Microbiological research最新文献_第5页

Combined transcriptome and microbiome characterization highlights digestive system development involved in the metabolism and immunity of the large yellow croaker (Larimichthys crocea) 转录组学和微生物组学的结合研究揭示了大黄鱼代谢和免疫过程中消化系统的发育

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-07 DOI: 10.1016/j.micres.2025.128394

Lizhen Li , Shaocong Huang , Zhiyi Bai , Hao Xu , Qun Ji , Wei Song

The development of the digestive system and its interaction with microbiota are critical for fish growth and health. Transcriptomic and 16S rRNA sequencing analyses were conducted to investigate the gene expression profiles of the digestive system and microbial community dynamics in Larimichthys crocea from the embryonic stage to day 28 to elucidate their potential roles in larval and juvenile development and their associations with immune and metabolic functions. The results revealed stage-specific changes in gene expression and microbial composition during development, and two critical transitional phases were identified: day 1 vs embryonic stage (C1 vs CE) and day 15 vs day 9 (C15 vs C9). Microbial succession demonstrated clear temporal characteristics: Pseudoalteromonas were dominant during the embryonic stage (CE), which was succeeded by Stenotrophomonas after hatching (C1, C3, C4, and C9), by Cohaesibacter on day 15 (C15), and by Psychrobacter as the core genus after formulated feed introduction on day 19. Functional enrichment analyses revealed predominant enrichment of differentially expressed genes in immune- and metabolic-related pathways, such as calcium signaling, steroid biosynthesis, and amino acid metabolism. Weighted gene co-expression network and correlation analyses revealed significant associations between specific genera (e.g., Rhodococcus and Psychrobacter) and immune- and metabolism-related genes. This study analyzed the developmental patterns of the digestive system of L. crocea and revealed significant correlations between shifts in the microbiota and host metabolism and immunity, highlighting the close association between the microbiota and metabolic and immune responses.

消化系统的发育及其与微生物群的相互作用对鱼类的生长和健康至关重要。通过转录组学和16S rRNA测序分析，研究了胭脂鱼（Larimichthys crocea）从胚胎期到第28天消化系统和微生物群落动态的基因表达谱，以阐明其在幼虫和幼鱼发育中的潜在作用及其与免疫和代谢功能的关联。结果揭示了发育过程中基因表达和微生物组成的阶段性变化，并确定了两个关键过渡阶段：第1天与胚胎期（C1 vs CE）和第15天与第9天（C15 vs C9）。微生物演替表现出明显的时间特征：假互变单胞菌在胚胎期（CE）占主导地位，孵化后为窄养单胞菌（C1、C3、C4和C9），第15天为Cohaesibacter (C15)，第19天引入配方饲料后为Psychrobacter成为核心属。功能富集分析显示，差异表达基因主要富集于免疫和代谢相关途径，如钙信号、类固醇生物合成和氨基酸代谢。加权基因共表达网络和相关分析显示，特定属（如红球菌和冷杆菌）与免疫和代谢相关基因之间存在显著关联。本研究分析了羊草消化系统的发育模式，揭示了微生物群的变化与宿主代谢和免疫之间的显著相关性，强调了微生物群与代谢和免疫应答之间的密切联系。

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引用次数: 0

The gut microbiota in post-stroke depression: A systematic review of microbial mechanisms and therapeutic targeting of neuroinflammation 脑卒中后抑郁的肠道微生物群：微生物机制和神经炎症治疗靶向的系统综述。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-06 DOI: 10.1016/j.micres.2025.128391

Qianwen Zhang , Shiqing Zhang , Xingqin Cao , Yinghao Zhi , Ying Guo

Post-stroke depression (PSD), a frequent and debilitating complication after stroke, severely hinders rehabilitation. Emerging evidence underscores the role of neuroinflammation and the gut microbiota in PSD pathogenesis. This review systematically elaborates the mechanisms by which gut dysbiosis contributes to PSD-related neuroinflammation via immune cell regulation (e.g., Treg/Th17 balance), microbial metabolites (e.g., SCFAs, tryptophan derivatives), and neural pathways (vagus nerve, HPA axis). A key focus is the comparative analysis of the gut microbiota in PSD against major depressive disorder (MDD) and Alzheimer's disease (AD), revealing a unique, stroke-induced microbial signature characterized by a loss of protective symbionts and a bloom of pro-inflammatory taxa. We further discuss the translational potential of microbiota-targeted interventions (e.g., probiotics, prebiotics) for PSD. By integrating clinical microbial ecology with mechanistic insights, this review synthesizes evidence suggesting that the gut microbiome may represent a promising diagnostic and therapeutic target for PSD, offering a distinct perspective from previous literature.

卒中后抑郁（PSD）是卒中后常见的并发症，严重阻碍康复。新出现的证据强调了神经炎症和肠道微生物群在PSD发病机制中的作用。本综述系统阐述了肠道生态失调通过免疫细胞调节（如Treg/Th17平衡）、微生物代谢物（如scfa、色氨酸衍生物）和神经通路（迷走神经、HPA轴）促进psd相关神经炎症的机制。一个关键的焦点是PSD对重度抑郁症（MDD）和阿尔茨海默病（AD）的肠道微生物群的比较分析，揭示了一种独特的，中风诱导的微生物特征，其特征是保护性共生体的丧失和促炎类群的大量繁殖。我们进一步讨论了针对微生物群的干预措施（如益生菌，益生元）对PSD的转化潜力。通过将临床微生物生态学与机制见解相结合，本综述综合证据表明肠道微生物组可能代表PSD的有希望的诊断和治疗靶点，提供了与以往文献不同的视角。

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引用次数: 0

The hidden players: The mycobiome of pancreatic ductal adenocarcinoma tumors 隐藏的玩家：胰腺导管腺癌肿瘤的菌群

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-05 DOI: 10.1016/j.micres.2025.128392

Estrin Camille , Bertout Sébastien, Bellet Virginie

The microorganisms that inhabit the human body are known to play a role in human health and disease. Continuing to elucidate their specific role in disease progression is, however, necessary. The imbalance of these microorganisms–known as dysbiosis–has been linked to a myriad of intestinal diseases, and more recently to cancer. Despite making up less than 0.1 % of the human microbiome, dysbiosis of the fungal component of the microbiome—the mycobiome—has been found to contribute to the tumorigenesis and progression of certain types of tumors, pancreatic ductal adenocarcinoma (PDAC) included. The quantity and composition of the mycobiome was found to differ between healthy pancreatic tissue, the gut mycobiome of PDAC patients and PDAC tissue. Moreover, in a murine model of PDAC, it was shown that fungal ablation had a protective effect on tumor growth, and that specific fungal species, such as Malassezia globosa, contribute to tumor growth as well as to the inflammatory environment observed in PDAC tumors which promotes tumor progression. Research shows that fungal presence contributes to shaping the immune microenvironment through the activation of the complement system and/or by eliciting a type 2 immune response. Despite these preliminary findings, given the novelty of the field and of the bioinformatics pipelines used to analyze sequencing data, standardized approaches are still under development, thus leading to disagreement on the reliability of these results. The purpose of this review is to provide an up-to-date overview of the current research regarding the contribution of the fungal mycobiome in PDAC tumor progression and the overall tumor microenvironment (TME) of PDAC tumors.

众所周知，居住在人体中的微生物在人类健康和疾病中起着重要作用。然而，继续阐明它们在疾病进展中的具体作用是必要的。这些微生物的失衡——被称为生态失调——与无数的肠道疾病有关，最近还与癌症有关。尽管在人类微生物组中所占比例不到0.1% %，但微生物组的真菌成分——真菌组——的生态失调已被发现有助于某些类型肿瘤的发生和进展，包括胰腺导管腺癌（PDAC）。发现健康胰腺组织、PDAC患者肠道菌群和PDAC组织之间的菌群数量和组成存在差异。此外，在PDAC小鼠模型中，研究表明真菌消融对肿瘤生长具有保护作用，并且在PDAC肿瘤中观察到的特定真菌物种，如马拉色菌，促进肿瘤生长和炎症环境，从而促进肿瘤进展。研究表明，真菌的存在有助于通过激活补体系统和/或引发2型免疫反应来塑造免疫微环境。尽管有这些初步发现，鉴于该领域的新颖性和用于分析测序数据的生物信息学管道，标准化方法仍在开发中，因此导致对这些结果的可靠性存在分歧。这篇综述的目的是提供关于真菌菌群在PDAC肿瘤进展和PDAC肿瘤整体微环境（TME）中的贡献的最新研究综述。

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引用次数: 0

Bacteroides acidifaciens alleviates high-fat diet-induced obesity-related osteoporosis by regulating gut microbiota and bile acid metabolism via the gut-bone axis 酸化拟杆菌通过肠-骨轴调节肠道菌群和胆汁酸代谢，减轻高脂肪饮食引起的肥胖相关骨质疏松症

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-05 DOI: 10.1016/j.micres.2025.128393

Cihua Zheng , Jian Xie , Furui Tang , Zhuoya Wang , Li Liu , Yimin Pi , Yuchun Zhong , Zhidong He , Tian Liu , Jiacheng Zheng , Jun Luo

Obesity disrupts bone formation-resorption balance. Despite the established role of Bacteroides acidifaciens (B. acidifaciens) in modulating metabolic homeostasis, reducing inflammation, and improving lipid metabolism, its impact on obesity-associated osteoporosis is still not well understood. In this study, we delved into the potential protective influence of B. acidifaciens on high-fat diet (HFD) induced bone loss. The results showed that B. acidifaciens sharply improved weight gain, glucose and lipid metabolism in 16 weeks HFD mice. Both In vitro and in vivo experiments have conclusively demonstrated that the introduction of B. acidifaciens notably ameliorated the imbalance of HFD induced osteogenesis and osteoclastogenesis. B. acidifaciens also regulated HFD induced gut microbiota and bile acid metabolism, and strengthened intestinal mucosal barrier function. Additionally, B. acidifaciens significantly activated the AMPK-PPARα signaling pathway in bone tissue. Thus, our study indicated that B. acidifaciens regulated metabolism, restored gut microbiota balance, and activated AMPK-PPARα pathway to prevent HFD-induced bone loss, potentially aiding in preventing and treating obesity-related osteoporosis.

肥胖会破坏骨形成-吸收平衡。尽管酸化拟杆菌（B. acidifaciens）在调节代谢稳态、减少炎症和改善脂质代谢方面的作用已被确立，但其对肥胖相关骨质疏松症的影响仍未得到很好的了解。在这项研究中，我们深入研究了酸化芽杆菌对高脂肪饮食（HFD）引起的骨质流失的潜在保护作用。结果表明，增酸芽孢杆菌能显著改善16周HFD小鼠的增重、糖脂代谢。体外和体内实验均明确表明，引入酸化芽胞杆菌可显著改善HFD诱导的成骨和破骨细胞生成的不平衡。B.酸化菌还能调节HFD诱导的肠道菌群和胆汁酸代谢，增强肠黏膜屏障功能。此外，酸化芽胞杆菌显著激活骨组织AMPK-PPARα信号通路。因此，我们的研究表明，酸化芽胞杆菌可调节代谢，恢复肠道菌群平衡，激活AMPK-PPARα通路，预防hfd诱导的骨质流失，可能有助于预防和治疗肥胖相关性骨质疏松症。

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引用次数: 0

Co-regulation of HexC fine-tunes HexA-dependent transcription and acid stress response in Pectobacterium carotovorum 在胡萝卜乳杆菌中，HexC的协同调控微调了hexa依赖的转录和酸胁迫反应

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-04 DOI: 10.1016/j.micres.2025.128389

Eunhye Goo , Serim Lee , Jae Hoon Lee

Environmental fluctuations and host-derived stresses demand precise transcriptional regulation in bacterial pathogens to ensure survival and pathogenic success. In Pectobacterium sp., causal agents of soft rot disease, the global regulator HexA is known to repress genes involved in plant cell wall-degrading enzyme (PCWDE) production, quorum sensing (QS), and virulence. However, its broader regulatory scope and physiological significance remain poorly understood. Here, we examined HexA function in P. carotovorum PCC27 through integrated ChIP-seq and RNA-seq analyses, revealing that HexA controls a diverse regulon, including transcriptional regulators, hypothetical proteins, and post-transcriptional regulators such as RsmA and RsmB. Among the newly identified targets, HexC, previously annotated as a hypothetical protein, was identified as a co-regulator that physically interacts with HexA and increases its DNA-binding affinity. Biochemical and genetic analyses demonstrated that HexC reinforces HexA-mediated transcriptional repression. The hexA/hexC double mutant produced higher levels of QS signals than the hexA single mutant but did not exhibit further increase in virulence. Phenotypic assays showed that the hexA/hexC mutant exhibited reduced fitness under acidic conditions yet outcompeted the wild-type at neutral pH in LB medium. However, in planta, the hexA, hexC, and hexA/hexC mutants consistently displayed reduced competitiveness compared to the wild-type in both single and mixed infections. These findings establish HexC as a co-repressor that fine-tunes HexA activity, providing mechanistic insights into how transcriptional regulation evolves to balance virulence and environmental fitness.

环境波动和宿主来源的压力需要细菌病原体精确的转录调控，以确保生存和致病成功。在软腐病的致病因子Pectobacterium sp.中，已知全局调节因子HexA抑制参与植物细胞壁降解酶（PCWDE）产生、群体感应（QS）和毒力的基因。然而，其更广泛的调控范围和生理意义仍然知之甚少。在这里，我们通过集成ChIP-seq和RNA-seq分析检测了HexA在p.c rotovorum PCC27中的功能，揭示了HexA控制着多种调控，包括转录调控因子、假设蛋白和转录后调控因子，如RsmA和RsmB。在新发现的靶点中，HexC，以前被注释为一种假设的蛋白质，被确定为与HexA物理相互作用并增加其dna结合亲和力的共同调节因子。生化和遗传分析表明，HexC增强了hexa介导的转录抑制。hexA/hexC双突变体比hexA单突变体产生更高水平的QS信号，但毒力没有进一步增加。表型分析表明，hexA/hexC突变体在酸性条件下适应性降低，但在中性pH的LB培养基中优于野生型。然而，在植物中，与野生型相比，在单一和混合感染中，hexA、hexC和hexA/hexC突变体始终表现出较低的竞争力。这些发现确定了HexC作为一种协同抑制因子，可以微调HexA的活性，为转录调控如何进化以平衡毒力和环境适应性提供了机制上的见解。

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引用次数: 0

Meningitic Escherichia coli disrupts the blood-brain barrier through pyroptosis and tight junction degradation and NLRP6 deficiency aggravates infection outcomes 脑膜炎大肠杆菌通过热亡和紧密连接降解破坏血脑屏障，NLRP6缺乏会加重感染结果

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-04 DOI: 10.1016/j.micres.2025.128388

Kaixiang Jia , Yangyang Du , Xinrui Cao , Xin Shen , Jinrong Ran , Yi Lu , Lianci Peng , Zhiwei Li , Rendong Fang

Extraintestinal pathogenic Escherichia coli (ExPEC) can cause meningitis by breaching the blood-brain barrier (BBB), but the underlying mechanisms remain unclear. In this study, we found that meningitic ExPEC disrupts the BBB through two distinct mechanisms: inducing endothelial pyroptotic cell death and disrupting tight junction (TJ) proteins. Transcriptomic analysis revealed activation of cell death pathways and suppression of tight junction signaling in ExPEC-stimulated human cerebral microvascular endothelial cells (hCMEC/D3). ExPEC infection induced pyroptotic cell death characterized by caspase-1 and GSDMD activation, along with inflammatory cytokine production. Additionally, ExPEC reduced TJ protein expression and disrupted their continuous distribution. Based on transcriptomic results showing simultaneous activation of NLR and TLR pathways, we investigated the role of NLRP6, a unique receptor with dual functions. Silencing NLRP6 in hCMECs exacerbated ExPEC-induced TJ protein disruption but reduced pyroptotic cell death. In vivo experiments indicated that NLRP6^-/- mice showed accelerated mortality, higher bacterial loads, more severe brain tissue damage, enhanced TJ protein disruption, and elevated inflammatory cytokines following ExPEC infection. Brain transcriptomic analysis revealed that NLRP6 deficiency resulted in impaired immune function, downregulation of tight junction pathways, and upregulation of neurological dysfunction-related pathways. These results demonstrate that meningitic ExPEC promotes bacterial meningitis through dual BBB disruption mechanisms, and NLRP6 plays a crucial protective role by maintaining BBB integrity during infection.

肠外致病性大肠杆菌（ExPEC）可通过破坏血脑屏障（BBB）引起脑膜炎，但其潜在机制尚不清楚。在这项研究中，我们发现脑膜炎exic通过两种不同的机制破坏血脑屏障：诱导内皮细胞死亡和破坏紧密连接（TJ）蛋白。转录组学分析显示，在u - u刺激的人大脑微血管内皮细胞（hCMEC/D3）中，细胞死亡途径被激活，紧密连接信号被抑制。exic感染可诱导以caspase-1和GSDMD激活为特征的热亡细胞死亡，并伴有炎性细胞因子的产生。此外，ExPEC降低了TJ蛋白的表达，破坏了它们的连续分布。基于NLR和TLR通路同时激活的转录组学结果，我们研究了NLRP6这一具有双重功能的独特受体的作用。在hCMECs中沉默NLRP6加重了eu诱导的TJ蛋白破坏，但减少了热腐细胞死亡。体内实验表明，NLRP6-/-小鼠在ExPEC感染后表现出死亡加速、细菌负荷增加、脑组织损伤更严重、TJ蛋白破坏增强和炎症细胞因子升高。脑转录组学分析显示，NLRP6缺乏导致免疫功能受损，紧密连接通路下调，神经功能障碍相关通路上调。这些结果表明，脑膜炎exic通过双重血脑屏障破坏机制促进细菌性脑膜炎，而NLRP6在感染期间通过维持血脑屏障完整性发挥重要的保护作用。

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引用次数: 0

Microbiome based precision medicine through integrated multiomics and machine learning 结合多组学和机器学习的基于微生物组的精准医学。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-03 DOI: 10.1016/j.micres.2025.128384

Abhishek Kumar , Caiming Xu , Tikam Chand Dakal

Gut microbiome (GME) is a dynamic ecosystem composed of diverse microorganisms with extensive functional potential that influence host physiology, endocrinology, and neurology. This review explores how multiomics (m^OMICS) and machine learning (ML) enhance understanding of the GME and its implications for human disease and therapy. Integrating metagenomics, metatranscriptomics, metaproteomics, and metabolomics with ML enables the linkage of microbial composition and function to clinical outcomes. Combined m^OMICS approaches elucidate species and strain dynamics, metabolic pathways, and metabolite production within the gut environment. Techniques such as shotgun metagenomics, metagenome-assembled genomes, and pathway mapping reveal associations between dysbiosis and diseases including inflammatory bowel disease, colorectal cancer, cardiometabolic, and neurological disorders. Mechanistic insights highlight short-chain fatty acids in immune regulation, bile acid transformations in metabolic signaling, and trimethylamine N-oxide in cardiovascular risk. ML models trained on heterogeneous datasets identify disease-related microbial modules, improve patient stratification, and predict therapeutic responses, such as differentiating IBD subtypes and detecting cancer-linked microbial signatures. Network analyses uncover gut microbial interaction patterns influencing host physiology. Emerging integrative tools like MOFA+ , DIABLO, and MintTea strengthen cross-modal analysis and biomarker discovery. Standardized workflows addressing quality control, assembly, binning, annotation, and visualization ensure reproducibility. Together, m^OMICS and ML establish a robust framework for translating GME ecology into clinically relevant biomarkers and precision interventions. To enhance reliability, GME studies should adopt uniform sampling protocols, correct compositional biases, employ interpretable models, and validate findings across multi-site cohorts to advance microbiome-based diagnostics and therapeutics in precision medicine.

肠道微生物组（Gut microbiome， GME）是一个由多种微生物组成的动态生态系统，具有广泛的功能潜力，影响宿主生理、内分泌和神经学。这篇综述探讨了多组学（mOMICS）和机器学习（ML）如何增强对GME的理解及其对人类疾病和治疗的影响。将宏基因组学、亚转录组学、宏蛋白质组学和代谢组学与ML相结合，可以将微生物组成和功能与临床结果联系起来。结合mOMICS方法阐明物种和菌株动力学，代谢途径和肠道环境中的代谢物生产。诸如散弹枪宏基因组学、宏基因组组装基因组和途径制图等技术揭示了生态失调与包括炎症性肠病、结直肠癌、心脏代谢和神经系统疾病在内的疾病之间的关联。机制方面的见解强调了短链脂肪酸在免疫调节中的作用，胆汁酸转化在代谢信号传导中的作用，以及三甲胺n -氧化物在心血管风险中的作用。在异构数据集上训练的ML模型可以识别疾病相关的微生物模块，改善患者分层，并预测治疗反应，例如区分IBD亚型和检测癌症相关的微生物特征。网络分析揭示了影响宿主生理的肠道微生物相互作用模式。新兴的综合工具如MOFA+ 、DIABLO和MintTea加强了跨模态分析和生物标志物的发现。处理质量控制、装配、分组、注释和可视化的标准化工作流确保了再现性。mOMICS和ML共同建立了一个强大的框架，将GME生态学转化为临床相关的生物标志物和精确干预措施。为了提高可靠性，GME研究应采用统一的采样方案，纠正组成偏差，采用可解释的模型，并在多地点队列中验证研究结果，以推进精准医学中基于微生物组的诊断和治疗方法。

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引用次数: 0

mgrB inactivation confers enhanced pathogenicity and immune evasion over mcr-1 expression in colistin-resistant Klebsiella pneumoniae mgrB失活对耐粘菌素肺炎克雷伯菌的致病性和免疫逃避作用强于mcr-1表达。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-01 DOI: 10.1016/j.micres.2025.128386

Zhuoren Ling , Ruicheng Zheng , Yanjun Dong , Wenjuan Yin , Lu Qiao , Rong Zhang , Pramod K. Jangir , Qiaoling Sun , Gerald Larrouy-Maumus , Craig MacLean , Yang Wang , Jianzhong Shen , Timothy R. Walsh

Colistin is one of the last treatment options against human infections caused by multi-drug resistant Klebsiella pneumoniae. Colistin resistant K. pneumoniae arises through modifying bacterial lipopolysaccharide (LPS) via two mechanisms: the mgrB inactivation on chromosome and mcr-1 expression - usually plasmid-mediated. Notably, chromosomal-mediated resistance is more common in naturally-occurring clinical K. pneumoniae than plasmid-borne resistance. Herein we demonstrated that K. pneumoniae strain with a mutant mgrB (ΔmgrB) gene exhibited increased pathogenicity compared to those carrying mcr-1, as evidenced in Galleria mellonella and murine bacteraemia model. Strain possessing ΔmgrB showed higher mortality rate, greater bacterial accumulation, and increased damage to host tissue. Although both ΔmgrB and mcr-1 impose fitness cost on K. pneumoniae and enhance bacterial evasion from phagocytosis, ΔmgrB mediated greater bacterial resistance to host defence peptides than mcr-1, providing an evolutionary advantage. These findings indicated distinct features of mgrB-inactivated K. pneumoniae and mcr-1-positive K. pneumoniae in host immunity responses, and promote understanding of how antibiotic-resistant determinants influence host-pathogens interactions.

粘菌素是对抗多重耐药肺炎克雷伯菌引起的人类感染的最后治疗选择之一。耐粘菌素肺炎克雷伯菌是通过修饰细菌脂多糖（LPS）的两种机制产生的：染色体上的mgrB失活和mcr-1的表达-通常是质粒介导的。值得注意的是，在自然发生的临床肺炎克雷伯菌中，染色体介导的耐药性比质粒传播的耐药性更常见。在本文中，我们证明了携带突变mgrB （ΔmgrB）基因的肺炎克雷伯菌株比携带mcr-1的肺炎克雷伯菌株具有更高的致病性，这在mellonella Galleria和小鼠菌血症模型中得到了证明。含有ΔmgrB的菌株显示出更高的死亡率，更大的细菌积聚和对宿主组织的损害增加。虽然ΔmgrB和mcr-1都增加了肺炎克雷伯菌的适应性成本，并增强了细菌对吞噬的逃避，但ΔmgrB介导的细菌对宿主防御肽的抗性比mcr-1更强，这提供了进化优势。这些发现表明mgrb灭活肺炎克雷伯菌和mcr-1阳性肺炎克雷伯菌在宿主免疫反应中的独特特征，并促进了对抗生素耐药决定因素如何影响宿主-病原体相互作用的理解。

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引用次数: 0

Coordinated host resistance and distinct phage strategies shape biofilm-phage dynamics in Pseudomonas aeruginosa 协调宿主耐药性和不同噬菌体策略形成铜绿假单胞菌生物膜-噬菌体动力学。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-11-01 DOI: 10.1016/j.micres.2025.128385

Ganghua Han , Lei Zhao , Ruixin Li , Ruihua Liu , Yingying Wang , Mark Bartlam

Temperate and virulent phages coexist in natural environments and can collaboratively contribute to the lysis of bacterial biofilms. However, their therapeutic potential and the dynamics of phage-biofilm interactions, particularly in clinical contexts, remain poorly understood. In this study, we demonstrated the strong biofilm-lysing capabilities of the temperate phage PaoP1 and virulent phage PaoP5 against Pseudomonas aeruginosa biofilms, highlighting their potential for phage therapy. RNA-seq analysis revealed a shared host resistance mechanism involving the downregulation of flagellar biosynthesis and enhanced biofilm formation. Despite this common host response, the two phages exhibited distinct infection strategies: PaoP1 integrated quiescently into the host genome, while PaoP5 rapidly and abundantly expressed its genes, potentially hijacking the host transcriptional machinery through an as-yet-unknown mechanism. These findings deepen our understanding of phage-biofilm interactions and support the development of phage-based approaches to treat biofilm-associated infections.

温带和强毒噬菌体在自然环境中共存，并能协同促进细菌生物膜的裂解。然而，它们的治疗潜力和噬菌体-生物膜相互作用的动力学，特别是在临床环境中，仍然知之甚少。在这项研究中，我们证明了温带噬菌体PaoP1和强毒噬菌体PaoP5对铜绿假单胞菌生物膜的强生物膜裂解能力，突出了它们在噬菌体治疗方面的潜力。RNA-seq分析揭示了一个共同的宿主抗性机制，包括下调鞭毛生物合成和增强生物膜形成。尽管有这种共同的宿主反应，但这两种噬菌体表现出不同的感染策略：PaoP1静默地整合到宿主基因组中，而PaoP5快速而丰富地表达其基因，可能通过一种尚不清楚的机制劫持宿主的转录机制。这些发现加深了我们对噬菌体-生物膜相互作用的理解，并支持了基于噬菌体治疗生物膜相关感染的方法的发展。

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引用次数: 0

DNA damage-regulated autophagy modulator 1 (DRAM1)-induced lipophagy facilitates Toxoplasma gondii nutrient acquisition and infection DNA损伤调节的自噬调节因子1 （DRAM1）诱导的脂噬促进了弓形虫的营养获取和感染。

IF 6.9 1区生物学 Q1 MICROBIOLOGY

Microbiological research

Pub Date : 2025-10-30 DOI: 10.1016/j.micres.2025.128383

Yongheng Hou , Shiguang Huang , Xin-zhuan Su , Fangli Lu

Autophagy is a catabolic process that responds to various environmental stresses, such as nutrient deficiency and intracellular pathogen infection. Toxoplasma gondii is an intracellular parasite that acquires nutrients from the host cells for its proliferation; however, the molecular mechanisms of T. gondii parasites’ nutritional acquisition and metabolism are not fully understood. Here, we found that T. gondii type I RH strain induced host cell autophagy for nutrient acquisition and growth. T. gondii RH strain infection induced DNA damage-regulated autophagy modulator 1 (DRAM1) expression in host cells, and mechanistic analyses suggest an involvement of the IL-33-MyD88-p38/NF-κB signaling pathway in this process. DRAM1 knockdown decreased T. gondii parasite growth, while DRAM1 overexpression increased T. gondii parasite growth by hyperactivating autophagy, especially lipophagy, to provide fatty acids for T. gondii proliferation, which led to increased tissue pathology. This study identified DRAM1 as a critical molecule in regulating type I T. gondii-induced lipophagy, parasite proliferation, and liver pathology in mice. The results provide crucial insights into how T. gondii leverages host autophagy for its gain and identify a target for potential disease management, which may offer new avenues for developing novel drugs against this parasite.

自噬是一种对各种环境胁迫（如营养缺乏和细胞内病原体感染）作出反应的分解代谢过程。刚地弓形虫是一种细胞内寄生虫，从宿主细胞中获取营养以增殖；然而，弓形虫的营养获取和代谢的分子机制尚不完全清楚。在这里，我们发现弓形虫I型RH菌株诱导宿主细胞自噬以获取营养和生长。弓形虫RH感染诱导宿主细胞DNA损伤调节的自噬调节因子1 （DRAM1）表达，机制分析提示IL-33-MyD88-p38/NF-κB信号通路参与了这一过程。DRAM1敲低使弓形虫生长下降，而DRAM1过表达通过过度激活自噬，特别是脂噬，为弓形虫增殖提供脂肪酸，从而促进弓形虫生长，导致组织病理增加。本研究发现，DRAM1是调节小鼠I型弓形虫诱导的脂肪吞噬、寄生虫增殖和肝脏病理的关键分子。这些结果为弓形虫如何利用宿主自噬获得自身利益提供了重要见解，并确定了潜在疾病管理的靶标，这可能为开发针对这种寄生虫的新药提供新的途径。

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引用次数: 0