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Real-time, high-resolution metabolic characterization of live bacteria using label-free optical metabolic imaging. 使用无标签光学代谢成像实时,高分辨率的活细菌代谢特性。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-27 DOI: 10.1038/s41522-026-00920-0
Janet E Sorrells, Lingxiao Yang, Rishyashring R Iyer, Farzana R Zaki, Adam A Markowicz, Guillermo L Monroy, Edita Aksamitiene, Marina Marjanovic, Stephen A Boppart

Label-free optical imaging provides non-invasive, high-speed, high-resolution metabolic characterization of live bacteria with single-cell resolution. Here, we demonstrate the ability of label-free multiphoton autofluorescence microscopy to characterize the fast (between 0 and 30 min) metabolic changes in bacteria in response to antibiotic treatments and observe the cell-to-cell metabolic heterogeneity of planktonic bacteria and biofilms. Results indicate that bacteria exhibit a distinct measurable response to bactericidal treatments within seconds. Furthermore, S. aureus biofilms exhibit metabolic heterogeneity, with local pockets of high metabolic activity. Bacteria in biofilms exhibit altered metabolic profiles compared to planktonic bacteria for all four species examined: S. aureus, P. aeruginosa, M. catarrhalis, and S. pneumoniae. These results shed light on the spatial and temporal metabolic heterogeneity of bacteria and the quantification possibilities using label-free nonlinear optical microscopy.

无标签光学成像提供无创、高速、高分辨率的单细胞活细菌代谢特征。在这里,我们证明了无标记的多光子自体荧光显微镜能够表征细菌对抗生素治疗的快速代谢变化(在0到30分钟之间),并观察浮游细菌和生物膜的细胞间代谢异质性。结果表明,细菌在几秒钟内对杀菌处理表现出明显的可测量的反应。此外,金黄色葡萄球菌生物膜表现出代谢异质性,局部具有高代谢活性。与浮游细菌相比,生物膜中的细菌在所有四种被检查的物种中表现出改变的代谢谱:金黄色葡萄球菌、铜绿假单胞菌、卡他利分枝杆菌和肺炎链球菌。这些结果揭示了细菌的时空代谢异质性以及使用无标记非线性光学显微镜进行量化的可能性。
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引用次数: 0
Modulation of gut microbiota and its metabolite Equol by Huaier granule suppresses hepatocellular carcinoma via the gut-liver axis. 怀尔颗粒调节肠道菌群及其代谢物马酚通过肠-肝轴抑制肝癌。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-26 DOI: 10.1038/s41522-026-00919-7
Xuejiao Wei, Huiming Huang, Fei Wang, Peng Tan, Zhuguo Wang, Xinyu Qiu, Ruoxin Zhang, Yufeng Gao, Pengfei Tu, Zhongdong Hu

Hepatocellular carcinoma (HCC) is a frequently seen malignant tumor globally. Huaier is the dried fruiting body of the fungus Trametes robiniophila Murr. Huaier granule (HEG), formulated from the Huaier extract, is a Class I innovative anti-cancer drug in China and exhibits significant anti-HCC effects in clinical settings. Nevertheless, the specific mechanisms underlying its efficacy remain incompletely understood. This research demonstrated that HEG effectively suppressed tumor development in the orthotopic HCC mouse model in a gut microbiota-dependent manner and modified the gut microbiota composition. Notably, the primary differential bacterial genera between the Model group and the HEG group included Adlercreutzia. HEG exerted anti-HCC effects by repairing the intestinal barrier, improving colon immunity, and ameliorating the immune microenvironment by suppressing the MAPK signaling pathway via the gut microbiota-gut-liver axis. By integrating 16S rRNA sequencing with metabolomics data, supplemented by literature mining and in vitro validation, Equol, produced by specific gut microbiota Adlercreutzia, was identified as a key metabolite through which HEG exerted its anti-HCC effects by modulating gut microbiota. Moreover, Equol was essential for the anti-HCC effects of HEG. Additionally, Equol ameliorated the immune microenvironment through inhibiting the MAPK signaling pathway, while concurrently inhibiting the growth of HCC cells by inducing the G0/G1 phase blockade through suppression of Cyclin E1-CDK2/Rb signaling pathway. This study provided a robust scientific foundation for the clinical use of HEG, with Equol emerging as a promising candidate for HCC treatment.

肝细胞癌(HCC)是全球常见的恶性肿瘤。槐儿是真菌赤霉素(Trametes robiniophila Murr)的干子实体。怀尔颗粒(HEG)是由怀尔提取物配制而成的中国一类创新抗癌药物,在临床中具有显著的抗hcc作用。然而,其功效背后的具体机制仍不完全清楚。本研究表明,HEG以肠道菌群依赖的方式有效抑制原位肝癌小鼠模型的肿瘤发展,并改变肠道菌群组成。值得注意的是,模型组和HEG组之间的主要差异细菌属包括克氏Adlercreutzia。HEG通过抑制MAPK信号通路,通过肠道微生物-肠-肝轴,修复肠道屏障,提高结肠免疫力,改善免疫微环境,发挥抗hcc作用。通过将16S rRNA测序与代谢组学数据整合,并辅以文献挖掘和体外验证,确定了特异性肠道菌群阿德勒克氏菌产生的马酚是HEG通过调节肠道菌群发挥抗hcc作用的关键代谢物。此外,马雌酚对HEG的抗hcc作用至关重要。此外,马雌酚通过抑制MAPK信号通路改善免疫微环境,同时通过抑制Cyclin E1-CDK2/Rb信号通路诱导G0/G1期阻断,抑制HCC细胞的生长。该研究为HEG的临床应用提供了坚实的科学基础,雌马酚有望成为HCC治疗的候选药物。
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引用次数: 0
Dietary fiber deficiency exacerbates intestinal inflammation via miR-6240-enriched gut extracellular vesicles. 膳食纤维缺乏通过富含mir -6240的肠道细胞外囊泡加剧肠道炎症。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-24 DOI: 10.1038/s41522-026-00918-8
Mengzhen Song, Wenjun Zhou, Jinping Fan, Demin Cai, Hong Wei, Shiyu Tao

Emerging evidence underscores the critical role of dietary fiber in maintaining gut homeostasis. While extracellular vesicles (EVs) have recently gained attention as key mediators of host-microbe communication, their functional contribution to fiber deficiency-associated pathologies remains largely unexplored. In this study, we revealed that a fiber-free diet induces significant intestinal inflammatory damage in mice, an effect that can be faithfully reproduced through fecal microbiota transplantation. Importantly, we demonstrated that intestinal epithelial cells-derived EVs from fiber-deprived mice are sufficient to recapitulate the detrimental effects of fiber deficiency. Mechanistic studies revealed enrichment of miR-6240 in these EVs, which targeted the 3'UTR of STAT6 mRNA to suppress its expression. This impairment of STAT6 signaling inhibited M2 macrophage polarization, exacerbating intestinal inflammation. This novel pathway is further validated in primary macrophage adoptive transfer experiments. Our work unveils a previously unrecognized mechanism by which fiber deficiency exacerbates intestinal inflammation through IECs-derived EVs and miR-6240/STAT6-mediated macrophage dysfunction.

新出现的证据强调了膳食纤维在维持肠道内稳态中的关键作用。虽然细胞外囊泡(EVs)作为宿主-微生物通讯的关键介质最近受到关注,但它们在纤维缺乏相关病理中的功能贡献仍未得到充分研究。在这项研究中,我们发现无纤维饮食会引起小鼠肠道炎症损伤,这种效果可以通过粪便微生物群移植忠实地复制。重要的是,我们证明了来自纤维剥夺小鼠的肠上皮细胞来源的ev足以概括纤维缺乏的有害影响。机制研究显示miR-6240在这些ev中富集,其靶向STAT6 mRNA的3'UTR抑制其表达。这种STAT6信号的损伤抑制了M2巨噬细胞的极化,加剧了肠道炎症。该新途径在原代巨噬细胞过继性转移实验中得到进一步验证。我们的工作揭示了一种以前未被认识到的机制,即纤维缺乏通过iec衍生的ev和miR-6240/ stat6介导的巨噬细胞功能障碍加剧肠道炎症。
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引用次数: 0
Gut microbiome-driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming. 通过免疫、代谢、神经和内分泌轴重编程的肠道微生物驱动的结直肠癌。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-23 DOI: 10.1038/s41522-025-00883-8
Jhommara Bautista, Mónica Lamas-Maceiras, Camila Hidalgo-Tinoco, Antonio Guerra-Guerrero, Anapaula Betancourt-Velarde, Andrés López-Cortés

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide and is increasingly recognized as the outcome of complex host-microbe interactions. Beyond established genetic and environmental drivers, the gut microbiome has emerged as a causal and mechanistic contributor to CRC initiation, progression, and therapy response. This review synthesizes current molecular, ecological, and translational evidence to explain how gut microbial communities reprogram immune, metabolic, neural, and endocrine networks within the tumor microenvironment. CRC-associated dysbiosis is characterized by enrichment of pathobionts such as Fusobacterium nucleatum, pks⁺ Escherichia coli, and enterotoxigenic Bacteroides fragilis, and by loss of protective, short-chain-fatty-acid-producing commensals. These microbes promote carcinogenesis through genotoxin-induced DNA damage, epithelial barrier disruption, metabolic rewiring, and chronic inflammation that collectively sustain immune suppression and tumor growth. Defined mutational signatures from bacterial metabolites, including colibactin, cytolethal distending toxin, and indolimines, now directly link microbial exposures to human cancer genomes. By integrating these findings, this review conceptualizes CRC as a biofilm-structured, microbiome-driven ecosystem disease, where polymicrobial consortia coordinate barrier breakdown, immune evasion, and metabolic cooperation. Finally, we highlight emerging microbiota-targeted strategies, including dietary modulation, pre- and probiotics, postbiotics, bacteriophage therapy, engineered live biotherapeutics, and fecal microbiota transplantation, that translate these insights into precision prevention and therapy. Through this integrative framework, the review aims to reposition the microbiome from a correlative feature to a tractable determinant of CRC pathogenesis and treatment response.

结直肠癌(CRC)是世界范围内癌症死亡的主要原因,并且越来越多地被认为是复杂的宿主-微生物相互作用的结果。除了已建立的遗传和环境驱动因素外,肠道微生物组已成为结直肠癌发生、进展和治疗反应的因果和机制因素。这篇综述综合了目前的分子、生态和转化证据来解释肠道微生物群落如何在肿瘤微环境中重新编程免疫、代谢、神经和内分泌网络。crc相关的生态失调的特征是病原体如核梭杆菌、pks +大肠杆菌和产肠毒素的脆弱拟杆菌的富集,以及保护性短链脂肪酸产生共生菌的丧失。这些微生物通过基因毒素诱导的DNA损伤、上皮屏障破坏、代谢重新布线和慢性炎症促进致癌,共同维持免疫抑制和肿瘤生长。从细菌代谢物(包括大肠杆菌蛋白、细胞致死膨胀毒素和吲哚胺)中确定的突变特征,现在直接将微生物暴露与人类癌症基因组联系起来。通过整合这些发现,本综述将CRC定义为一种生物膜结构,微生物组驱动的生态系统疾病,其中多微生物联盟协调屏障破坏,免疫逃避和代谢合作。最后,我们强调了新兴的针对微生物群的策略,包括饮食调节,益生菌前和益生菌,后益生菌,噬菌体治疗,工程活生物治疗和粪便微生物群移植,将这些见解转化为精确的预防和治疗。通过这一综合框架,该综述旨在将微生物组从CRC发病机制和治疗反应的相关特征重新定位为可处理的决定因素。
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引用次数: 0
Biofilms: from the cradle of life to life support. 生物膜:从生命的摇篮到生命的维持。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-22 DOI: 10.1038/s41522-025-00875-8
Katherine J Baxter, Eszter Sas, Kevin B Clark, Michaela Walsh, Nikhil Pradeep, Alavia Batool, Charles Naney, Miguel Angel Vargas Cruz, Niamh Kennerdale, Kajari Das, Zhihan Shi, Anish Kelam, Vandana Verma, Marta Filipa Simões, Dirk Neefs, Vinothkannan Ravichandran, Madhan R Tirumalai, Borja Barbero Barcenilla, Guerrino Macori, Emmanuel Gonzalez, Benjamin Sikes, Fathi Karouia, Nicholas J B Brereton

Biofilms are intricately associated with life on Earth, enabling functions essential to human and plant systems, but their susceptibility to spaceflight stressors and functional disruption in space remains incompletely understood. During spaceflight, biofilms have largely been considered as potential infrastructure, life support or infection risks. This review focuses on the prevailing beneficial roles of biofilms in human and plant health, and examines evidence of biofilm adaptability in space environments.

生物膜与地球上的生命有着错综复杂的联系,为人类和植物系统提供了必要的功能,但它们对太空飞行压力源和太空功能破坏的敏感性仍未完全了解。在太空飞行中,生物膜在很大程度上被认为是潜在的基础设施、生命支持或感染风险。本文综述了生物膜在人类和植物健康中普遍存在的有益作用,并研究了生物膜在空间环境中的适应性证据。
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引用次数: 0
Profound taxonomic and functional gut microbiota alterations associated with trichuriasis: cross-country and country-specific patterns. 与鞭虫病相关的深刻的分类学和功能性肠道微生物群改变:跨国和国别特有模式。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-21 DOI: 10.1038/s41522-026-00911-1
Pierre H H Schneeberger, Julian Dommann, Nurudeen Rahman, Eveline Hürlimann, Somphou Sayasone, Said Ali, Jean Tenena Coulibaly, Jennifer Keiser

The human gut microbiota is vital for immune function, metabolism, and resistance to pathogens. Soil-transmitted helminths like Trichuris trichiura can disrupt this microbial community, but the extent and functional significance of these disruptions across diverse regions remain unclear. We investigated the impact of T. trichiura infection on gut microbiota composition and function in three endemic regions-Côte d'Ivoire, Laos, and Tanzania-using standardized, high-resolution metagenomic profiling. Our findings reveal consistent depletion of key short-chain fatty acid (SCFA) producers, including Blautia sp. MSJ 9 and Holdemanella biformis, and enrichment of mucin-degrading genera such as Ruminococcus and Bacteroides. These changes coincided with increased microbial utilization of host-derived carbohydrates and destabilization of microbial networks, notably with the emergence of Segatella copri in infected individuals. Although taxa-level responses varied by region, similar trends in SCFA depletion and mucin degradation were observed across sites, pointing to a potentially shared metabolic response to infection. These alterations suggest compromised gut barrier function and immune modulation, potentially promoting parasite persistence. Our results underscore the potential of microbiome-based strategies, such as targeted probiotics or dietary interventions, to support helminth control by restoring microbial balance and improving host resilience.

人体肠道菌群对免疫功能、新陈代谢和抵抗病原体至关重要。像Trichuris trichiura这样的土壤传播蠕虫可以破坏这种微生物群落,但这些破坏在不同地区的程度和功能意义尚不清楚。我们使用标准化、高分辨率宏基因组分析方法,研究了毛螺旋体感染对regions-Côte科特迪瓦、老挝和坦桑尼亚三个流行国家肠道微生物群组成和功能的影响。我们的研究结果表明,关键短链脂肪酸(SCFA)生产者,包括Blautia sp. msj9和biformholdemanella,持续减少,而粘液降解属,如Ruminococcus和Bacteroides的富集。这些变化与微生物对宿主来源的碳水化合物的利用增加和微生物网络的不稳定相吻合,特别是与感染个体中出现的copri segella相吻合。尽管不同地区的分类群水平反应不同,但在不同地点观察到相似的SCFA消耗和粘蛋白降解趋势,这表明对感染的潜在共同代谢反应。这些改变表明肠道屏障功能和免疫调节受损,可能促进寄生虫的持续存在。我们的研究结果强调了基于微生物组的策略的潜力,例如靶向益生菌或饮食干预,通过恢复微生物平衡和提高宿主恢复力来支持蠕虫控制。
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引用次数: 0
Probiotic bacteria Bifidobacterium bifidum upregulation of intestinal epithelial tight junction barrier is mediated by TLR-2/TLR-6 receptor complex activation of occludin gene. 益生菌两歧双歧杆菌上调肠上皮紧密连接屏障是通过TLR-2/TLR-6受体复合物激活occludin基因介导的。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-21 DOI: 10.1038/s41522-025-00903-7
Raz Abdulqadir, Rana Al-Sadi, Yash Gupta, Manmeet Rawat, Thomas Ma

Defective intestinal epithelial tight junction (TJ) barrier is a key pathogenic factor of inflammatory bowel disease (IBD). Probiotic bacterial upregulation of intestinal TJ barrier has been shown to prevent the development of intestinal inflammation. However, the mechanism of microbe-host interactions responsible for the TJ barrier upregulation remains unclear. This study investigates the molecular mechanisms by which a particular strain of probiotic bacteria, Bifidobacterium bifidum (BB1), upregulates the intestinal epithelial TJ barrier. Using in vitro (filter-grown Caco-2 monolayers) and in vivo (recycling intestinal perfusion in live mice) intestinal epithelial model system, we show that BB1 upregulation of intestinal TJ barrier correlated with an increase in occludin gene activity (occludin promoter activity and occludin mRNA transcription levels) and protein expression, with no changes in other TJ proteins. Occludin knockdown or inhibition of gene transcription prevented the enhancement of the TJ barrier, confirming the essential role of BB1-induced occludin gene activation in TJ barrier enhancement, which was mediated sequentially by BB1 activation of the intestinal epithelial cell TLR-2/TLR-6 complex and IRAK-1 phosphorylation, as well as the apical membrane recruitment of the adapter protein TOLLIP. These findings provide novel mechanistic insight into the microbe-host interactions driving probiotic bacteria upregulation of intestinal TJ barrier.

肠上皮紧密连接屏障缺陷是炎症性肠病(IBD)的关键致病因素。益生菌上调肠道TJ屏障已被证明可以预防肠道炎症的发生。然而,微生物-宿主相互作用导致TJ屏障上调的机制尚不清楚。本研究探讨了一种特殊的益生菌——两歧双歧杆菌(Bifidobacterium bifidum, BB1)上调肠上皮TJ屏障的分子机制。通过体外(过滤培养caco2单层)和体内(活小鼠肠道循环灌注)肠上皮模型系统,我们发现肠道TJ屏障BB1上调与occludin基因活性(occludin启动子活性和occludin mRNA转录水平)和蛋白表达增加相关,而其他TJ蛋白没有变化。Occludin敲低或基因转录抑制阻止了TJ屏障的增强,证实了BB1诱导的Occludin基因激活在TJ屏障增强中的重要作用,这一过程依次通过BB1激活肠上皮细胞TLR-2/TLR-6复合体和IRAK-1磷酸化介导,以及接合蛋白TOLLIP的顶膜募集介导。这些发现为微生物-宿主相互作用驱动益生菌上调肠道TJ屏障提供了新的机制见解。
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引用次数: 0
Restoration of ethanol-induced Bifidobacterium pseudocatenulatum depletion ameliorates alcohol-associated liver disease. 恢复乙醇诱导的假芽双歧杆菌枯竭改善酒精相关的肝脏疾病。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-20 DOI: 10.1038/s41522-026-00913-z
Yating Li, Liya Yang, Hong Xu, Xiaoyuan Bian, Ding Shi, Wenrui Wu, Lanjuan Li

Alcohol-associated liver disease (ALD), characterized by gut barrier disruption and microbial dysbiosis, is associated with significant depletion of the genus Bifidobacterium in patients, as evidenced by our cohort of 127 subjects. Functional screening revealed B. pseudocatenulatum as a protective strain. In a murine ALD model established with a Lieber-DeCarli ethanol diet, oral administration of B. pseudocatenulatum for 8 weeks ameliorated hepatomegaly, steatosis, and serum transaminase levels. Probiotic intervention restored intestinal barrier function, as indicated by reduced lipopolysaccharide-binding proteins and upregulated tight junction protein expression. Microbiome analysis revealed a mitigation of dysbiosis, with a reduction in pathogenic Escherichia-Shigella and Parabacteroides and an enrichment of beneficial Bifidobacterium and Blautia, concomitant with shifts in lipid metabolism. Mechanistically, B. pseudocatenulatum-derived short-chain fatty acids downregulated the expression of hepatic lipogenic genes (Cd36, Fasn, Accα) and pro-inflammatory cytokines (Il-1β, Ccl2, Tnf-α). These results suggest that B. pseudocatenulatum is a promising probiotic candidate for ALD management.

以肠道屏障破坏和微生物生态失调为特征的酒精相关性肝病(ALD)与患者双歧杆菌属的显著耗竭有关,127名受试者的队列研究证实了这一点。功能筛选结果显示,伪芽孢杆菌为保护菌株。在用Lieber-DeCarli乙醇饮食建立的小鼠ALD模型中,口服假芽孢杆菌8周可改善肝肿大、脂肪变性和血清转氨酶水平。通过降低脂多糖结合蛋白和上调紧密连接蛋白的表达,益生菌干预恢复了肠道屏障功能。微生物组分析显示,随着致病性志贺氏杆菌和副芽孢杆菌的减少,有益双歧杆菌和蓝杆菌的丰富,伴随着脂质代谢的变化,生态失调得到缓解。从机制上讲,假芽孢杆菌衍生的短链脂肪酸下调了肝脏脂肪生成基因(Cd36、Fasn、Accα)和促炎细胞因子(Il-1β、Ccl2、Tnf-α)的表达。这些结果表明假芽孢杆菌是一种很有前途的治疗ALD的候选益生菌。
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引用次数: 0
Intermittent antibiotic exposure of Escherichia coli biofilms drives resistance in catheter-associated infection models. 在导管相关感染模型中,间歇性抗生素暴露于大肠杆菌生物膜驱动耐药性。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-17 DOI: 10.1038/s41522-025-00906-4
Yutaka Yoshii, Stanislas Thiriet-Rupert, David Lebeaux, Jean-Marc Ghigo, Christophe Beloin

The use of antibiotic lock therapy (ALT) to protect catheters from infection is still being debated due to its inconsistent effectiveness and the potential risk of promoting antibiotic resistance. Using an in vitro infection model of a pediatric venous access port, we demonstrated that 10 days of continuous therapy eradicates Escherichia coli biofilms in vitro without the emergence of antibiotic resistance. By contrast, an 8-h intermittent therapy used for infected parenteral nutrition patients rapidly selected low-level amikacin-resistant mutants both in vitro and in vivo in a clinically relevant rat model, primarily due to convergent fusA, sbmA, and cpxA mutations. Our findings indicate that intermittent dosing generates pulsed selective pressure, favoring the development of resistance mutants within spatially structured biofilm communities. This suggests that biofilms may act as evolutionary incubators, in which medical interventions could unintentionally influence adaptation outcomes. Furthermore, the low-level resistance developing in treated biofilms may be overlooked in clinical settings and contribute to the selection of high-level resistant mutants. Our study, therefore, underscores that, in addition to dosing, optimizing the timing of antimicrobial treatment could mitigate the emergence of resistance. These principles are applicable beyond catheters to any biofilm-related infections where short-term antibiotic exposure may impact microbial community adaptation.

使用抗生素锁定疗法(ALT)来保护导管免受感染仍在争论中,因为其有效性不一致,并且有促进抗生素耐药性的潜在风险。利用儿童静脉通道的体外感染模型,我们证明了10天的持续治疗可以在体外根除大肠杆菌生物膜,而不会出现抗生素耐药性。相比之下,用于感染肠外营养患者的8小时间歇治疗在临床相关大鼠模型中快速选择体外和体内低水平的阿米卡星耐药突变,主要是由于fusA, sbmA和cpxA突变的趋同。我们的研究结果表明,间歇给药产生脉冲选择压力,有利于在空间结构的生物膜群落中抗性突变体的发展。这表明生物膜可能作为进化孵化器,其中医疗干预可能无意中影响适应结果。此外,在处理过的生物膜中产生的低水平耐药可能在临床环境中被忽视,并有助于选择高水平耐药突变体。因此,我们的研究强调,除了给药,优化抗菌药物治疗的时间可以减轻耐药性的出现。这些原则适用于导管以外的任何生物膜相关感染,其中短期抗生素暴露可能影响微生物群落的适应。
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引用次数: 0
Enzymes-enhanced antibiotic therapy reduces biofilms to undetectable levels in an implant-associated infection model. 在植入物相关感染模型中,酶增强抗生素治疗可将生物膜降低到无法检测的水平。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-16 DOI: 10.1038/s41522-026-00910-2
Randy Buzisa Mbuku, Hervé Poilvache, Loïc Maigret, Rita Vanbever, Françoise Van Bambeke, Olivier Cornu

Implant-associated infections caused by biofilm-forming bacteria, such as Staphylococcus aureus, remain a major clinical challenge due to their high tolerance to conventional antibiotic therapies. We report a dual-targeted therapeutic strategy that combines a tri-enzymatic cocktail designed to degrade key components of the biofilm matrix (TEC; comprising a DNA/RNA endonuclease, an endo-1,4-β-D-glucanase, and a β-N-acetylhexosaminidase), with vancomycin, both delivered via a thermosensitive poloxamer 407 hydrogel, for localized treatment of S. aureus biofilms. The formulation was evaluated both in vitro, on titanium-adherent biofilms, and in vivo, using a model of tissue cages containing titanium beads implanted in the back of guinea pigs. Animals additionally received intraperitoneal administration of vancomycin alone or combined with rifampicin. In vitro, this formulation enabled sequential drug release, with TEC delivered within the first 24 h and vancomycin for up to 96 h, and achieved >5 Log₁₀ reductions in CFU counts after two applications at 48 h interval. In vivo, biofilm-associated bacterial counts reached the detection limit (100 CFU; >5 Log10 decrease from the initial inoculum) in 75% of implants 1 day post-treatment and remained undetectable in 37.5% of them 5 days post-treatment, with no emergence of resistance. Treatment efficacy was reduced if TEC or vancomycin were omitted in the hydrogel or if rifampicin was not included in the intraperitoneal treatment. Vancomycin in the hydrogel also prevented the emergence of rifampicin resistance. These findings underscore the therapeutic potential of a dual-targeted approach, combining biofilm disruption with local sustained antibiotic release, to improve the management of implant-associated infections.

由生物膜形成细菌引起的种植体相关感染,如金黄色葡萄球菌,由于其对传统抗生素治疗的高耐受性,仍然是一个主要的临床挑战。我们报道了一种双靶向治疗策略,该策略结合了三酶混合物,旨在降解生物膜基质的关键成分(TEC;包括DNA/RNA内切酶,内切-1,4-β- d -葡聚糖酶和β- n -乙酰己糖苷酶)和万古霉素,两者都通过热敏波洛沙姆407水凝胶递送,用于金黄色葡萄球菌生物膜的局部治疗。该制剂在体外(钛粘附生物膜)和体内(植入豚鼠背部的含有钛珠的组织笼模型)进行了评估。动物在腹腔内单独或联合利福平给予万古霉素。在体外,该配方实现了药物的顺序释放,TEC在前24小时内释放,万古霉素最长可释放96小时,在间隔48小时的两次应用后,CFU计数减少了50 Log 1 0。在体内,治疗1天后,75%的种植体的生物膜相关细菌计数达到检出限(100 CFU,比初始接种量减少5 Log10),治疗5天后37.5%的种植体仍未检出,未出现耐药性。如果水凝胶中省略TEC或万古霉素,或腹膜内不使用利福平,则治疗效果降低。水凝胶中的万古霉素也阻止了利福平耐药性的出现。这些发现强调了双靶向方法的治疗潜力,结合生物膜破坏和局部持续抗生素释放,以改善种植体相关感染的管理。
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