Microbial pathogenesis最新文献_第7页

The first report of submandibular lymph node infection with Flavobacterium ceti in a horse and its complete genome sequence 首次报道一匹马的颌下淋巴结感染黄杆菌 ceti 及其完整基因组序列。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-31 DOI: 10.1016/j.micpath.2024.107096

Seung-Ho Ryu , Beomsoon Jang , Byung-Sun Kim , Kun Taek Park

This is the first report describing the isolation and genome sequence of Flavobacterium ceti (F. ceti IJFC025) from a draining submandibular lymph node abscess in a 6-year-old mixed-breed mare in Korea. Since F. ceti is not a usual infectious pathogen that causes equine health problems, this study presents the complete genome sequence of F. ceti isolated from a submandibular lymph node abscess sample in Jeju, South Korea, in 2022. The entire genome sequence of F. ceti IJFC025 consisted of a 3,144,426-bp chromosome with 35.6 % G + C content. Gene prediction revealed that this strain possesses 2909 coding sequences (CDSs), 74 tRNAs, and five rRNAs. Average nucleotide identity analysis of the whole-genome sequence revealed 98.6 %–98.8 % nucleotide identity between F. ceti IJFC025 and F. ceti CECT7184, which was previously isolated from beaked whales. PathogenFinder revealed four different virulence genes in the genome that could potentially cause infections in horses. F. ceti CECT7184 contained genes encoding propionyl-CoA carboxylase, 3-oxoacid CoA-transferase A subunit, and the translation initiation factor IF-1, whereas F. ceti IJFC025 does not. Instead, F. ceti IJFC025 harbors genes encoding deoxyhypusine synthase, whereas F. ceti CECT7184 does not. Antimicrobial susceptibility tests revealed that F. ceti IJFC025 is a multidrug-resistant strain that is resistant to gentamicin, ceftazidime, nalidixic acid, ciprofloxacin, and colistin. However, no resistance genes were detected in the whole-genome sequence. Because of the similarity of the clinical signs with those of strangles, this pathogen needs to be included in the differential diagnosis of submandibular lymphadenopathy in horses.

这是首次报道从韩国一匹 6 岁混血母马的颌下淋巴结引流脓肿中分离出 F. ceti（F. ceti IJFC025）并对其进行基因组测序。由于 F. ceti 并非导致马匹健康问题的常见感染性病原体，本研究展示了 2022 年从韩国济州岛颌下淋巴结脓肿样本中分离出的 F. ceti 的完整基因组序列。F. ceti IJFC025的全基因组序列由3,144,426-bp染色体组成，G+C含量为35.6%。基因预测显示，该菌株拥有 2,909 个编码序列（CDS）、74 个 tRNA 和 5 个 rRNA。全基因组序列的平均核苷酸同一性分析表明，F. ceti IJFC025与之前从喙鲸体内分离出的F. ceti CECT7184的核苷酸同一性在98.6%到98.8%之间。PathogenFinder 在基因组中发现了四个不同的毒力基因，这些基因可能会导致马匹感染。F. ceti CECT7184含有编码丙酰-CoA羧化酶、3-氧代酸CoA-转移酶A亚基和翻译起始因子IF-1的基因，而F. ceti IJFC025则没有。相反，F. ceti IJFC025 含有编码脱氧羽扇豆碱合成酶的基因，而 F. ceti CECT7184 则没有。抗菌药敏感性测试表明，F. ceti IJFC025 是一种耐多种药物的菌株，对庆大霉素、头孢唑肟、萘啶酸、环丙沙星和可乐定耐药。不过，在全基因组序列中没有检测到耐药基因。由于该病原体的临床症状与绞股蓝相似，因此需要将其纳入马下颌淋巴结病的鉴别诊断中。

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引用次数: 0

Isolation and characterization of a novel S-gene mutation porcine deltacoronavirus with high pathogenicity from diarrhea piglet in Zhejiang Province, China, 2022 中国浙江省 2022 年从腹泻仔猪中分离并鉴定出具有高致病性的新型 S 基因突变猪三角冠状病毒。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-30 DOI: 10.1016/j.micpath.2024.107095

Xiangwen Xu , Jing Sun , Huihua Zheng , Xiaoxu Du , Yutao Wang , Jiongze Cheng , Yijia Liu , Jiale Ying , Yulin Zhao , Ziqi Wang , Junfang Yan , Xing Duan , Yongchun Yang , Zhihui Ye , Dongbo Sun , Houhui Song , Mingjun Su

Porcine deltacoronavirus (PDCoV) is a coronavirus that causes diarrhea in suckling piglets and has the potential for cross-species transmission. Monitoring PDCoV evolution and identifying potential vaccine candidates are crucial due to its high mutation rates in pig populations. In this study, a Chinese PDCoV strain named ZD2022 was successfully isolated from diarrhea piglets in Zhejiang province, followed by genetic evolutionary analysis, assessment of S proteins’ biological functions, in vitro cellular adaptation analysis and pathogenicity evaluation. Phylogenetic analyses placed the PDCoV ZD2022 strain within the Southeast Asia Lineage. Sequence analysis revealed 23 mutations in the S protein of ZD2022 compared to most of other Chinese PDCoV strains, including 8 unique mutations (T529I, L579F, Q614H, V709G, S959L, P1010S, V1016F, A1068V). In addition, bioinformatic predictions indicated these mutations impact the hydrophilicity/hydrophobicity, antigenic epitopes and N-glycosylation sites of the ZD2022 S protein. The virus growth curve of ZD2022 showed good cellular adaptation, with peak viral titers of 8.92 ± 0.31 Log₁₀ TCID₅₀/mL in ST cells. Furthermore, ZD2022 exhibited high virulence in suckling piglets, causing severe diarrhea in piglets at 60 h post-inoculation (hpi) and a mortality rate of 40 % (2/5) within 96 hpi. In summary, our findings indicate that the Chinese PDCoV strains continue to mutate, and the novel S gene mutation in strain ZD2022 offers strong cellular adaptation and high pathogenicity, making it a potential candidate strain for vaccine development.

猪 deltacoronavirus（PDCoV）是一种冠状病毒，可导致哺乳仔猪腹泻，并具有跨物种传播的潜力。由于 PDCoV 在猪群中的变异率很高，因此监测 PDCoV 的进化和确定潜在的候选疫苗至关重要。本研究从浙江省腹泻仔猪中成功分离出一株名为 ZD2022 的中国 PDCoV，并对其进行了遗传进化分析、S 蛋白生物功能评估、体外细胞适应性分析和致病性评估。系统进化分析将 PDCoV ZD2022 株归入东南亚系。序列分析发现，与大多数中国PDCoV毒株相比，ZD2022的S蛋白有23个突变，其中包括8个独特的突变（T529I、L579F、Q614H、V709G、S959L、P1010S、V1016F、A1068V）。此外，生物信息学预测表明，这些突变会影响 ZD2022 S 蛋白的亲水性/疏水性、抗原表位和 N-糖基化位点。ZD2022 的病毒生长曲线显示出良好的细胞适应性，在 ST 细胞中的病毒滴度峰值为 8.92±0.31 Log10 TCID50/mL。此外，ZD2022 在哺乳仔猪中表现出很强的毒力，在接种后 60 小时（hpi）会导致仔猪严重腹泻，96 小时内死亡率为 40%（2/5）。总之，我们的研究结果表明，中国的 PDCoV 株系仍在不断变异，ZD2022 株系中的新型 S 基因突变具有很强的细胞适应性和高致病性，使其成为疫苗开发的潜在候选株。

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引用次数: 0

Changes in the serum proteome profile of patients with neuroborreliosis, foresters, and patients treated according to ILADS method 神经源性疾病患者、森林守护者和按照 ILADS 方法治疗的患者血清蛋白质组的变化。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-30 DOI: 10.1016/j.micpath.2024.107094

Agnieszka Gęgotek , Elżbieta Skrzydlewska , Monika Groth , Piotr Czupryna , Anna Moniuszko-Malinowska

Objectives

The aim of study was to evaluate the changes in proteomic profile of human serum induced by the development of tick-borne neuroborreliosis (NB), before/after therapy, patients treated with prolonged multidrug therapy according to ILADS (International Lyme and Associated Diseases Society), and foresters frequently exposed to tick bites.

Methods

A proteomics approach was used to analyze the expression of proteins in serum of patients and sex/age-matched healthy donors. The analysis was performed using SDS-PAGE/LC-MS/MS (Q-Exactive OrbiTrap mass spectrometer).

Results

Obtained results indicated changes in the serum proteome of patients with NB putting attention to the proteins involved mainly in calcium transport/metabolism and signaling molecules that differ patients before and after classic therapy. Moreover, ILADS treated patients have different protein distribution than patients from other groups, what is the consequence of prolonged antibiotic therapy. In the case of foresters, the most important result is the increased β-secretase level.

Conclusions

Obtained results may contribute to a better understanding of the mechanism of the development of tick-borne diseases, as well as will allow create new opportunities for its rapid and more effective therapy. However, further studies, on larger patients groups, are needed to apply them in clinical practice.

研究目的本研究旨在评估蜱媒神经性包虫病（NB）发生、治疗前后、根据国际莱姆及相关疾病协会（ILADS）长期接受多种药物治疗的患者以及经常接触蜱虫叮咬的林业人员血清蛋白质组谱的变化：方法：采用蛋白质组学方法分析患者和性别/年龄匹配的健康供体血清中蛋白质的表达。分析采用 SDS-PAGE/LC-MS/MS（Q-Exactive OrbiTrap 质谱仪）进行：结果：研究结果表明，NB 患者血清蛋白质组发生了变化，主要涉及钙转运/代谢和信号分子的蛋白质在经典疗法前后有所不同。此外，ILADS 治疗患者的蛋白质分布与其他组别患者不同，这是长期抗生素治疗的结果。在森林人中，最重要的结果是β-分泌酶水平升高：获得的结果可能有助于更好地了解蜱传疾病的发病机制，并为快速、更有效地治疗蜱传疾病创造新的机会。不过，要将其应用于临床实践，还需要在更大的患者群体中开展进一步研究。

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引用次数: 0

Molecular patterns of microbial and metabolic interactions in septic patients with persistent lymphopenia 患有持续淋巴细胞减少症的脓毒症患者体内微生物与新陈代谢相互作用的分子模式。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-30 DOI: 10.1016/j.micpath.2024.107093

Juanjuan Jing , Xiaonan Li , Shanshan Liu , Jiawen Yu , Kaixuan Wang , Yi Li , Jia Wang , Xianyao Wan

Background

Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear.

Methods

This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n = 21) and non-persistent lymphopenia (<3d) (n = 15).

Results

The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3⁺T/LY, CD3⁺T cells, CD3⁺CD4⁺T cells, CD3⁺CD8⁺T cells, Th1 cells, Th2 cells, CD45RA ⁺ Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia.

Conclusion

In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.

背景：持续性淋巴细胞减少症可被视为脓毒症患者获得性免疫功能障碍的一个重要指标。淋巴细胞减少症脓毒症患者的特异性免疫因子是否会发生变化以及与肠道微生物群和代谢物的相关性仍不清楚：本项单中心前瞻性观察对36例持续性（≥3d）（n=21）和非持续性淋巴细胞减少症患者的血液样本进行了淋巴细胞亚组分析，并对粪便样本进行了16S rRNA基因扩增子测序和非靶向代谢组学分析（结果：持续性淋巴细胞减少症患者的淋巴细胞比非持续性淋巴细胞减少症患者的淋巴细胞高，而非持续性淋巴细胞减少症患者的淋巴细胞比持续性淋巴细胞减少症患者的淋巴细胞高：持续性淋巴细胞减少症患者的28d死亡率和90d死亡率均较高，而CD3+T/LY、CD3+T细胞、CD3+CD4+T细胞、CD3+CD8+T细胞、Th1细胞、Th2细胞、CD45RA+Treg细胞均显著降低。16S rRNA结果显示，葡萄球菌、肽链球菌、布氏球菌、白念珠菌在持续性淋巴细胞减少症中明显富集。代谢组学分析表明，持续性淋巴细胞减少症中α-酮异戊酸增加，7-DHCA、α-MCA、β-MCA、HCA、LCA-3S、CA、UCA和柠檬酸减少：结论：在持续性淋巴细胞减少症败血症患者宿主受体与肠道微生物群相互作用的过程中，肠道微生物群多样性和胆汁酸代谢产物显著减少。这会影响肠道免疫细胞的各种炎症通路，导致机体免疫功能紊乱，这可能是死亡的主要原因之一。

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引用次数: 0

Phage therapy: A targeted approach to overcoming antibiotic resistance 噬菌体疗法：克服抗生素耐药性的靶向方法。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-29 DOI: 10.1016/j.micpath.2024.107088

David B. Olawade , Oluwaseun Fapohunda , Eghosasere Egbon , Oladipo A. Ebiesuwa , Sunday Oluwadamilola Usman , Alaba O. Faronbi , Sandra Chinaza Fidelis

The rise of antibiotic-resistant bacterial infections has become a significant global health threat, necessitating the need for alternative therapeutic strategies. The use of bacteriophages—viruses that particularly infect and lyse bacteria—in phage therapy has resurfaced as a potentially effective substitute for conventional antibiotics. This narrative review aims to explore the mechanisms, applications, challenges, and prospects of phage therapy in combating antibiotic-resistant infections. A thorough analysis of the literature was carried out by exploring online databases, such as Google Scholar, PubMed, Scopus, and Web of Science. The search focused on peer-reviewed articles, clinical trials, and authoritative reports published in the last 10 years. The review synthesized findings from studies on phage mechanisms, therapeutic applications, regulatory challenges, and advances in phage engineering. Phage therapy demonstrates several advantages over antibiotics, including high specificity for target bacteria, the ability to penetrate biofilms, and a lower propensity for resistance development. However, significant challenges remain, such as regulatory and production hurdles, the potential for phage resistance, and interactions with the host immune system. Advances in genetic engineering have enhanced the therapeutic potential of phages, and personalized phage therapy is emerging as a viable approach for tailored treatments. Phage therapy holds significant promise as an alternative to antibiotics, particularly in the fight against antibiotic-resistant bacteria. While challenges persist, ongoing research, technological advancements, and collaborative efforts are crucial for integrating phage therapy into mainstream clinical practice, potentially revolutionizing the treatment of bacterial infections and addressing the global antibiotic resistance crisis.

抗生素耐药细菌感染的增加已成为全球健康的重大威胁，因此需要替代治疗策略。在噬菌体疗法中使用噬菌体--特别是能感染和裂解细菌的病毒--作为传统抗生素的潜在有效替代品再次兴起。这篇叙述性综述旨在探讨噬菌体疗法在对抗抗生素耐药性感染方面的机制、应用、挑战和前景。通过搜索 Google Scholar、PubMed、Scopus 和 Web of Science 等在线数据库，对文献进行了全面分析。搜索的重点是过去 10 年发表的同行评议文章、临床试验和权威报告。该综述综合了有关噬菌体机制、治疗应用、监管挑战和噬菌体工程进展的研究结果。与抗生素相比，噬菌体疗法具有多项优势，包括对目标细菌的高度特异性、穿透生物膜的能力以及较低的抗药性产生倾向。然而，噬菌体疗法仍面临重大挑战，如监管和生产障碍、噬菌体产生抗药性的可能性以及与宿主免疫系统的相互作用。基因工程的进步增强了噬菌体的治疗潜力，个性化噬菌体疗法正在成为一种量身定制治疗的可行方法。噬菌体疗法有望成为抗生素的替代疗法，尤其是在抗击耐抗生素细菌方面。虽然挑战依然存在，但持续的研究、技术进步和合作努力对于将噬菌体疗法纳入主流临床实践至关重要，这有可能彻底改变细菌感染的治疗方法，并解决全球抗生素耐药性危机。

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引用次数: 0

The oncomicrobiome: New insights into microorganisms in cancer 微生物组：对癌症微生物的新认识。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-29 DOI: 10.1016/j.micpath.2024.107091

Yingying Ma , Tao Chen , Tingting Sun , Dilinuer Dilimulati , Yonghong Xiao

The discoveries of the oncomicrobiome (intratumoral microbiome) and oncomicrobiota (intratumoral microbiota) represent significant advances in tumor research and have rapidly become of key interest to the field. Within tumors, microorganisms such as bacteria, fungi, viruses, and archaea form the oncomicrobiota and are primarily found within tumor cells, immunocytes, and the intercellular matrix. The oncomicrobiome exhibits marked heterogeneity and is associated with tumor initiation, progression, metastasis, and treatment response. Interactions between the oncomicrobiome and the immune system can modulate host antitumor immunity, influencing the efficacy of immunotherapies. Oncomicrobiome research also faces numerous challenges, including overcoming methodological issues such as low target abundance, susceptibility to contamination, and biases in sample handling and analysis methods across different studies. Furthermore, studies of the oncomicrobiome may be confounded by baseline differences in microbiomes among populations driven by both environmental and genetic factors. Most studies to date have revealed associations between the oncomicrobiome and tumors, but very few have established mechanistic links between the two. This review introduces the relevant concepts, detection methods, sources, and characteristics of the oncomicrobiome. We then describe the composition of the oncomicrobiome in common tumors and its role in shaping the tumor microenvironment. We also discuss the current problems and challenges to be overcome in this rapidly progressing field.

肿瘤微生物组（瘤内微生物组）和瘤上微生物群（瘤内微生物群）的发现代表了肿瘤研究的重大进展，并迅速成为该领域关注的焦点。在肿瘤内，细菌、真菌、病毒和古细菌等微生物构成了肿瘤微生物群，主要存在于肿瘤细胞、免疫细胞和细胞间质中。肿瘤微生物群具有明显的异质性，与肿瘤的发生、发展、转移和治疗反应有关。肿瘤微生物组与免疫系统之间的相互作用可调节宿主的抗肿瘤免疫力，从而影响免疫疗法的疗效。肿瘤微生物组研究也面临诸多挑战，包括克服方法问题，如目标丰度低、易受污染以及不同研究中样本处理和分析方法的偏差。此外，受环境和遗传因素的影响，不同人群的微生物组存在基线差异，这可能会干扰对微生物组的研究。迄今为止，大多数研究都揭示了体内微生物组与肿瘤之间的关联，但很少有研究建立了两者之间的机理联系。本综述介绍了本微生物组的相关概念、检测方法、来源和特征。然后，我们将介绍常见肿瘤中内微生物组的组成及其在塑造肿瘤微环境中的作用。我们还讨论了这一进展迅速的领域目前存在的问题和需要克服的挑战。

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引用次数: 0

The origin and evolution of European eel rhabdovirus dominant genotype 欧洲鳗鱼横纹肌病毒优势基因型的起源和演变。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-29 DOI: 10.1016/j.micpath.2024.107054

Chao Kong , Sheng-Wen Li , Jian Su , Li-Guo Zang , Mei He , Nai-Zheng Ding , Cheng-Qiang He

The Eel Virus European X (EVEX) is a significant pathogen contributing to the decline of eel populations. As an important evolutionary driving force, it is crucial to understand whether homologous recombination (HR)occurs between EVEXs for revealing the evolutionary patterns of the virus. This study indicates that HR may enhance genetic diversity and accelerate the evolution and spread of EVEX. Phylogenetic analysis reveals that the current popular EVEX is primarily composed of a dominant recombinant genotype. Further investigation suggests that recombination events, which likely occurred approximately 54 years ago, may alter codon preferences, highlighting the adaptive advantages this provides and enhancing the virus's ability to infect its eel host. The emergence of this advantageous genotype may be driven by environmental selection pressures, consistent with natural selection principles. In summary, our findings suggest that HR might plays an important role in EVEX evolution, facilitating its adaptation to changing environmental conditions.

欧洲鳗鱼病毒X（EVEX）是导致鳗鱼种群数量下降的重要病原体。作为一种重要的进化驱动力，了解EVEX之间是否发生同源重组（HR）对于揭示病毒的进化模式至关重要。本研究表明，同源重组可能会提高遗传多样性，加速EVEX的进化和传播。系统发生学分析表明，目前流行的EVEX主要由显性重组基因型组成。进一步的研究表明，重组事件可能发生在大约 54 年前，重组事件可能改变了密码子的偏好，从而突出了病毒的适应优势，并增强了病毒感染鳗鱼宿主的能力。这种优势基因型的出现可能是由环境选择压力驱动的，符合自然选择原则。总之，我们的研究结果表明，HR 可能在 EVEX 的进化过程中发挥了重要作用，促进其适应不断变化的环境条件。

引用次数: 0

Inhibition of Candida albicans virulence by moscatin from Dendrobium nobile lindl. 金钗石斛中的莫斯卡丁对白色念珠菌毒力的抑制作用

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-29 DOI: 10.1016/j.micpath.2024.107089

Bing Wang , Huihui Tan , Xiuyun Sun , Zizi Lin , Xiayu Chen , Hongguang Han , Mingfang Wang , Zijie Wang , Xiangxiu Chen , Yinyue Deng , Shihao Song

Candida albicans infection poses a significant global health threat. It is imperative to exploit new antifungal agents against C. albicans infections without leading to drug resistance, so that these potential agents can complement or combine with current medications to effectively treat diseases caused by C. albicans. We screened moscatin, and assessed the inhibitory effectiveness against C. albicans SC5314 on hyphae production and biofilm formation. It was revealed that moscatin exhibited significant effects on morphological transition and biofilm formation in C. albicans SC5314. It also lowered the pathogenicity of C. albicans SC5314 in a concentration-dependent way in both A549 cells and mice fungal infection models, but had no cytotoxicity to A549 cells. In addition, moscatin attenuated the virulence of clinical fluconazole-resistant C. albicans and exhibited synergistic activity with fluconazole. It could also restore the composition and richness of the intestinal microbiota in mice infected by C. albicans. These findings indicate that these moscatin has great potential to be developed as a new therapeutic drug against C. albicans infection.

白念珠菌感染对全球健康构成重大威胁。当务之急是在不导致耐药性的前提下开发新的抗真菌药物，使这些潜在药物能够补充或结合现有药物，有效治疗由白念珠菌引起的疾病。我们筛选了moscatin，并评估了其对白僵菌SC53145菌丝产生和生物膜形成的抑制效果。结果表明，moscatin 对白僵菌 SC53145 的形态转变和生物膜形成有显著影响。它还以浓度依赖的方式降低了白僵菌 SC53145 在 A549 细胞和小鼠真菌感染模型中的致病性，但对 A549 细胞没有细胞毒性。此外，moscatin 还能减弱对氟康唑耐药的临床白僵菌的毒力，并与氟康唑具有协同活性。它还能恢复被白僵菌感染的小鼠肠道微生物群的组成和丰富度。这些研究结果表明，moscatin 具有很大的开发潜力，可作为治疗白僵菌感染的新药。

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引用次数: 0

Anti-quorum sensing and anti-biofilm activities of Pasteurella multocida strains 多杀性巴氏杆菌菌株的抗菌群感应和抗生物膜活性。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-29 DOI: 10.1016/j.micpath.2024.107085

Arul Dhayalan , Awadhesh Prajapati , Revanaiah Yogisharadhya , Mohammed Mudassar Chanda , Sathish Bhadravati Shivachandra

A total of 52 Pasteurella multocida strains of capsular serogroups (A, B and D) were screened for anti-quorum sensing activity against Chromobacterium violaceum. Of which, 12 strains of serogroups A were found to possess anti-quorum sensing activity. Inhibition activity was highest for strain NIVEDIPm9 and lowest for strain NIVEDIPm30 based on zone of pigment inhibition. Further, cell free extract of NIVEDIPm9 strain showed highest anti-biofilm activity in reference E. coli strain and concentration dependent degradation activity of C6-AHL molecule. In whole genome sequence annotation of NIVEDIPm9 strain predicted the presence of four metallo-β-lactamases (MBL) fold metallo-hydrolase proteins. In docking studies, MBL1 and MBL3 proteins showed high binding affinity with autoinduce signalling molecules AHL compound of OH-C10, binding energy value were −6.3 and −6.2 kcal/mol. Interaction study of VAF and quorum sensing molecules showed that OmpA and HgbA proteins were stimulated by all the ten molecules (C4-AHLs, C6-AHLs, C10-AHLs, C14-AHLs, 3-oxo-C10-AHLs, 3OH-C10-HSL, C8-HSL, C10-HSL, C12-HSL, C14-HSL), while toxA gene was stimulated by OH-C10-AHL molecule, sodC gene was stimulated by none. In conclusion, we described the anti-quorum sensing activities of diverse P. multocida strains causing Pasteurellosis in livestock.

研究人员筛选了 52 株多杀性巴氏杆菌菌株（A、B 和 D 血清群），以检测它们是否具有抗初乳杆菌（Chromobacterium violaceum）的法定人数感应活性。结果发现，其中 12 株 A 血清群菌株具有抗法定人数感应活性。根据色素抑制区，NIVEDIPm9 菌株的抑制活性最高，NIVEDIPm30 菌株的抑制活性最低。此外，NIVEDIPm9 菌株的无细胞提取物显示出对参考大肠杆菌菌株最高的抗生物膜活性，以及与浓度相关的 C6-AHL 分子降解活性。在 NIVEDIPm9 菌株的全基因组序列注释中，预测出存在四种金属-β-内酰胺酶（MBL）折叠金属-水解酶蛋白。在对接研究中，MBL1 和 MBL3 蛋白与 OH-C10 的自诱导信号分子 AHL 化合物表现出很高的结合亲和力，结合能值分别为 -6.3 和 -6.2 kcal/mol。VAF与法定量传感分子的相互作用研究表明，OmpA和HgbA蛋白受到所有10种分子（C4-AHLs、C6-AHLs、C10-AHLs、C14-AHLs、3-oxo-C10-AHLs、3OH-C10-HSL、C8-HSL、C10-HSL、C12-HSL、C14-HSL）的刺激，而toxA基因受到OH-C10-AHL分子的刺激，sodC基因不受任何刺激。总之，我们描述了引起家畜巴氏杆菌病的不同多核荚膜杆菌菌株的抗菌群感应活性。

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引用次数: 0

A silver lining in MRSA treatment: The synergistic action of poloxamer-stabilized silver nanoparticles and methicillin against antimicrobial resistance 治疗 MRSA 的一线希望：聚氧乙烯稳定银纳米粒子和甲氧西林对抗菌药耐药性的协同作用。

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2024-10-29 DOI: 10.1016/j.micpath.2024.107087

Nijil S, Sinchana G Bhat, Anushree Kedla, Mahima Rachel Thomas, Sudarshan Kini

Background

Increasing antibiotic resistance in bacterial infections, including drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), necessitates innovative therapeutic solutions. Silver nanoparticles are promising for combating infections, but toxicity concerns emphasize the importance of factors like dosage, size, shape, and surface chemistry. Hence, exploring poloxamer as a stabilizing agent to reduce its toxicity and enhance the antibacterial effect on MRSA is investigated.

Methods

Silver nanoparticles stabilized with poloxamer (AgNPs@Pol) were synthesized through the chemical reduction method and characterized using UV–visible spectrophotometer, HR-TEM, DLS, and Zeta potential measurements. Subsequently, the antibacterial activity of AgNPs@Pol alone and in combination with methicillin against MRSA and methicillin-susceptible S. aureus (MSSA) was evaluated using the broth microdilution method.

Results

AgNPs@Pol showed significant efficacy against MRSA and MSSA, achieving a 100 % reduction in colony-forming units (CFU) at 9.7 μg/ml. The minimum inhibitory concentration (MIC) against MRSA and MSSA was 8.6 μg/ml and 4.3 μg/ml, respectively. A synergistic effect was observed when AgNPs@Pol was combined with methicillin. Treatment with AgNPs@Pol increased reactive oxygen species (ROS) production in both strains, contributing to its antibacterial activity. Real-time qPCR analysis indicated the downregulation of genes involved in antimicrobial resistance and cell adhesion in both strains. Further, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated low cytotoxicity for AgNPs@Pol against MCF-7, MG-63, and NIH-3T3 cell lines.

Conclusion

The developed AgNPs@Pol demonstrated extensive colloidal stability, potent antibacterial activity and synergistic effect with methicillin against MRSA and MSSA. Further studies in primary cells and in vivo models may validate its potential for clinical applications.

背景：细菌感染中的抗生素耐药性（包括耐甲氧西林金黄色葡萄球菌（MRSA）等耐药菌株）不断增加，因此需要创新的治疗方案。银纳米粒子在抗感染方面前景广阔，但毒性问题强调了剂量、大小、形状和表面化学等因素的重要性。因此，研究人员探索将聚氧乙烯作为稳定剂，以降低其毒性并增强对 MRSA 的抗菌效果：方法：通过化学还原法合成了用聚氧乙烯稳定的银纳米粒子（AgNPs@Pol），并使用紫外可见分光光度计、HR-TEM、DLS 和 Zeta 电位测量法对其进行了表征。随后，采用肉汤微稀释法评估了 AgNPs@Pol 单独或与甲氧西林复配对 MRSA 和甲氧西林敏感金黄色葡萄球菌（MSSA）的抗菌活性：结果：AgNPs@Pol 对 MRSA 和 MSSA 有显著疗效，在 9.7 μg/ml 的浓度下，菌落形成单位（CFU）减少了 100%。对 MRSA 和 MSSA 的最小抑菌浓度（MIC）分别为 8.6 μg/ml 和 4.3 μg/ml。当 AgNPs@Pol 与甲氧西林结合使用时，观察到了协同效应。用 AgNPs@Pol 处理两种菌株会增加活性氧（ROS）的产生，从而提高其抗菌活性。实时 qPCR 分析表明，这两种菌株中涉及抗菌药耐药性和细胞粘附性的基因都出现了下调。此外，3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑（MTT）试验表明，AgNPs@Pol 对 MCF-7、MG-63 和 NIH-3T3 细胞系的细胞毒性较低：结论：所开发的 AgNPs@Pol 对 MRSA 和 MSSA 具有广泛的胶体稳定性、强效抗菌活性以及与甲氧西林的协同作用。在原代细胞和体内模型中的进一步研究可能会验证其临床应用潜力。

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