然显著。相反,大多数与绝经状态的关联是由年龄驱动的,在调整后失去了意义。利用宏基因组数据的途径分析,我们确定了维生素B6合成和水苏糖降解途径的性别差异。由于肠道微生物组组成和功能的一些性别差异不能用协变量来解释,我们建议在未来的微生物组研究中进行性别分层。
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引用次数: 0
Root carbon inputs outweigh litter in shaping grassland soil microbiomes and ecosystem multifunctionality. 在塑造草地土壤微生物群和生态系统多功能性方面,根系碳输入超过了枯落物。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-19 DOI: 10.1038/s41522-024-00616-3
Jiayin Feng, Linlin Wang, Changchun Zhai, Lin Jiang, Yunfeng Yang, Xiaowei Huang, Jingyi Ru, Jian Song, Limei Zhang, Shiqiang Wan

Global change has the potential to alter soil carbon (C) inputs from above- and below-ground sources, with subsequent influences on soil microbial communities and ecological functions. Using data from a 13-year field experiment in a semi-arid grassland, we investigated the effects of litter manipulations and plant removal on soil microbiomes and ecosystem multifunctionality (EMF). Litter addition did not affect soil microbial α-diversity whereas litter removal reduced bacterial and fungal α-diversity due to decreased C substrate supply and soil moisture. By contrast, plant removal led to larger declines in bacterial and fungal α-diversity, lower microbial network stability and complexity. EMF was enhanced by litter addition but largely reduced by plant removal, primarily attributed to the loss of fungal diversity. Our findings underscore the importance of C inputs in shaping soil microbiomes and highlight the dominant role of plant root-derived C inputs in maintaining ecological functions under global change scenarios.

全球变化有可能改变地上和地下来源的土壤碳(C)输入,进而对土壤微生物群落和生态功能产生影响。利用13年半干旱草地的田间试验数据,研究了凋落物处理和植物去除对土壤微生物组和生态系统多功能性的影响。凋落物的添加对土壤微生物α-多样性没有影响,而凋落物的去除由于减少了C基质供给和土壤湿度,降低了细菌和真菌α-多样性。相比之下,植物去除导致细菌和真菌α-多样性大幅下降,微生物网络稳定性和复杂性降低。凋落物的增加增加了EMF,但植物的移除大大降低了EMF,这主要归因于真菌多样性的丧失。我们的研究结果强调了碳输入在塑造土壤微生物组中的重要性,并强调了全球变化情景下植物根源碳输入在维持生态功能方面的主导作用。
{"title":"Root carbon inputs outweigh litter in shaping grassland soil microbiomes and ecosystem multifunctionality.","authors":"Jiayin Feng, Linlin Wang, Changchun Zhai, Lin Jiang, Yunfeng Yang, Xiaowei Huang, Jingyi Ru, Jian Song, Limei Zhang, Shiqiang Wan","doi":"10.1038/s41522-024-00616-3","DOIUrl":"10.1038/s41522-024-00616-3","url":null,"abstract":"<p><p>Global change has the potential to alter soil carbon (C) inputs from above- and below-ground sources, with subsequent influences on soil microbial communities and ecological functions. Using data from a 13-year field experiment in a semi-arid grassland, we investigated the effects of litter manipulations and plant removal on soil microbiomes and ecosystem multifunctionality (EMF). Litter addition did not affect soil microbial α-diversity whereas litter removal reduced bacterial and fungal α-diversity due to decreased C substrate supply and soil moisture. By contrast, plant removal led to larger declines in bacterial and fungal α-diversity, lower microbial network stability and complexity. EMF was enhanced by litter addition but largely reduced by plant removal, primarily attributed to the loss of fungal diversity. Our findings underscore the importance of C inputs in shaping soil microbiomes and highlight the dominant role of plant root-derived C inputs in maintaining ecological functions under global change scenarios.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"150"},"PeriodicalIF":7.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Saliva microbiome profiling by full-gene 16S rRNA Oxford Nanopore Technology versus Illumina MiSeq sequencing. 全基因16S rRNA牛津纳米孔技术与Illumina MiSeq测序的唾液微生物组分析。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-18 DOI: 10.1038/s41522-024-00634-1
Anders Esberg, Niklas Fries, Simon Haworth, Ingegerd Johansson
{"title":"Saliva microbiome profiling by full-gene 16S rRNA Oxford Nanopore Technology versus Illumina MiSeq sequencing.","authors":"Anders Esberg, Niklas Fries, Simon Haworth, Ingegerd Johansson","doi":"10.1038/s41522-024-00634-1","DOIUrl":"10.1038/s41522-024-00634-1","url":null,"abstract":"","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"149"},"PeriodicalIF":7.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Probiotics as an adjunctive therapy in periodontitis treatment-reality or illusion-a clinical perspective. 益生菌作为牙周炎治疗的辅助疗法-现实或幻想-临床观点。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-16 DOI: 10.1038/s41522-024-00614-5
Lamyae Baddouri, Matthias Hannig

Periodontitis, a prevalent oral health issue, involves various microorganisms and clinical effects. This review examines probiotics as adjunctive therapy for periodontitis by analyzing forty clinical studies. Findings showed mixed results due to differences in study design, probiotic types, and clinical parameters; however, probiotics improved outcomes in severe cases. Caution is advised when interpreting these results, as longer follow-up periods reveal variability and potential regression in effects.

牙周炎是一个普遍存在的口腔健康问题,涉及各种微生物和临床效果。本综述通过分析 40 项临床研究,探讨了益生菌作为牙周炎辅助疗法的作用。研究结果显示,由于研究设计、益生菌类型和临床参数的差异,结果不一;但是,益生菌改善了严重病例的治疗效果。在解释这些结果时应谨慎,因为较长的随访期会揭示效果的变化和潜在回归。
{"title":"Probiotics as an adjunctive therapy in periodontitis treatment-reality or illusion-a clinical perspective.","authors":"Lamyae Baddouri, Matthias Hannig","doi":"10.1038/s41522-024-00614-5","DOIUrl":"10.1038/s41522-024-00614-5","url":null,"abstract":"<p><p>Periodontitis, a prevalent oral health issue, involves various microorganisms and clinical effects. This review examines probiotics as adjunctive therapy for periodontitis by analyzing forty clinical studies. Findings showed mixed results due to differences in study design, probiotic types, and clinical parameters; however, probiotics improved outcomes in severe cases. Caution is advised when interpreting these results, as longer follow-up periods reveal variability and potential regression in effects.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"148"},"PeriodicalIF":7.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Author Correction: Rumen microbiome and fat deposition in sheep: insights from a bidirectional mendelian randomization study. 作者更正:绵羊瘤胃微生物组与脂肪沉积:双向泯灭随机研究的启示
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-14 DOI: 10.1038/s41522-024-00620-7
Yukun Zhang, Xiaoxue Zhang, Chong Li, Huibin Tian, Xiuxiu Weng, Changchun Lin, Deyin Zhang, Yuan Zhao, Xiaolong Li, Jiangbo Cheng, Liming Zhao, Dan Xu, Xiaobin Yang, Zhihua Jiang, Fadi Li, Weimin Wang
{"title":"Author Correction: Rumen microbiome and fat deposition in sheep: insights from a bidirectional mendelian randomization study.","authors":"Yukun Zhang, Xiaoxue Zhang, Chong Li, Huibin Tian, Xiuxiu Weng, Changchun Lin, Deyin Zhang, Yuan Zhao, Xiaolong Li, Jiangbo Cheng, Liming Zhao, Dan Xu, Xiaobin Yang, Zhihua Jiang, Fadi Li, Weimin Wang","doi":"10.1038/s41522-024-00620-7","DOIUrl":"10.1038/s41522-024-00620-7","url":null,"abstract":"","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"147"},"PeriodicalIF":7.8,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-chain 4-aminoquinolines inhibit filamentation and increase efficacy of nystatin against Candida albicans infections in vivo. 长链 4-氨基喹啉类抑制丝状化并提高奈司他丁对体内白色念珠菌感染的疗效。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-13 DOI: 10.1038/s41522-024-00608-3
Aleksandar Pavic, Natasa Radakovic, Ivana Moric, Nada Stankovic, Dejan Opsenica, Lidija Senerovic

In exploring a growing demand for innovative approaches to tackle emerging and life threatening fungal diseases, we identified long-chain 4-aminoquinoline (4-AQ) derivatives as a new class of anti-virulence agents. For the first time, we demonstrated that 4-AQs effectively prevent filamentation of Candida albicans, a key virulence trait, under multiple triggering conditions. Selected 4-AQ derivatives inhibited filament formation in a zebrafish model of disseminated candidiasis at 1.56 µM, with no toxicity up to 50 µM. Combining nystatin with 4-AQs resulted in a 100% survival rate of infected embryos and complete eradication of C. albicans, compared to 65-75% survival with nystatin alone. The most potent 4-AQ derivatives also showed significant activity against C. albicans biofilms, with derivative 11 suppressing mixed C. albicans-Pseudomonas aeruginosa biofilms. This dual capability highlights the potential of 4-AQs as novel anti-virulence agents to enhance conventional antifungal therapies, marking a significant advance in treating complex fungal infections.

在探索解决新出现的威胁生命的真菌疾病的创新方法的过程中,我们发现长链 4-氨基喹啉(4-AQ)衍生物是一类新的抗病毒剂。我们首次证明,在多种触发条件下,4-AQ 能有效阻止白色念珠菌的丝状化,而丝状化是一种关键的致病性特征。在斑马鱼播散性念珠菌病模型中,选定的 4-AQ 衍生物在 1.56 µM 的浓度下可抑制菌丝的形成,在 50 µM 的浓度下无毒性。将硝司他丁与 4-AQs 结合使用可使受感染的胚胎存活率达到 100%,并完全根除白念珠菌,而单独使用硝司他丁的存活率仅为 65-75%。最有效的 4-AQ 衍生物对白僵菌生物膜也显示出显著的活性,其中衍生物 11 可抑制白僵菌-铜绿假单胞菌混合生物膜。这种双重能力凸显了 4-AQ 作为新型抗真菌剂增强传统抗真菌疗法的潜力,标志着在治疗复杂真菌感染方面取得了重大进展。
{"title":"Long-chain 4-aminoquinolines inhibit filamentation and increase efficacy of nystatin against Candida albicans infections in vivo.","authors":"Aleksandar Pavic, Natasa Radakovic, Ivana Moric, Nada Stankovic, Dejan Opsenica, Lidija Senerovic","doi":"10.1038/s41522-024-00608-3","DOIUrl":"10.1038/s41522-024-00608-3","url":null,"abstract":"<p><p>In exploring a growing demand for innovative approaches to tackle emerging and life threatening fungal diseases, we identified long-chain 4-aminoquinoline (4-AQ) derivatives as a new class of anti-virulence agents. For the first time, we demonstrated that 4-AQs effectively prevent filamentation of Candida albicans, a key virulence trait, under multiple triggering conditions. Selected 4-AQ derivatives inhibited filament formation in a zebrafish model of disseminated candidiasis at 1.56 µM, with no toxicity up to 50 µM. Combining nystatin with 4-AQs resulted in a 100% survival rate of infected embryos and complete eradication of C. albicans, compared to 65-75% survival with nystatin alone. The most potent 4-AQ derivatives also showed significant activity against C. albicans biofilms, with derivative 11 suppressing mixed C. albicans-Pseudomonas aeruginosa biofilms. This dual capability highlights the potential of 4-AQs as novel anti-virulence agents to enhance conventional antifungal therapies, marking a significant advance in treating complex fungal infections.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"146"},"PeriodicalIF":7.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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npj Biofilms and Microbiomes
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