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RmpA drives metabolic reprogramming to modulate the phenotypic switch between hypermucoviscosity and biofilm formation in hypervirulent Klebsiella pneumoniae RmpA驱动代谢重编程，以调节高致病性肺炎克雷伯菌高黏性和生物膜形成之间的表型转换

hLife

Pub Date : 2025-10-01 DOI: 10.1016/j.hlife.2025.06.005

Shigang Yao , Jiangqing Huang , Jianing Geng , Dawei Wei , Chao Wang , Yuqin Song , Gang Zhang , Jie Feng

Hypervirulent Klebsiella pneumoniae (hvKp) is a major cause of severe community-acquired infection. A key plasmid-encoded factor, regulator of mucoid phenotype A (RmpA), activates capsule locus gene expression to promote hypermucoviscosity, a phenotype that is strongly linked to increased pathogenicity. However, the precise regulatory mechanisms that control RmpA in hvKp remain poorly understood. In this study, we constructed a rmpA knockdown strain in hvKp using CRISPR interference and assessed the global regulatory role of RmpA through complementary multi-omic sequencing (RNA sequencing [RNA-seq] and chromatin immunoprecipitation sequencing [ChIP-seq]), promoter-gfp reporter assays, and phenotypic experiments. The functional role of RmpA was evaluated in Escherichia coli via heterologous expression. The RNA-seq analysis revealed that RmpA activates carbohydrate metabolism pathways, but represses pathways related to DNA replication, ribosome metabolism, and biofilm formation. The ChIP-seq analysis further confirmed the potential role of RmpA as a global regulator that enhances capsule production by activating transcripts within the capsule locus. It also upregulates genes involved in sugar metabolism and transport, which supplies essential precursors for capsule synthesis. RmpA modulates the phenotypic switch between hypermucoviscosity and biofilm formation by repressing type III fimbriae genes. Notably, RmpA overexpression in E. coli induced changes in multiple metabolic pathways. These findings position RmpA as a latent central regulator in hvKp that orchestrates the metabolic pathways and phenotypic traits essential for virulence.

高毒力肺炎克雷伯菌（hvKp）是严重社区获得性感染的主要原因。一个关键的质粒编码因子，黏液样表型A （RmpA）的调节因子，激活胶囊位点基因表达以促进高黏液粘度，这种表型与增加的致病性密切相关。然而，在hvKp中控制RmpA的精确调控机制仍然知之甚少。在本研究中，我们利用CRISPR干扰构建了hvKp中rmpA敲低菌株，并通过互补多组测序（RNA测序[RNA-seq]和染色质免疫沉淀测序[ChIP-seq]）、启动子-gfp报告子测定和表型实验评估了rmpA的全球调控作用。通过外源表达，对RmpA在大肠杆菌中的功能作用进行了评价。RNA-seq分析显示，RmpA激活碳水化合物代谢途径，但抑制与DNA复制、核糖体代谢和生物膜形成相关的途径。ChIP-seq分析进一步证实了RmpA作为一种全局调节剂的潜在作用，它通过激活胶囊位点内的转录本来促进胶囊的生产。它还上调参与糖代谢和运输的基因，这为胶囊合成提供了必要的前体。RmpA通过抑制III型菌膜基因调节高黏性和生物膜形成之间的表型转换。值得注意的是，RmpA在大肠杆菌中的过表达诱导了多种代谢途径的变化。这些发现表明RmpA在hvKp中是一个潜在的中枢调节因子，它协调了代谢途径和毒力所必需的表型特征。

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引用次数: 0

Crucial functions of gut microbiota on gut–liver repair 肠道菌群在肠肝修复中的关键功能

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2025.01.001

Yamei Wang , Huining Yan , Qianqian Zheng , Xun Sun

The gut microbiota exert a critical influence on the gut–liver axis by facilitating intestinal and hepatic repair via intricate bidirectional mechanisms. Inflammatory bowel disease (IBD), metabolic-associated steatohepatitis (MASH), and the gut–liver axis exemplify the complex interplay between the gut microbiota and hepatic function. This review explores the interplay between microbial metabolites and their roles in maintaining intestinal integrity and promoting liver regeneration. Emerging evidence shows that gut microbiota support intestinal and liver health by modulating immune responses via microbial metabolites and interactions with host immune cells. Moreover, advances in personalized therapies, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), could potentially restore microbial balance and enhance tissue repair. Understanding these relationships presents opportunities for innovative interventions to improve gut and liver health, particularly in individuals with metabolic disorders.

肠道微生物群通过复杂的双向机制促进肠道和肝脏修复，对肠肝轴产生关键影响。炎症性肠病（IBD）、代谢相关脂肪性肝炎（MASH）和肠-肝轴是肠道微生物群和肝功能之间复杂相互作用的例证。本文综述了微生物代谢产物之间的相互作用及其在维持肠道完整性和促进肝脏再生中的作用。新出现的证据表明，肠道微生物群通过微生物代谢物和与宿主免疫细胞的相互作用调节免疫反应，从而支持肠道和肝脏健康。此外，个性化治疗的进步，包括益生菌、益生元和粪便微生物群移植（FMT），可能会恢复微生物平衡，增强组织修复。了解这些关系为创新干预提供了机会，以改善肠道和肝脏健康，特别是对代谢紊乱的个体。

引用次数: 0

Histoplasmosis misdiagnosed as malignancies in immunocompetent and immunocompromised patients 免疫功能正常和免疫功能低下患者中被误诊为恶性肿瘤的组织胞浆菌病：临床表现、放射学和病理学发现的全球视角

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2024.07.001

Ofonime E. Benjamin , Thelma E. Bassey , Chimaobi I. Nwagboso , Asukwo Onukak , Anthony C. Nlemadim , Bernard B. Akpu , David Elem , Bassey E. Ekeng

引用次数: 0

Candida albicans overgrowth impairs anti-PD-1 immunotherapy in oral tumor-bearing mice 白色念珠菌过度生长损害口腔荷瘤小鼠抗pd -1免疫治疗

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2024.12.004

Xu Wang , Xinming Zhang , Shuangshuang Wu , Zhimin Yan

引用次数: 0

Dissection of intratumor microbiome–host interactions at the single-cell level in lung cancer 肺癌单细胞水平肿瘤内微生物-宿主相互作用的解剖

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2024.09.001

Yong-Jing Ma , Yuan-Chen Sun , Lu Wang , Wan-Xing Xu , Xiao-Dan Fan , Jun Ding , Christopher Heeschen , Wen-Juan Wu , Xiao-Qi Zheng , Ning-Ning Liu

The intratumor microbiome, one of the hallmarks of cancer, plays a crucial role in cancer progression through its interaction with the host. However, the underlying mechanisms remain poorly understood. In this study, six publicly available single-cell transcriptomic lung cancer datasets (comprising 178 samples) from multiple centers (Shanghai, New York, Seoul) were integrated to investigate the heterogeneity of host–microbiome interactions at the single-cell level using single-cell analysis of host–microbiome interactions (SAHMI). The results indicate that primary tumor tissues have a high proportion of fungi-associated cells, whereas metastatic brain tissues predominantly contain bacteria-associated cells. There are also distinct microbial distributions across cell types. Notably, the presence of specific bacteria significantly influences the transcriptome of resident host cells, including T cells and macrophages, by modulating pathways related to ribosomal RNA (rRNA) processing, cellular responses to stress and stimuli, and RNA and protein metabolism. Finally, specific cell-associated bacteria are significantly correlated with clinical features, such as lung cancer stages and smoking frequency. These single-cell insights into microbiome–host interactions improve current understanding about lung cancer development and progression and offer potential micro-ecological and diagnostic insights.

肿瘤内微生物组是癌症的标志之一，通过与宿主的相互作用在癌症进展中起着至关重要的作用。然而，潜在的机制仍然知之甚少。在这项研究中，我们整合了来自多个研究中心（上海、纽约、首尔）的6个公开的单细胞转录组肺癌数据集（包括178个样本），利用宿主-微生物组相互作用的单细胞分析（SAHMI），在单细胞水平上研究宿主-微生物组相互作用的异质性。结果表明，原发肿瘤组织中真菌相关细胞的比例很高，而转移性脑组织中主要含有细菌相关细胞。在不同的细胞类型中也有不同的微生物分布。值得注意的是，特定细菌的存在通过调节与核糖体RNA （rRNA）加工、细胞对应激和刺激的反应以及RNA和蛋白质代谢相关的途径，显著影响常驻宿主细胞（包括T细胞和巨噬细胞）的转录组。最后，特异性细胞相关细菌与临床特征显著相关，如肺癌分期和吸烟频率。这些对微生物-宿主相互作用的单细胞见解提高了目前对肺癌发生和进展的理解，并提供了潜在的微生态和诊断见解。

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引用次数: 0

Skin microbiome dysbiosis in Prototheca wickerhamii infection wickerhamii原鞘感染的皮肤微生物群失调

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2025.03.001

Yan Zhang , Jian Guo , Runze Zhu , Liang Hu , Teng Li , Xiaoli Cao , Han Shen , Wenjuan Wu

引用次数: 0

778th Xiangshan Science Conference convenes experts to explore breakthroughs in lung and respiratory mucosal immunity 第778届香山科学大会汇聚专家，探讨肺与呼吸粘膜免疫的新突破

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2025.04.006

Qun Yan , Shuo Wang , Yi Shi

引用次数: 0

Advancing global antifungal development to combat invasive fungal infection 推进全球抗真菌药物研发，对抗侵袭性真菌感染

hLife

Pub Date : 2025-08-01 DOI: 10.1016/j.hlife.2025.06.001

Xiu-Li Wang , Jun Ding , Koon Ho Wong , Chen Ding , Chang-Bin Chen , Wen-Juan Wu , Ning-Ning Liu

引用次数: 0

Addressing COVID-19 vaccination hesitancy through community engagement and integration with primary health care services in Wakiso district, Uganda 乌干达瓦基索地区通过社区参与和初级卫生保健服务整合解决COVID-19疫苗接种犹豫问题

hLife

Pub Date : 2025-06-05 DOI: 10.1016/j.hlife.2025.05.012

David Musoke, Paineto Masengere, Allan Ssembuusi, Keneth Sebukeera, Filimin Niyongabo, Carol Nabbanja, Shafik Senkubuge, Grace B. Lubega, Rhoda K. Wanyenze

引用次数: 0

Personalized bacteriophage therapy for chronic biliary tract Pseudomonas aeruginosa infections 慢性胆道铜绿假单胞菌感染的个性化噬菌体治疗

hLife

Pub Date : 2025-06-01 DOI: 10.1016/j.hlife.2025.03.004

Na Li , Linlin Li , Bo He , Dandan Li , Wenting Jin , Yuan Wu , Beidi Zhu , Mengjun Cheng , Nannan Wu , Demeng Tan , Jue Pan , Chunmei Zhou , Rong Bao , Hao Wu , Wen Zhang , Ming Li , Zhuojun Zhong , Jiazhen Liu , Jianglin Liao , Tongyu Zhu , Shuai Le

Biliary tract infections (BTIs) present a significant therapeutic challenge, particularly in the face of increasing antimicrobial resistance. Bacteriophages, viruses that target and destroy bacteria, offer the potential for treating severe bacterial infections, although their use in BTIs has been limited. We describe an 88-year-old female with a complex and recurrent BTI caused by multiple bacteria, including multidrug-resistant Pseudomonas aeruginosa. Despite treatment with various antibiotics and percutaneous transhepatic cholangiodrainage (PTCD), her condition did not improve. As a final measure, we implemented personalized phage therapy in combination with antibiotics. An initial 9-day antibiotic treatment combined with a P. aeruginosa phage cocktail administered via PTCD fluid resulted in significant symptom relief. However, phage-resistant pathogens emerged, exhibiting resistance to all 100 double-stranded DNA (dsDNA) phages in our library due to genetic mutations affecting lipopolysaccharides biosynthesis. A second round of therapy with a double-stranded RNA (dsRNA) phage, phiYY, which targets O-antigen deficient mutants, was subsequently administered. Although complete eradication of P. aeruginosa was not achieved, the patient's clinical symptoms were markedly improved. This case demonstrated the safety and efficacy of phage therapy in the treatment of BTIs and showcased the feasibility of employing dsRNA phages to combat the emergence of O-antigen-deficient bacterial mutants. However, it also underscores the considerable challenges in completely eradicating persistent P. aeruginosa infections, which may be attributed to bacterial heterogeneity, biofilm formation, and phage-resistant genetic mutations.

胆道感染（BTIs）提出了一个重大的治疗挑战，特别是面对日益增加的抗菌素耐药性。噬菌体是一种靶向并摧毁细菌的病毒，它为治疗严重的细菌感染提供了潜力，尽管它们在bti中的应用有限。我们描述了一位88岁的女性，她患有复杂的复发性BTI，由多种细菌引起，包括耐多药铜绿假单胞菌。尽管经各种抗生素和经皮肝胆管引流（PTCD）治疗，她的病情没有改善。作为最后的措施，我们实施个性化噬菌体治疗联合抗生素。最初的9天抗生素治疗结合pptcd液体给予铜绿假单胞菌噬菌体鸡尾酒治疗，显著缓解了症状。然而，噬菌体抗性病原体出现了，由于影响脂多糖生物合成的基因突变，它们对我们文库中所有100种双链DNA （dsDNA）噬菌体都具有抗性。随后使用针对o抗原缺陷突变体的双链RNA （dsRNA）噬菌体phiYY进行第二轮治疗。虽然铜绿假单胞菌没有完全根除，但患者的临床症状明显改善。该病例证明了噬菌体治疗BTIs的安全性和有效性，并展示了利用dsRNA噬菌体对抗o抗原缺陷细菌突变体出现的可行性。然而，它也强调了完全根除持续性铜绿假单胞菌感染的相当大的挑战，这可能归因于细菌异质性，生物膜形成和噬菌体抗性基因突变。

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