Microbial pathogenesis最新文献_第4页

Bioprocess and genetic advances enhancing Beauveria bassiana biocontrol efficacy 提高球孢白僵菌生物防治效果的生物工艺和遗传研究进展。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-30 DOI: 10.1016/j.micpath.2025.108272

Prakash Kolanchi, Nandha Saminathan, Dineshkumar Selvaraj, Aravinthraju Krishnamoorthy, Kavin Palanivelu, Annamalai Aruchalam

Beauveria bassiana is a widely exploited entomopathogenic fungus that has emerged as a central component of ecologically sustainable pest management. Recent years have witnessed rapid progress across its biological understanding, technological development, and application potential. This review synthesizes contemporary advances spanning infection biology, secondary metabolite biosynthesis, strain development, bioprocess engineering, formulation science, and genetic improvement. At the molecular level, multi-omics studies have elucidated the coordinated regulation of surface adhesion, cuticular penetration, host immune modulation, dimorphic transitions, and toxin production, revealing gene networks that govern virulence, stress tolerance, and ecological adaptation. These insights have informed improved strategies for strain isolation and high-throughput phenotypic screening, enabling the selection of isolates with enhanced pathogenicity, environmental robustness, and endophytic competence. Parallel advances in solid-state and submerged fermentation, supported by agro-industrial substrates and data-driven optimization, have strengthened large-scale production of infective propagules with consistent quality. Such gains are further reinforced by modern formulation approaches, including oil-based dispersions, encapsulation systems, nanoemulsions, and seed-coating technologies, which collectively improve spore stability, persistence, and delivery under heterogeneous field conditions. More recently, CRISPR/Cas-based genome editing and pathway engineering have opened new avenues for precision enhancement of virulence traits, metabolic output, and abiotic stress resilience. Despite these achievements, the broader adoption of B. bassiana remains constrained by variable field performance, slower speed of action relative to chemical insecticides, strain-dependent efficacy, and regulatory and quality-control challenges. By integrating fundamental biology with technological innovation and practical limitations, this review provides a coherent framework for advancing B. bassiana from laboratory optimization to reliable field implementation, underscoring its promise as a next-generation, environmentally aligned biocontrol agent in modern agriculture.

球孢白僵菌是一种被广泛利用的昆虫病原真菌，已成为生态可持续虫害管理的核心组成部分。近年来，在对其生物学认识、技术开发和应用潜力方面取得了快速进展。本文综述了感染生物学、次生代谢物生物合成、菌株发育、生物工艺工程、配方科学和遗传改良等方面的最新进展。在分子水平上，多组学研究已经阐明了表面粘附、表皮渗透、宿主免疫调节、二态转变和毒素产生的协调调节，揭示了控制毒力、应激耐受性和生态适应的基因网络。这些见解为菌株分离和高通量表型筛选提供了改进的策略，使选择具有增强致病性，环境稳健性和内生能力的分离株成为可能。在农业工业基质和数据驱动优化的支持下，固态发酵和深层发酵的平行发展，加强了感染性繁殖体的大规模生产，并保持了一致的质量。现代配方方法进一步加强了这些成果，包括油基分散体、封装系统、纳米乳液和种子包衣技术，这些技术共同提高了孢子的稳定性、持久性和在异质野外条件下的传递能力。最近，基于CRISPR/ cas的基因组编辑和途径工程为精确增强毒力特性、代谢输出和非生物应激恢复能力开辟了新的途径。尽管取得了这些成就，但球孢白僵菌的广泛应用仍然受到田间性能变化、作用速度相对于化学杀虫剂较慢、菌株依赖的功效以及监管和质量控制方面的挑战的限制。通过将基础生物学与技术创新和实际限制相结合，本综述为推进球孢白僵菌从实验室优化到可靠的现场实施提供了一个连贯的框架，强调了它作为现代农业中下一代环保生物防治剂的前景。

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引用次数: 0

Exploring bacteriophages as potential tools for combating multi drug-resistant Klebsiella pneumoniae: Isolation, characterization, genomic insights, and in vitro evaluation 探索噬菌体作为对抗多重耐药肺炎克雷伯菌的潜在工具：分离、表征、基因组见解和体外评估

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-30 DOI: 10.1016/j.micpath.2025.108274

Rahma E. Ali , Amal S.M. Abo-Senna , Rasha A.S. El-Safty , Aliaa Aboulela

Bacteriophages are promising alternatives to antibiotics for combating multidrug-resistant (MDR) pathogens such as Klebsiella pneumoniae, a major cause of hospital-acquired infections. In this study, two K. pneumoniae-specific phages, vB_Kpn_RAH1 and vB_Kpn_RAH2, were isolated from sewage using an MDR clinical isolate (KP26) as the host. Their morphological, physicochemical, and genomic characteristics were analyzed. Both phages exhibited Siphovirus-like morphology, and the genome sizes of RAH1 and RAH2 were 46,784 bp and 59,380 bp, respectively. The phages were stable at 25–37 °C and pH 7–9 but were sensitive to high temperatures (80–90 °C), extreme pH, and prolonged UV exposure. Killing-curve assays confirmed strong bactericidal activity, with MOI 0.1 producing the most sustained bacterial reduction (90–97 %), while higher MOIs showed reduced long-term efficacy. The phage cocktail exhibited superior and prolonged inhibition of K. pneumoniae, outperforming RAH1 and RAH2 individually. One-step growth analysis revealed burst sizes of approximately 400 virions for RAH1 and 250 for RAH2. Host-range analysis indicated narrow specificity for both phages, whereas their cocktail displayed a broader lytic spectrum, lysing 9 of 15 clinical isolates. The absence of lysis in non-Klebsiella species emphasizes the high specificity of the phages, supporting a targeted therapeutic approach while minimizing unintended effects on the host microbiota. Genomic analysis confirmed that RAH1 and RAH2 are novel species lacking antimicrobial resistance and virulence genes. RAH2 is strictly lytic, whereas RAH1 is temperate. The strictly lytic nature and favorable genomic features of RAH2 support its potential as a candidate for therapeutic applications.

噬菌体是对抗肺炎克雷伯菌（医院获得性感染的主要原因）等多重耐药（MDR）病原体的有希望的抗生素替代品。本研究以MDR临床分离菌KP26为宿主，从污水中分离出两种肺炎克雷伯菌特异性噬菌体vB_Kpn_RAH1和vB_Kpn_RAH2。分析了它们的形态、理化和基因组特征。RAH1和RAH2的基因组大小分别为46,784 bp和59,380 bp。噬菌体在25-37°C和pH 7-9条件下稳定，但对高温（80-90°C）、极端pH和长时间紫外线照射敏感。杀伤曲线试验证实了较强的杀菌活性，MOI 0.1产生最持续的细菌减少（90 - 97%），而较高的MOI显示长期效果降低。噬菌体鸡尾酒对肺炎克雷伯菌的抑制效果优于RAH1和RAH2。一步生长分析显示，RAH1的爆发大小约为400个病毒粒子，RAH2的爆发大小约为250个。宿主范围分析表明，这两种噬菌体的特异性较窄，而它们的混合物显示出较宽的裂解谱，可裂解15种临床分离株中的9种。在非克雷伯氏菌物种中缺乏裂解强调了噬菌体的高特异性，支持靶向治疗方法，同时最大限度地减少对宿主微生物群的意外影响。基因组分析证实RAH1和RAH2是缺乏耐药和毒力基因的新种。RAH2是严格的裂解性，而RAH1是温和的。RAH2的严格裂解性质和有利的基因组特征支持其作为候选治疗应用的潜力。

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引用次数: 0

Recent advances in food preservation through antimicrobial carbon dots-based food packaging: Environmental sustainability and future trends 通过抗微生物碳点食品包装的食品保存的最新进展：环境可持续性和未来趋势

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-30 DOI: 10.1016/j.micpath.2025.108271

Ajahar Khan, Zohreh Riahi, Jun Tae Kim, Jong-Whan Rhim

Food contamination and health concerns due to foodborne pathogens have highlighted the need for novel antimicrobial agents to replace conventional packaging methods that use chemical preservatives. In terms of food safety, nanotechnology offers a variety of opportunities for the food sector, anticipating consumer demand for affordable, nutritious, and refined foods. In this regard, carbon dots have attracted significant attention as potential antimicrobial nanomaterials due to their structural versatility, ease of functionalization, and unique physicochemical, optical, non-toxic, biodegradable, and biocompatible properties. This review provides a systematic overview of the antimicrobial effects of carbon dots against various foodborne microorganisms, including bacteria, fungi, and viruses, which are necessary for evaluating sustainable food preservatives. Important concerns such as health, environmental, and safety issues, along with an overview of the targeting mechanisms between carbon dots and foodborne pathogens, are also discussed. Research advances in the development of carbon dots -integrated biopolymer-based antimicrobial food packaging systems are highlighted, focusing on their effectiveness in preserving the quality of fruits, vegetables, meat, dairy, and bakery products. Finally, challenges and potential future directions in the development of antimicrobial carbon dots are explored to provide a comprehensive understanding of the structure-activity linkages of carbon dots for microbial targeting.

由于食源性病原体引起的食品污染和健康问题突出表明需要新型抗菌剂来取代使用化学防腐剂的传统包装方法。在食品安全方面，纳米技术为食品部门提供了各种机会，预测消费者对负担得起的、有营养的和精制食品的需求。在这方面，碳点由于其结构通用性、易于功能化、独特的物理化学、光学、无毒、可生物降解和生物相容性等特性，作为潜在的抗菌纳米材料受到了极大的关注。本文综述了碳点对各种食源性微生物的抗菌作用，包括细菌、真菌和病毒，这是评价可持续食品防腐剂所必需的。重要的问题，如健康，环境和安全问题，以及碳点和食源性病原体之间的靶向机制的概述，也进行了讨论。重点介绍了碳点集成生物聚合物抗菌食品包装系统的研究进展，重点介绍了其在保持水果、蔬菜、肉类、乳制品和烘焙产品质量方面的有效性。最后，探讨了抗菌碳点发展的挑战和潜在的未来方向，以全面了解碳点的结构-活性联系，用于微生物靶向。

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引用次数: 0

Pathobionts in the microbiome: Drivers of disease and targets for treatment 微生物组中的病原体：疾病的驱动因素和治疗目标。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-27 DOI: 10.1016/j.micpath.2025.108268

Selvaraj Bharathi , Yolin Angel P.A. Soundara Rajan , Santhiyagu Prakash , Grasian Immanuel , Ramasamy Ramasubburayan

Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.

病原体是人类微生物群的共生居民，可以在特定的遗传或环境条件下过渡到致病状态。它们最近因对各种临床状况的影响而受到关注。本文综述了病原菌出现背后的关键因素，包括微生物生态失调、抗生素使用、饮食影响、免疫功能障碍和宿主遗传。它提供了与肠道、口腔和阴道微生物组相关的病原体的全面概述，突出了它们在疾病发病机制中的作用。一个重要的重点也放在病原体在免疫相关疾病的参与。此外，还重点介绍了当前和先进的治疗策略，如粪便微生物群移植、噬菌体治疗、益生菌和益生元，以及它们的优点和局限性。因此，结合微生物生态学、宿主免疫和治疗策略的综合观点概述了需要有针对性的、基于微生物组的干预措施来解决病原体的复杂行为。

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引用次数: 0

Bacillus-based probiotic supplementation improves serum antioxidant capacity and gut health in PEDV-infected piglets 添加以芽孢杆菌为基础的益生菌可提高pedv感染仔猪的血清抗氧化能力和肠道健康。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-26 DOI: 10.1016/j.micpath.2025.108266

Benhao Chen , Lixiao Duan , Yan Gao , John Kyaw Htoo , S. Maria Mendoza , Kangcheng Pan , Dongmei Zhang , Bo Jing , Yan Zeng , Hongli Ling , Xueqin Ni

This experiment investigated the effects of dietary supplementation with probiotic GutPlus® Virsorb (GV) on systemic antioxidant capacity and gut health in piglets infected with Porcine Epidemic Diarrhea Virus (PEDV). A total of 72 crossbred (Duroc × Landrace × Yorkshire) weaned piglets (21 days of age, 5.51 ± 0.44 kg) were randomly divided into: the CON1 group (negative control, basal diet), the CON2 group (positive control, basal diet), and the GV group (basal diet + 500 g/t GV). At 28 days of age, piglets in the CON2 and GV groups were challenged with oral inoculation with 40 mL PEDV (8.58 × 10⁸ copies/mL), whereas the CON1 group received an equivalent volume of DMEM medium. The experiment lasted until 60 days of age. Probiotic GV significantly enhanced systemic antioxidant capacity, as evidenced by elevated serum SOD activity and reduced MDA levels. Concurrently, GV effectively promoted gut health by alleviating ileal damage (improved villus architecture), reducing viral load and shedding, and reshaping the gut ecosystem. The latter included enriching beneficial bacteria (Lactobacillus, Limosilactobacillus, Phascolarctobacterium_A), reducing potentially harmful bacteria (Desulfovibrio_R), and increasing beneficial metabolites such as indolelactic acid and pinocembrin. In summary, probiotic GV supplementation alleviates PEDV infection in piglets by concurrently boosting host antioxidant defenses and restoring multiple facets of gut health. These findings support the potential of GV as a dietary strategy to enhance host resilience specifically against PEDV infection in weaned piglets.

本试验旨在研究饲粮中添加益生菌GutPlus®Virsorb （GV）对猪流行性腹泻病毒（PEDV）感染仔猪全身抗氧化能力和肠道健康的影响。试验选用72头21日龄、5.51±0.44 kg的杂交（杜×长×大）断奶仔猪，随机分为：CON1组（阴性对照，基础饲粮）、CON2组（阳性对照，基础饲粮）和GV组（基础饲粮+ 500g/t GV）。28日龄时，CON2组和GV组仔猪口服接种40 mL PEDV (8.58×108 copies/mL)， CON1组仔猪口服接种等量的DMEM培养基。试验持续至60日龄。益生菌GV显著增强全身抗氧化能力，血清SOD活性升高，MDA水平降低。同时，GV通过减轻回肠损伤（改善肠绒毛结构），减少病毒载量和脱落，重塑肠道生态系统，有效促进肠道健康。后者包括丰富有益细菌（Lactobacillus, Limosilactobacillus, phascolarctobacter_a），减少潜在有害细菌（Desulfovibrio_R），增加有益代谢物（如吲哚乳酸和匹诺松素）。综上所述，添加益生菌GV可通过同时增强宿主抗氧化防御和恢复肠道多个方面的健康来减轻仔猪PEDV感染。这些发现支持GV作为一种饲粮策略的潜力，以增强断奶仔猪对PEDV感染的宿主恢复力。

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引用次数: 0

Demonstration of antigenic site 3 in foot-and-mouth disease virus serotype A using neutralizing monoclonal antibody resistant mutants 利用中和性单克隆抗体抗性突变体证明甲型口蹄疫病毒抗原位点3。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-26 DOI: 10.1016/j.micpath.2025.108265

S. Shanmuganathan , Samriddhi Dubey , R. Hema Sayee , V. Bhanuprakash , Sivarama Krishna Gollapalli , Shreya Gopinath , Suresh Basagoudanavar , B.P. Sreenivasa , Jitendra Kumar Biswal , Madhusudan Hosamani

Foot-and-mouth disease (FMD) is a major viral infection in cloven-hoofed animals, causing significant economic losses worldwide. The etiological agent, Foot-and-Mouth Disease Virus (FMDV), exists in seven distinct serotypes (O, A, C, Asia 1, SAT 1–3), each with multiple subtypes. High mutation rate in FMDV often leads to the emergence of new antigenic variants, complicating vaccine development and control efforts. In this study, we focused on mapping antigenic determinants in the vaccine strain of FMDV serotype A. Using escape mutants generated with neutralizing monoclonal antibodies, we successfully mapped antigenic site 3. Furthermore, critical residues within antigenic site 1, (VP1 positions, 193/194 and 148) were identified in this serotype. Collectively, structural analyses reveal that antigenic sites across all FMDV serotypes are highly conserved, underscoring their potential as targets for broad-spectrum vaccine strategies.

口蹄疫是偶蹄类动物的一种主要病毒感染，在世界范围内造成重大经济损失。病原体口蹄疫病毒（FMDV）存在于7种不同的血清型（O、A、C、Asia 1、SAT 1-3）中，每种血清型都有多个亚型。口蹄疫病毒的高突变率常常导致新的抗原变异的出现，使疫苗开发和控制工作复杂化。在这项研究中，我们专注于定位FMDV血清型a疫苗株的抗原决定因子，使用中和单克隆抗体产生的逃逸突变体，我们成功定位了抗原位点3。此外，在该血清型中鉴定出抗原位点1的关键残基（VP1位置，193/194和148）。总体而言，结构分析表明，所有FMDV血清型的抗原位点高度保守，强调了它们作为广谱疫苗策略靶点的潜力。

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引用次数: 0

Neutrophils in Toxocara canis infection: Effector functions, immune evasion and crosstalk with type 2 immunity 犬弓形虫感染中的中性粒细胞：效应作用、免疫逃避和与2型免疫的串扰。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-26 DOI: 10.1016/j.micpath.2025.108267

Iman F. Abou-El-Naga

Toxocara canis is an important zoonotic parasite with significant clinical relevance to both veterinary and human health. While neutrophils have traditionally been associated with antimicrobial defense, their role as key modulators of immunity against helminths is increasingly recognized. Following infection with Toxocara canis, neutrophils are rapidly recruited through IL-17-mediated signaling cascades, triggered by tissue damage and parasite excretory-secretory products. Despite their several effector mechanisms, including degranulation, reactive oxygen species, and neutrophil extracellular traps, in vitro studies demonstrate that neutrophils are unable to kill Toxocara canis larvae, highlighting the parasite's sophisticated immune evasion strategies. However, in vivo, neutrophils exhibit striking plasticity. They adopt an N2 phenotype via the IL-17/IL-17RA axis. N2 neutrophils are characterized by production of key type 2 cytokines IL-4 and the amplifier cytokine IL-17. This axis plays a dual role; it reduces larval burden by promoting type 2 immune polarization via IL-4 and, simultaneously, amplifies pulmonary inflammation. The outcome of infection reflects a dynamic interplay among neutrophils, eosinophils, and macrophages. Neutrophil-derived IL-17 enhances eosinophil recruitment, whereas IL-4 drives macrophage polarization toward an M2 phenotype that sustains type 2 responses and encapsulates larvae together with other cells. While these interactions restrict larval migration, they also lead to tissue damage, illustrating the trade-off between protection and pathology. Overall, neutrophils in Toxocara canis infection are ineffective at killing the parasite directly, but are important as immunity regulators. Understanding their dual roles provides key insights into host-parasite interactions and can inform therapeutic approaches that strengthen antiparasitic defenses while mitigating immunopathology.

犬弓形虫是一种重要的人畜共患寄生虫，对兽医和人类健康都有重要的临床意义。虽然中性粒细胞传统上与抗菌防御有关，但它们作为对蠕虫免疫的关键调节剂的作用越来越被认识到。在感染犬弓形虫后，通过il -17介导的信号级联反应迅速募集中性粒细胞，这是由组织损伤和寄生虫排泄-分泌产物引发的。尽管它们具有多种效应机制，包括脱颗粒、活性氧和中性粒细胞细胞外陷阱，但体外研究表明，中性粒细胞无法杀死犬弓形虫幼虫，这突出了寄生虫复杂的免疫逃避策略。然而，在体内，中性粒细胞表现出惊人的可塑性。它们通过IL-17/IL-17RA轴呈N2表型。N2中性粒细胞的特征是产生关键的2型细胞因子IL-4和放大细胞因子IL-17。这个轴起着双重作用；它通过IL-4促进2型免疫极化来减轻幼虫负担，同时放大肺部炎症。感染的结果反映了中性粒细胞、嗜酸性粒细胞和巨噬细胞之间的动态相互作用。中性粒细胞来源的IL-17增强嗜酸性粒细胞募集，而IL-4驱动巨噬细胞向M2型极化，维持2型反应，并与其他细胞一起包裹幼虫。虽然这些相互作用限制了幼虫的迁移，但它们也导致组织损伤，说明了保护和病理之间的权衡。总的来说，中性粒细胞在犬弓形虫感染中不能直接杀死寄生虫，但作为免疫调节剂是重要的。了解它们的双重作用可以为宿主-寄生虫相互作用提供关键见解，并可以为加强抗寄生虫防御同时减轻免疫病理的治疗方法提供信息。

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引用次数: 0

Anti-virulence activity and immunomodulation of Oreoch-1 against enteroinvasive Escherichia coli infection Oreoch-1抗肠侵袭性大肠杆菌感染的毒力活性及免疫调节作用。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-26 DOI: 10.1016/j.micpath.2025.108253

Francesca Palma , Rosa Giugliano , Annalisa Chianese , Roberta Della Marca , Alessandra Monti , Nunzianna Doti , Carla Zannella , Massimiliano Galdiero , Anna De Filippis

Enteroinvasive Escherichia coli (EIEC) is a major causative agent of infectious diarrhea, associated with morbidity and mortality. The induction of host damage relies on specific virulence factors harbored by the large virulence plasmid pINV. Considering the recent outbreaks and the alarming emergence of drug-resistant EIEC strains, innovative interventional approaches are required. Anti-virulence interference appears promising as it targets bacterial virulence rather than viability, thereby posing a lower risk of inducing drug resistance. In this context, antimicrobial peptides (AMPs), usually short, cationic molecules, have emerged for their wide spectrum of activity. This study demonstrates the anti-virulence and immunomodulatory potential of Oreoch-1, a 23-mer cationic peptide derived from the Nile tilapia (Oreochromis niloticus), in an in vitro model of EIEC infection. We challenged EIEC ATCC 43983 strain with the peptide (3.125–25 μM) via broth microdilution method, assessing its slight activity in the range 6.25–12.5 μM. Then, we evaluated the ability of Oreoch-1 to interfere with the bacterial invasion process in the colon carcinoma cell line (Caco-2). We specifically assessed the ability of Oreoch-1 to modulate key virulence factors of EIEC, including ial, icsA, icsB, ipaB, ipaC, virB, and virF, as well as the expression of inflammatory cytokines such as IL-6, IL-8, IL-1β, TNF-α, and TGF-β. These factors play crucial roles in the infection process from both the bacterial and host perspectives. Given our promising results, Oreoch-1 may emerge as a potential novel antimicrobial peptide that addresses the concerning issue of widespread drug resistance.

肠侵入性大肠杆菌（EIEC）是感染性腹泻的主要病原体，与发病率和死亡率相关。宿主损伤的诱导依赖于大毒力质粒pINV所携带的特异性毒力因子。考虑到最近的疫情和令人震惊的耐药EIEC菌株的出现，需要创新的干预方法。抗毒力干扰似乎很有希望，因为它针对的是细菌的毒力而不是生存能力，从而降低了诱导耐药性的风险。在这种情况下，抗菌肽（AMPs），通常短，阳离子分子，已经出现了广泛的活性谱。本研究在EIEC感染的体外模型中证明了Oreoch-1的抗毒力和免疫调节潜力，Oreoch-1是一种从尼罗罗非鱼（Oreochromis niloticus）中提取的23个阳离子肽。用该肽（3.125 ~ 25 μM）对EIEC ATCC 43983菌株进行肉汤稀释，测定其在6.25 ~ 12.5 μM范围内的微活性。然后，我们评估了Oreoch-1对结肠癌细胞系（Caco-2）细菌侵袭过程的干扰能力。我们专门评估了Oreoch-1调节EIEC关键毒力因子的能力，包括ial、icsA、icsB、ipaB、ipaC、virB和virF，以及炎症细胞因子如IL-6、IL-8、IL-1β、TNF-α和TGF-β的表达。从细菌和宿主的角度来看，这些因素在感染过程中起着至关重要的作用。鉴于我们有希望的结果，Oreoch-1可能会成为一种潜在的新型抗菌肽，解决广泛的耐药性问题。

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引用次数: 0

Infection at the vascular front: A delicate balance between defense and pathology 血管前沿感染：防御与病理之间的微妙平衡。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-23 DOI: 10.1016/j.micpath.2025.108261

Jing Zhou , Decheng Wang , Bo Yan

The vascular system is far from a passive structure during infection; rather, it serves as a dynamic regulatory network that orchestrates the delicate balance between host defense and pathology. This review establishes a vessel-centered analytical framework to systematically elucidate the continuum of balance establishment, disruption, and restoration within infectious settings. During the defensive phase, the vasculature coordinates a tightly regulated response—moderately enhancing permeability, precisely recruiting immune cells, and initiating localized coagulation—to build an effective barrier against invading pathogens. However, when pathogen virulence exceeds host control or immune responses become dysregulated, this physiological defense machinery is subverted into a self-reinforcing pathological loop characterized by leakage, hypoxia, angiogenesis, and thrombosis. This vicious cycle amplifies tissue injury and disrupts vascular integrity. Successful infection control thus depends not only on pathogen clearance but also—more critically—on reversing this pathological cycle and restoring vascular function to reestablish homeostasis. Such vascular repair entails active resolution of inflammation, regeneration of the endothelial barrier, and normalization of aberrant vascular networks. Building on an integrated summary of the mechanisms underlying balance disruption, this review further explores emerging vascular-targeted therapeutic strategies aimed at redirecting vascular responses toward repair and homeostatic restoration. This integrative perspective provides a dynamic understanding of infection-associated vasculopathies and opens new avenues for therapies designed to reestablish host equilibrium.

在感染期间，血管系统远非被动结构；相反，它是一个动态的调节网络，协调宿主防御和病理之间的微妙平衡。本综述建立了一个以血管为中心的分析框架，以系统地阐明在感染环境中平衡的建立、破坏和恢复的连续体。在防御阶段，血管系统协调一个严格调节的反应——适度增强渗透性，精确地招募免疫细胞，并启动局部凝固——以建立一个有效的屏障来抵御入侵的病原体。然而，当病原体毒力超过宿主控制或免疫反应失调时，这种生理防御机制被破坏为以渗漏、缺氧、血管生成和血栓形成为特征的自我强化病理循环。这种恶性循环加剧了组织损伤，破坏了血管的完整性。因此，成功的感染控制不仅取决于病原体的清除，更重要的是，还取决于逆转这种病理循环和恢复血管功能以重建体内平衡。这种血管修复需要炎症的主动解决、内皮屏障的再生和异常血管网络的正常化。在综合总结平衡破坏机制的基础上，本综述进一步探讨了新兴的血管靶向治疗策略，旨在将血管反应重定向到修复和体内平衡恢复。这种综合视角提供了对感染相关血管病变的动态理解，并为旨在重建宿主平衡的治疗开辟了新的途径。

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引用次数: 0

Charge-dependent effects of nanoplastics on Helicobacter pylori virulence and gastric pathogenesis 纳米塑料对幽门螺杆菌毒力和胃发病机制的电荷依赖性影响。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2025-12-23 DOI: 10.1016/j.micpath.2025.108260

Wenke Wang , Xiaoying Chen , Shang Shi , Dina Johar , Fangshu Li , Boqing Li , Chunlei Ma , Yingzi Cui , Zhiqin Li , Ying Zhang

Nanoplastics (NPs) are emerging environmental contaminants whose surface charge governs their biological interactions. This study investigated how differentially charged NPs modulate Helicobacter pylori virulence and gastric pathogenesis. A chronic infection mouse model was used to evaluate co-exposure to H. pylori and positive (PS-NH₂), negative (PS-COOH), or neutral (PS) NPs. Gastric NPs accumulation and tissue injury were assessed by TEM and H&E staining. Oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), antioxidants such as superoxide dismutase (SOD) and glutathione (GSH), and cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the chemokine monocyte chemoattractant protein-1 (MCP-1), and the neutrophil enzyme myeloperoxidase (MPO), were quantified. The expression of virulence and adhesion genes, including cytotoxin-associated gene A (cagA), vacuolating cytotoxin A gene (vacA), blood group antigen-binding adhesin A gene (babA), and outer inflammatory protein A gene (oipA), was analyzed. Bacterial motility and biofilm formation were also evaluated. All NPs accumulated in gastric tissue and exacerbated injury, with severity following PS-NH₂ > PS-COOH > PS. Co-exposure elevated oxidative stress and inflammation while reducing antioxidant capacity. Virulence and adhesion genes were upregulated across NPs groups, with PS-NH₂ inducing early activation and PS-COOH causing sustained increases. PS-NH₂ NPs showed no significant effect on early bacterial motility but suppressed late-stage swimming. Biofilm formation was markedly increased, particularly with PS-NH₂ exposure. NPs exacerbate H. pylori–induced gastric injury in a surface charge–dependent manner by promoting bacterial virulence, oxidative stress, and inflammation. These findings provide new insights into host–pathogen interactions relevant to gastric disease.

纳米塑料（NPs）是一种新兴的环境污染物，其表面电荷决定了其生物相互作用。本研究探讨了不同电荷的NPs如何调节幽门螺杆菌的毒力和胃的发病机制。使用慢性感染小鼠模型来评估幽门螺杆菌和阳性（PS- nh2），阴性（PS- cooh）或中性（PS） NPs的共同暴露。透射电镜（TEM）和H&E染色观察胃内NPs积累情况和组织损伤情况。测定氧化应激标志物，包括活性氧（ROS）和丙二醛（MDA），抗氧化剂如超氧化物歧化酶（SOD）和谷胱甘肽（GSH），细胞因子白介素-6 （IL-6）和肿瘤坏死因子-α (TNF-α)，趋化因子单核细胞趋化蛋白-1 （MCP-1）和中性粒细胞酶髓过氧化物酶（MPO）。分析细胞毒素相关基因A （cagA）、空泡细胞毒素A基因（vacA）、血型抗原结合黏附素A基因（babA）、外炎症蛋白A基因（oipA）等毒力和黏附基因的表达情况。细菌运动和生物膜形成也进行了评估。所有NPs都在胃组织中积累并加重了损伤，在PS- nh2 > PS- cooh > PS之后更为严重。共暴露会增加氧化应激和炎症，同时降低抗氧化能力。NPs组毒力和粘附基因上调，PS-NH2诱导早期激活，PS-COOH持续升高。PS-NH2 NPs对细菌早期运动无显著影响，但对后期游泳有抑制作用。生物膜的形成明显增加，特别是暴露于PS-NH2时。NPs通过促进细菌毒力、氧化应激和炎症，以表面电荷依赖的方式加剧幽门螺杆菌诱导的胃损伤。这些发现为与胃病相关的宿主-病原体相互作用提供了新的见解。

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引用次数: 0