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Single-stranded DNA oligonucleotides containing CpG motifs are non-stimulatory in vitro but offer protection in vivo against Burkholderia pseudomallei. 含有 CpG 基序的单链 DNA 寡核苷酸在体外不具刺激性,但在体内却能对假丝酵母伯克霍尔德菌提供保护。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-18 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1458435
Andrew Scott, Benjamin Farrar, Tom Young, Joann Prior, Chad Stratilo, Leonie Unterholzner, Riccardo D'Elia

Therapies that modulate and appropriately direct the immune response are promising candidates for the treatment of infectious diseases. One such candidate therapeutic is DZ13, a short, synthetic, single-stranded DNA molecule. This molecule has enzymatic activity and can modulate the immune response by binding to and degrading the mRNA encoding a key immuno-regulatory molecule. Originally developed and entering clinical trials as an anti-cancer agent, DZ13 has also been evaluated as a treatment for viral infections, and has been shown to provide protection against infection with influenza virus in a mouse model of infection. In this work, we evaluated whether the immuno-modulatory properties of DZ13 could provide protection against the potential biothreat pathogen Burkholderia pseudomallei which causes the neglected tropical disease melioidosis. Treatment of mice infected with B. pseudomallei demonstrated that DZ13 did indeed provide excellent protection after only two post-exposure treatments. However, our data indicated that the enzymatic activity contained in DZ13 was not required for protection, with control oligonucleotide treatments lacking activity against the target mRNA equally as protective against B. pseudomallei. We have designed new sequences to study the mechanism of protection further. These novel sequences offer enhanced protection against infection, but are not directly anti-microbial and do not appear to be stimulating the immune system via TLR9 or other key innate immune sensors, despite containing CpG motifs. The molecular mechanism of these novel sequences remains to be elucidated, but the data highlights that these oligonucleotide-sensing pathways are attractive and relevant targets to modulate during bacterial and viral infections.

调节和适当引导免疫反应的疗法是治疗传染病的有前途的候选疗法。DZ13 就是这样一种候选疗法,它是一种合成的短单链 DNA 分子。这种分子具有酶活性,可以通过结合和降解编码关键免疫调节分子的 mRNA 来调节免疫反应。DZ13 最初是作为一种抗癌剂开发并进入临床试验阶段的,目前也已被评估为一种治疗病毒感染的药物,并已在小鼠感染模型中证明它能提供保护,防止感染流感病毒。在这项研究中,我们评估了 DZ13 的免疫调节特性是否能保护小鼠免受潜在的生物威胁病原体假马勒伯克霍尔德氏菌(Burkholderia pseudomallei)的感染。对感染假丝酵母菌的小鼠进行的处理表明,仅在暴露后进行两次处理后,DZ13 就能提供出色的保护作用。然而,我们的数据表明,DZ13 所含的酶活性并不是保护所必需的,对目标 mRNA 缺乏活性的对照寡核苷酸处理对假马雷菌同样具有保护作用。我们设计了新的序列来进一步研究保护机制。这些新型序列具有更强的抗感染保护能力,但并不直接具有抗微生物作用,而且尽管含有 CpG 基序,但似乎并没有通过 TLR9 或其他关键的先天性免疫传感器刺激免疫系统。这些新型序列的分子机制仍有待阐明,但这些数据突出表明,这些寡核苷酸传感途径是在细菌和病毒感染期间具有吸引力的相关调节靶标。
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引用次数: 0
Genomic and phenotypic characterization of a Clostridioides difficile strain of the epidemic ST37 type from China. 中国一株流行性 ST37 型艰难梭菌的基因组和表型特征。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-18 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1412408
Chunhui Li, Joshua Heuler, Duolong Zhu, Xiujuan Meng, Soumyadeep Chakraborty, Céline Harmanus, Shaohui Wang, Zhong Peng, Wiep Klaas Smits, Anhua Wu, Xingmin Sun

Clostridioides difficile strains of sequence type (ST) 37, primarily including PCR ribotype (RT) 017, are prevalent in mainland China. Our study aimed to compare the major virulence factors of an epidemic C. difficile isolate of ST37 type (Xy06) from China with the well-characterized C. difficile reference strains R20291 (RT027) and CD630E (ST54), as well as a Chinese ST54 strain (Xy07) isolated from the same hospital. The Xy06 genome was predicted to harbor two complete prophages and several transposon-like elements. Comparative analysis of PaLoc revealed a truncated tcdA gene, a functional tcdB gene, a functional tcdC gene, and well-conserved tcdR and tcdE genes. Phenotypic comparisons showed that Xy06 was a robust producer of TcdB, readily sporulated and germinated, and strongly bound to human gut epithelial cells. In a mouse model of C. difficile infection, Xy06 was more virulent than strains CD630E and Xy07 and was comparable to strain R20291 in virulence. Our data suggest the potential threat of the epidemic ST37 strains in China.

艰难梭菌序列类型(ST)37株,主要包括PCR核糖型(RT)017,在中国大陆很普遍。我们的研究旨在比较来自中国的ST37型艰难梭菌流行株(Xy06)与特征明确的艰难梭菌参考株R20291(RT027)和CD630E(ST54),以及从同一医院分离的中国ST54株(Xy07)的主要毒力因子。据预测,Xy06 基因组包含两个完整的原噬菌体和几个类转座子元件。PaLoc的比较分析显示了一个截短的tcdA基因、一个功能性的tcdB基因、一个功能性的tcdC基因以及保存完好的tcdR和tcdE基因。表型比较显示,Xy06 是 TcdB 的强力生产者,易于孢子化和发芽,并与人类肠道上皮细胞紧密结合。在艰难梭菌感染的小鼠模型中,Xy06 比 CD630E 和 Xy07 毒力更强,与 R20291 毒株的毒力相当。我们的数据表明,在中国流行的ST37菌株具有潜在威胁。
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引用次数: 0
Editorial: The infection and immunity of sexually transmitted disease pathogens. 社论:性传播疾病病原体的感染与免疫。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1498441
Shuping Hou
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引用次数: 0
Editorial: Antiviral options for emerging and reemerging viral diseases: current therapeutics, novel drug candidates and new approaches. 社论:新发和再发病毒性疾病的抗病毒选择:当前疗法、新型候选药物和新方法。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1497018
Clement Meseko, Melvin Sanicas, Yash Gupta, Binod Kumar
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引用次数: 0
Carbapenem-resistant Klebsiella oxytoca transmission linked to preoperative shaving in emergency neurosurgery, tracked by rapid detection via chromogenic medium and whole genome sequencing. 通过色原培养基快速检测和全基因组测序跟踪发现,耐碳青霉烯类克雷伯菌的传播与急诊神经外科术前剃毛有关。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1464411
Yun-Lan Jiang, Yi-Yu Lyu, Li-Li Liu, Zhi-Ping Li, Dan Liu, Jie-Hao Tai, Xiao-Qian Hu, Wen-Hui Zhang, Wen-Wen Chu, Xue Zhao, Wei Huang, Yi-Le Wu

Objectives: This study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO).

Methods: We conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory.

Results: The whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes bla KPC-2 and bla OXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred.

Conclusion: Contaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality.

研究目的本研究介绍了检测和追踪神经外科急诊交叉感染耐碳青霉烯类克雷伯菌(CRKO)的方法:我们开展了一项流行病学调查,并使用色原选择培养基对 66 份监测样本进行了快速筛查。方法:我们进行了流行病学调查,并使用色原选择培养基对 66 份监测样本进行了快速筛查。结果发现,来自感染患者的两份 CRKO 分离物和术前剃须刀中的三份分离物与临床实验室确定的耐药性特征相似:全基因组测序(WGS)结果表明,所有分离株均为密歇根克雷伯菌(K. oxytoca complex中的一个菌种),序列类型为29(ST29),携带耐药基因bla KPC-2和bla OXY-5以及IncF质粒。5 个分离物的核苷酸配对平均同一性值介于 99.993% 与 99.999% 之间。此外,在核心基因组多焦点序列分型方案的 5 229 个目标中,这些分离物的最大基因差异为 3,因此确认剃须刀为污染源。在实施控制措施和标准化剃须程序后,没有再发生新的 CRKO 感染:结论:受污染的剃须刀可能是神经外科手术部位感染 CRKO 的来源,因此需要建立标准的剃须程序。变色选择性培养基有助于快速鉴定目标病原体,而 WGS 技术则是在流行病或疫情调查中追踪传播源的有效手段。我们的研究结果增加了人们对手术中微生物传播的了解,从而提高了患者护理质量。
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引用次数: 0
Isolation and pathogenicity of a highly virulent group III porcine Getah virus in China. 中国高致病性Ⅲ群猪Getah病毒的分离和致病性。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1494654
Yu Wu, Xiaopeng Gao, Zhanpeng Kuang, Limiao Lin, Hao Zhang, Lijuan Yin, Jiabing Hong, Bohua Ren, Qunhui Li, Lianxiang Wang

Introduction: Getah virus (GETV) is a multi-host virus found in pigs, horses, and blue foxes. Clinically, GETV can cause fever, diarrhea, and reproductive disorders in pigs, representing significant threats to pig breeding. At present, few studies have examined the pathogenicity of GETV in pigs of different ages.

Methods: In the present study, a new strain, named GETV-QJ, was isolated from clinically ill pigs, and whole genome sequencing analysis was performed. Besides the pathogenicity of piglets and pregnant sows of this strain was further studied.

Results: the results illustrated that the strain belonged to group III. The strain had 93.6%-96.3% homology with other subtypes, and its homology with the same subtype strain ranged 96.5%-99%. Further studies on the pathogenicity of the virus indicated that this strain caused severe diarrhea, fever, and intestinal and lung damage in 7-day-old piglets, resulting in their death. The piglet survival rate was 0%. In pregnant sows, this strain did not cause fever, death, or abortion, but it induced viremia, which affected the farrowing performance of sows and led to reduced piglet survival.

Discussion: In this study, we isolated a highly virulent group III and comprehensively established a pathogenic model of GETV in piglets and sows, providing a reference and guidance for the prevention and control of this infection.

简介格塔病毒(GETV)是一种多宿主病毒,在猪、马和蓝狐中均有发现。在临床上,GETV 可导致猪发烧、腹泻和繁殖障碍,对养猪业构成严重威胁。目前,很少有研究探讨 GETV 在不同年龄猪中的致病性:本研究从临床病猪中分离出一株名为 GETV-QJ 的新毒株,并进行了全基因组测序分析。结果:研究结果表明,该毒株属于 III 群。该菌株与其他亚型的同源性为 93.6%-96.3%,与同亚型菌株的同源性为 96.5%-99%。对该病毒致病性的进一步研究表明,该毒株可引起 7 日龄仔猪严重腹泻、发热、肠道和肺损伤,导致仔猪死亡。仔猪存活率为 0%。在怀孕母猪中,该毒株不会引起发烧、死亡或流产,但会诱发病毒血症,影响母猪的产仔性能,导致仔猪存活率降低:本研究分离了高致病性的Ⅲ群病毒,全面建立了仔猪和母猪 GETV 的致病模型,为该病毒感染的防控提供了参考和指导。
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引用次数: 0
Novel management of pseudomonas biofilm-like structure in a post-pneumonectomy empyema. 肺切除术后气肿中假单胞菌生物膜样结构的新处理方法。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1458652
Alexandra M Gustafson, Carolina M Larrain, Lindsay R Friedman, Rachel Repkorwich, Ifeanyichukwu U Anidi, Karen M Forrest, Kevin P Fennelly, Shamus R Carr

We present a patient with a post-pneumonectomy empyema refractory to surgical debridement and systemic antibiotics. The patient initially presented with a bronchopleural fistula and pneumothorax secondary to tuberculosis (TB) destroyed lung, which required a pneumonectomy with Eloesser flap. Ongoing pleural infection delayed the closure of the Eloesser flap, and thoracoscopic inspection of his chest cavity revealed a green, mucous biofilm-like structure lining the postpneumonectomy pleural cavity. Cultures identified pan-susceptible Pseudomonas aeruginosa. Despite debriding this biofilm-like structure and administering systemic antibiotics, the patient continued to show persistent signs of infection and regrowth of the film. We employed a novel approach to dissolve the biofilm-like structure using intrapleural dornase alfa followed by intrapleural antibiotic washes. After 3 weeks of daily washes, repeat inspection demonstrated the biofilm-like structure had completely resolved. Resolving the pseudomonas biofilm-like structure allowed permanent closure of his chest without further need for systemic antibiotics. At follow up 3 months later, he showed no sequalae. This treatment option can be an important adjunct to improve likelihood of chest closure in patients with post-pneumonectomy empyema that resists standard treatment options due to biofilm formation.

我们为您介绍一位肺切除术后气胸的患者,手术清创和全身抗生素治疗均无效。患者最初因肺结核(TB)毁损肺部而继发支气管胸膜瘘和气胸,需要进行带Eloesser瓣的肺切除术。持续的胸膜感染延误了 Eloesser 皮瓣的闭合,胸腔镜检查发现肺切除术后的胸膜腔内衬有绿色粘液生物膜样结构。培养发现了泛感性铜绿假单胞菌。尽管清除了这种生物膜样结构并使用了全身抗生素,但患者仍出现持续感染和薄膜再生的迹象。我们采用了一种新方法来溶解生物膜样结构,即使用胸膜内多纳酶 alfa,然后进行胸膜内抗生素清洗。每天清洗 3 周后,重复检查显示生物膜样结构已完全溶解。假单胞菌生物膜样结构的消退使他的胸腔得以永久闭合,无需再使用全身抗生素。3 个月后的随访显示,他没有出现后遗症。对于因生物膜形成而无法接受标准治疗方案的肺切除术后肺水肿患者来说,这种治疗方案是一种重要的辅助手段,可提高胸部闭合的可能性。
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引用次数: 0
Global research trends and hotspots on human intestinal fungi and health: a bibliometric visualization study. 人类肠道真菌与健康的全球研究趋势和热点:文献计量学可视化研究。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1460570
Ming Gong, Huiying Yu, Hong Qu, Zhexian Li, Di Liu, Xin Zhao

Background: This article employs bibliometric methods and visual maps to delineate the research background, collaborative relationships, hotspots, and trends in the study of gut fungi in human diseases and health.

Methods: Publications related to human gut fungi were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, R software and Microsoft Excel were employed to generate visual representations illustrating the contributions made by countries/regions, authors, organizations, and journals. Employing VOSviewer and CiteSpace, we conducted a comprehensive analysis of the retrieved publications, revealing underlying tendencies, research hotspots, and intricate knowledge networks.

Results: This study analyzed a total of 3,954 publications. The United States ranks first in the number of published papers and has the highest number of citations and h-index. Mostafa S Elshahed is the most prolific author. The University of California System is the institution that published the most papers. Frontiers In Microbiology is the journal with the largest number of publications. Three frequently co-cited references have experienced a citation burst lasting until 2024.

Conclusion: Advancements in sequencing technologies have intensified research into human gut fungi and their health implications, shifting the research focus from gut fungal infections towards microbiome science. Inflammatory bowel diseases and Candida albicans have emerged as pivotal areas of interest in this endeavor. Through this study, we have gained a deeper insight into global trends and frontier hotspots within this field, thereby enhancing our understanding of the intricate relationship between gut fungi and human health.

背景:本文采用文献计量学方法和可视化地图来描述人类疾病和健康中肠道真菌研究的研究背景、合作关系、热点和趋势:方法:从 Web of Science Core Collection 中检索与人类肠道真菌相关的文献。使用 VOSviewer、CiteSpace、R 软件和 Microsoft Excel 生成可视化图表,说明国家/地区、作者、组织和期刊的贡献。利用 VOSviewer 和 CiteSpace,我们对检索到的出版物进行了全面分析,揭示了潜在趋势、研究热点和错综复杂的知识网络:本研究共分析了 3954 篇出版物。美国发表的论文数量居首位,引用次数和 h 指数也最高。Mostafa S Elshahed 是最多产的作者。加州大学系统是发表论文最多的机构。微生物学前沿》是发表论文数量最多的期刊。三篇经常被共同引用的参考文献的引文爆发期一直持续到 2024 年:测序技术的进步加强了对人类肠道真菌及其健康影响的研究,将研究重点从肠道真菌感染转向微生物组科学。炎症性肠病和白色念珠菌已成为这一研究的关键领域。通过这项研究,我们更深入地了解了这一领域的全球趋势和前沿热点,从而加深了我们对肠道真菌与人类健康之间错综复杂关系的理解。
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引用次数: 0
Ningxiang pigderived Enterococcus hirae regulates the inflammatory function and enhances the protection of piglets against ETEC challenge. 宁乡猪源性平肠球菌可调节炎症功能,增强仔猪对 ETEC 挑战的保护。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1476564
Longlin Zhang, Zichen Wu, Zihao Zhang, Rong Cai, Shujun Pang, Jing Wang, Xiyuan Bao

This study investigated the effects of Enterococcus hirae (Eh) derived from Ningxiang pigs on growth performance, diarrhea incidence, and immune responses in ETEC-challenged piglets. The results showed that compared to the CON group, ETEC infection significantly reduced the average daily gain (ADG) and average daily feed intake (ADFI), increased rectal temperature, and resulted in a diarrhea rate of up to 24%. Additionally, ETEC infection significantly increased the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of piglets. Compared to the ETEC group, orally Eh significantly increased ADFI in ETEC-infected piglets, reduced the diarrhea rate to 11.53%, reduced the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of ETEC-infected piglets. Furthermore, correlation analysis revealed that the levels of SCFAs (particularly acetate) were significantly negatively correlated with the expression levels of inflammatory cytokines in colonic and splenic tissues, suggesting that acetate may be a key metabolite in the anti-inflammatory effects of Eh. These results indicate that Eh can enhance the protection of piglets against ETEC K88 via intestine-acetate-spleen axis, thereby alleviating diarrhea and improving growth performance in piglets.

本研究调查了来自宁乡猪的平肠球菌(Eh)对ETEC挑战仔猪的生长性能、腹泻发生率和免疫反应的影响。结果表明,与 CON 组相比,ETEC 感染显著降低了平均日增重(ADG)和平均日采食量(ADFI),增加了直肠温度,导致腹泻率高达 24%。此外,ETEC 感染还显著增加了脾脏指数以及脾脏、血清和肠道中炎症细胞因子的表达,并降低了仔猪的血清 sIgA 和结肠 SCFA。与ETEC组相比,口服Eh可显著提高ETEC感染仔猪的ADFI,将腹泻率降低至11.53%,降低脾脏指数以及脾脏、血清和肠道中炎症细胞因子的表达,降低ETEC感染仔猪的血清sIgA和结肠SCFAs。此外,相关分析表明,SCFAs(尤其是乙酸盐)的水平与结肠和脾脏组织中炎症细胞因子的表达水平呈显著负相关,这表明乙酸盐可能是 Eh 抗炎作用的关键代谢物。这些结果表明,Eh 可通过肠-乙酸盐-脾轴增强仔猪对 ETEC K88 的保护,从而缓解腹泻并改善仔猪的生长性能。
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引用次数: 0
Corrigendum: Sensor histidine kinases kdpD and aauS regulate biofilm and virulence in Pseudomonas aeruginosa PA14. 更正:传感器组氨酸激酶 kdpD 和 aauS 调节铜绿假单胞菌 PA14 的生物膜和毒力。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1501233
Maria Sultan, Rekha Arya, Akhilesh Kumar Chaurasia, Kyeong Kyu Kim

[This corrects the article DOI: 10.3389/fcimb.2023.1270667.].

[此处更正了文章 DOI:10.3389/fcimb.2023.1270667]。
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引用次数: 0
期刊
Frontiers in Cellular and Infection Microbiology
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