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Biology and genetic diversity of Candida krusei isolates from fermented vegetables and clinical samples in China. 中国发酵蔬菜和临床样本中克鲁赛念珠菌分离物的生物学和遗传多样性。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-17 DOI: 10.1080/21505594.2024.2411543
Tianhong Zheng, Lingyu Ji, Yi Chen, Chengjun Cao, Jian Bing, Tianren Hu, Qiushi Zheng, Dan Wu, Haiqing Chu, Guanghua Huang

Candida krusei, also known as Pichia kudriavzevii, is an emerging non-albicans Candida (NAC) species causing both superficial and deep-seated infections in humans. This fungal pathogen is inherently resistant to the first-line antifungal drug, fluconazole, and is widely distributed in natural environments such as soil, foods, vegetables, and fruits. In this study, we collected 86 C. krusei strains from clinical settings and traditional fermented vegetables from different areas of China. Compared to C. krusei strains from fermented vegetables, clinical isolates exhibited a higher ability to undergo filamentation and biofilm development, which could facilitate its host colonization and infections. Isolates from fermented vegetables showed higher resistance to several antifungal drugs including fluconazole, voriconazole, itraconazole, amphotericin B, and caspofungin, than clinical strains, while they were more susceptible to posaconazole than clinical strains. Although C. krusei has been thought to be a diploid organism, we found that one-fourth of clinical strains and the majority of isolates from fermented vegetables (87.5%) are triploid. Whole-genome sequencing and population genetic analyses demonstrated that isolates from clinical settings and fermented food are genetically associated, and distributed across a wide range of genetic clusters. Additionally, we found that six nucleotide substitutions at the promoter region of the ABC11 gene, encoding a multidrug efflux pump, could play a critical role in antifungal resistance in this species. Given the ubiquitous distribution of C. krusei strains in fermented vegetables and their genetic association with clinical strains, a One Health approach will be necessary to control the prevalence of this pathogen.

克鲁塞念珠菌(Candida krusei),又名 Pichia kudriavzevii,是一种新出现的非白色念珠菌(NAC),可引起人类表皮和深部感染。这种真菌病原体本身对一线抗真菌药物氟康唑具有耐药性,并广泛分布于土壤、食物、蔬菜和水果等自然环境中。在这项研究中,我们从中国不同地区的临床环境和传统发酵蔬菜中收集了 86 株克鲁病菌。与发酵蔬菜中的克鲁赛菌株相比,临床分离菌株表现出更强的丝状化和生物膜发育能力,这有利于其在宿主体内定植和感染。与临床菌株相比,发酵蔬菜中的分离菌株对氟康唑、伏立康唑、伊曲康唑、两性霉素 B 和卡泊芬净等几种抗真菌药物的耐药性更高,而对泊沙康唑的敏感性则高于临床菌株。尽管克鲁塞菌一直被认为是二倍体生物,但我们发现四分之一的临床菌株和大多数从发酵蔬菜中分离出来的菌株(87.5%)都是三倍体。全基因组测序和群体遗传分析表明,来自临床环境和发酵食品的分离菌株在遗传上是相关联的,并分布在广泛的遗传集群中。此外,我们还发现,编码多药外排泵的 ABC11 基因启动子区域的六个核苷酸置换可能在该物种的抗真菌耐药性中起到关键作用。鉴于克鲁赛菌株在发酵蔬菜中的普遍分布及其与临床菌株的遗传关联,有必要采用 "一体健康 "方法来控制这种病原体的流行。
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引用次数: 0
The twin-arginine translocation system is vital for cell adhesion and uptake of iron in the cystic fibrosis pathogen Achromobacter xylosoxidans. 双精氨酸易位系统对囊性纤维化病原体木糖氧化无色杆菌的细胞粘附和铁的摄取至关重要。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1080/21505594.2023.2284513
S M Hossein Khademi, Cecilia Sahl, Lotta Happonen, Åke Forsberg, Lisa I Påhlman

Achromobacter xylosoxidans is an emerging pathogen that causes airway infections in patients with cystic fibrosis. Knowledge of virulence factors and protein secretion systems in this bacterium is limited. Twin arginine translocation (Tat) is a protein secretion system that transports folded proteins across the inner cell membranes of gram-negative bacteria. Tat has been shown to be important for virulence and cellular processes in many different bacterial species. This study aimed to investigate the role of Tat in iron metabolism and host cell adhesion in A. xylosoxidans. Putative Tat substrates in A. xylosoxidans were identified using the TatFind, TatP, and PRED-Tat prediction tools. An isogenic tatC deletion mutant (ΔtatC) was generated and phenotypically characterized. The wild-type and ΔtatC A. xylosoxidans were fractionated into cytosolic, membrane, and periplasmic fractions, and the expressed proteome of the different fractions was analysed using liquid chromatography-mass spectrometry (LC-MS/MS). A total of 128 putative Tat substrates were identified in the A. xylosoxidans proteome. The ΔtatC mutant showed attenuated host cell adhesion, growth rate, and iron acquisition. Twenty predicted Tat substrates were identified as expressed proteins in the periplasmic compartment, nine of which were associated with the wild type. The data indicate that Tat secretion is important for iron acquisition and host cell adhesion in A. xylosoxidans.

背景:氧化木糖无色杆菌是一种可引起囊性纤维化患者气道感染的新兴病原体。对这种细菌的毒力因子和蛋白质分泌系统的了解是有限的。双精氨酸易位(Tat)是一种蛋白质分泌系统,可在革兰氏阴性菌的细胞膜内转运折叠蛋白。它已被证明对许多不同细菌物种的毒力和细胞过程很重要。本研究旨在探讨Tat在木犀草铁代谢和寄主细胞粘附中的作用。方法:利用TatFind、TatP和PRED-Tat预测工具对木索酸a中推测的Tat底物进行鉴定。产生了一个等基因tatC缺失突变体(ΔtatC)并进行了表型表征。将野生型和ΔtatC木犀草分为细胞质、膜和质周三个部分,采用液相色谱-质谱联用(LC-MS/MS)分析不同部分的蛋白组表达。结果:在木犀草蛋白质组中共鉴定出128个推测的Tat底物。ΔtatC突变体显示宿主细胞粘附、生长速率和铁获取减弱。20个预测的Tat底物被鉴定为质周室的表达蛋白,其中9个与野生型相关。结论:木犀草的Tat分泌在铁获取和宿主细胞粘附中起重要作用。
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引用次数: 0
Recombination and amino acid point mutations in VP3 exhibit a synergistic effect on increased virulence of rMDPV. VP3 中的重组和氨基酸点突变对增强 rMDPV 的毒力具有协同作用。
IF 5.5 1区 农林科学 Q1 Immunology and Microbiology Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI: 10.1080/21505594.2024.2366874
Jianye Wang, Wanmei Li, Xiaoyan Gong, Zhixian Wang, Yu Wang, Jueyi Ling, Zhiwei Jiang, Guoqiang Zhu, Yufeng Li

Recombinant Muscovy duck parvovirus (rMDPV) is a product of genetic recombination between classical Muscovy duck parvovirus (MDPV) and goose parvovirus (GPV). The recombination event took place within a 1.1-kb DNA segment located in the middle of the VP3 gene, and a 187-bp sequence extending from the P9 promoter to the 5' initiation region of the Rep1 ORF. This resulted in the alteration of five amino acids within VP3. Despite these genetic changes, the precise influence of recombination and amino acid mutations on the pathogenicity of rMDPV remains ambiguous. In this study, based on the rMDPV strain ZW and the classical MDPV strain YY, three chimeric viruses (rZW-mP9, rZW-mPR187, and rYY-rVP3) and the five amino acid mutations-introduced mutants (rZW-g5aa and rYY-5aa(ZW)) were generated using reverse genetic technology. When compared to the parental virus rZW, rZW-g5aa exhibited a prolonged mean death time (MDT) and a decreased median lethal dose (ELD50) in embryonated duck eggs. In contrast, rYY-5aa(ZW) did not display significant differences in MDT and ELD50 compared to rYY. In 2-day-old Muscovy ducklings, infection with rZW-g5aa and rYY-5aa(ZW) resulted in mortality rates of only 20% and 10%, respectively, while infections with the three chimeric viruses (rZW-mP9, rZW-mPR187, rYY-rVP3) and rZW still led to 100% mortality. Notably, rYY-rVP3, containing the VP3 region from strain ZW, exhibited 50% mortality in 6-day-old Muscovy ducklings and demonstrated significant horizontal transmission. Collectively, our findings indicate that recombination and consequent amino acid changes in VP3 have a synergistic impact on the heightened virulence of rMDPV in Muscovy ducklings.

重组鸭副粘病毒(rMDPV)是经典鸭副粘病毒(MDPV)和鹅副粘病毒(GPV)基因重组的产物。重组事件发生在位于 VP3 基因中间的 1.1-kb DNA 片段以及从 P9 启动子延伸到 Rep1 ORF 的 5' 起始区的 187-bp 序列中。这导致了 VP3 中五个氨基酸的改变。尽管发生了这些基因变化,但重组和氨基酸突变对 rMDPV 致病性的确切影响仍不明确。本研究以 rMDPV 株系 ZW 和经典 MDPV 株系 YY 为基础,利用反向遗传技术生成了三种嵌合病毒(rZW-mP9、rZW-mPR187 和 rYY-rVP3)和五个氨基酸突变引入的突变体(rZW-g5aa 和 rYY-5aa(ZW))。与亲本病毒 rZW 相比,rZW-g5aa 的平均死亡时间(MDT)延长,胚胎鸭蛋的中位致死剂量(ELD50)降低。相比之下,rYY-5aa(ZW)与 rYY 相比,在 MDT 和 ELD50 方面没有显著差异。在 2 日龄的中华秋沙鸭中,感染 rZW-g5aa 和 rYY-5aa(ZW) 的死亡率分别仅为 20% 和 10%,而感染三种嵌合病毒(rZW-mP9、rZW-mPR187、rYY-rVP3)和 rZW 的死亡率仍为 100%。值得注意的是,含有 ZW 株 VP3 区域的 rYY-rVP3 在 6 日龄的麝香鸭中的死亡率为 50%,并表现出显著的水平传播。总之,我们的研究结果表明,VP3 的重组和随之而来的氨基酸变化对提高 rMDPV 在麝香鸭中的毒力具有协同作用。
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引用次数: 0
A shared mechanism of multidrug resistance in laboratory-evolved uropathogenic Escherichia coli. 实验室进化的尿路致病性大肠杆菌共同的多药耐药性机制。
IF 5.5 1区 农林科学 Q1 Immunology and Microbiology Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI: 10.1080/21505594.2024.2367648
Nakjun Choi, Eunna Choi, Yong-Joon Cho, Min Jung Kim, Hae Woong Choi, Eun-Jin Lee

The emergence of multidrug-resistant bacteria poses a significant threat to human health, necessitating a comprehensive understanding of their underlying mechanisms. Uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections, is frequently associated with multidrug resistance and recurrent infections. To elucidate the mechanism of resistance of UPEC to beta-lactam antibiotics, we generated ampicillin-resistant UPEC strains through continuous exposure to low and high levels of ampicillin in the laboratory, referred to as Low AmpR and High AmpR, respectively. Whole-genome sequencing revealed that both Low and High AmpR strains contained mutations in the marR, acrR, and envZ genes. The High AmpR strain exhibited a single additional mutation in the nlpD gene. Using protein modeling and qRT-PCR analyses, we validated the contributions of each mutation in the identified genes to antibiotic resistance in the AmpR strains, including a decrease in membrane permeability, increased expression of multidrug efflux pump, and inhibition of cell lysis. Furthermore, the AmpR strain does not decrease the bacterial burden in the mouse bladder even after continuous antibiotic treatment in vivo, implicating the increasing difficulty in treating host infections caused by the AmpR strain. Interestingly, ampicillin-induced mutations also result in multidrug resistance in UPEC, suggesting a common mechanism by which bacteria acquire cross-resistance to other classes of antibiotics.

耐多药细菌的出现对人类健康构成了重大威胁,因此有必要全面了解其基本机制。尿路感染的主要致病菌--尿路致病性大肠杆菌(UPEC)经常出现耐多药和反复感染。为了阐明 UPEC 对β-内酰胺类抗生素的耐药机制,我们在实验室中通过持续暴露于低浓度和高浓度的氨苄西林产生了耐氨苄西林的 UPEC 菌株,分别称为低 AmpR 和高 AmpR。全基因组测序显示,低AmpR和高AmpR菌株都含有marR、acrR和envZ基因突变。高 AmpR 菌株的 nlpD 基因也有一个突变。通过蛋白质建模和 qRT-PCR 分析,我们验证了已确定基因中的每个突变对 AmpR 菌株抗生素耐药性的贡献,包括膜渗透性降低、多药外排泵表达增加和细胞裂解抑制。此外,即使在体内持续使用抗生素治疗,AmpR 菌株也不会减少小鼠膀胱中的细菌负担,这表明由 AmpR 菌株引起的宿主感染越来越难以治疗。有趣的是,氨苄西林诱导的突变也会导致 UPEC 产生多药耐药性,这表明细菌获得对其他类抗生素交叉耐药性的共同机制。
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引用次数: 0
Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin. 耐妥布霉素的鼠伤寒沙门氏菌小菌落变异突变体对硝基呋喃妥因有附带敏感性。
IF 5.2 1区 农林科学 Q1 Immunology and Microbiology Pub Date : 2024-12-01 Epub Date: 2024-05-26 DOI: 10.1080/21505594.2024.2356692
Chang-Zhen Wang, Yue-Jun Zhang, Yue-Fei Chu, Long-Gen Zhong, Jin-Peng Xu, Liu-Yan Liang, Teng-Fei Long, Liang-Xing Fang, Jian Sun, Xiao-Ping Liao, Yu-Feng Zhou

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

抗生素耐药性的不断增加对全球健康构成了重大挑战,威胁着我们抗击传染病的能力。对一种抗生素产生耐药性的同时,对另一种抗生素的敏感性也随之增加,这种附带敏感性现象为治疗对传统疗法无反应的感染提供了新的潜在途径。在这项研究中,我们阐明了因 hemL 基因突变而出现的对妥布霉素(Tobramycin,TOB)耐药的小菌落变异体(SCVs),这种变异体使 S. Typhimurium 对硝基呋喃妥因(NIT)更敏感。机理研究表明,耐 TOB 的 S. Typhimurium SCVs 的附带敏感性主要源于血红素生物合成的中断。这导致电子传递链(ETC)功能失调和氧化还原失衡,最终诱发致命的活性氧(ROS)积累。此外,nfsA/B 表达的上调促进了 NIT 原药向其活性形式的转化,促进了 ROS 介导的细菌杀伤,并促成了这种附带敏感性模式。重要的是,在小鼠大腿感染和结肠炎模型中,NIT 替代疗法可显著减少细菌负荷,减少量超过 2.24-log10 cfu/g。我们的研究结果证实,由于对氨基糖苷类药物的耐药性不断发展,伤寒杆菌对硝基呋喃类药物具有附带敏感性。这为治疗耐氨基糖苷类药物菌株引起的感染提供了一种很有前景的方法。
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引用次数: 0
Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality. 苍白螺旋体上的血小板源性主要组织相容性复合体 I 类涂层可减轻自然杀伤细胞的致死率。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-14 DOI: 10.1080/21505594.2024.2350892
Qiu-Yan Xu, Xin-Qi Zheng, Wei-Ming Ye, Dong-Yu Yi, Ze Li, Qing-Qi Meng, Man-Li Tong, Dan Liu, Tian-Ci Yang

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

苍白盘尾丝菌的躲避策略给抗击和根除梅毒带来了重大挑战。为了弄清苍白螺旋体逃避NK介导的免疫监视的机制,研究人员进行了实验来探索苍白螺旋体、NK细胞和血小板之间的交叉对话关系。苍白球粘附、激活并促进血小板分泌微粒。与苍白球预孵育后,血小板表达并分泌高水平的 MHC I 类,随后将其转移到苍白球表面,可能诱导出一种以苍白球表面 MHC I 类 "伪表达"(以下简称 MHC I 类 "伪表达")为特征的免疫表型。polA mRNA 检测显示,血小板预培养 T. pallidum 组的 polA 转录本拷贝数明显高于 T. pallidum 组。T. pallidum的存活率与polA mRNA的存活率一致,这表明T. pallidum与血小板预孵育可减轻NK细胞的致死率。血小板在苍白球表面伪表达了MHC I类配体,促进了与NK细胞上具有两个免疫球蛋白结构域和长胞质尾3(KIR2DL3)的杀伤细胞免疫球蛋白样受体的结合,并启动了Vav1的去磷酸化和Crk的磷酸化,最终降低了NK细胞的致死率。我们的发现阐明了血小板将 MHC I 类转移到苍白球表面以逃避 NK 细胞免疫清除的机制。
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引用次数: 0
Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent Klebsiella pneumoniae. 一种不产碳青霉烯酶的 K1-ST23 型高病毒性肺炎克雷伯菌对头孢他啶-阿维菌素敏感性的丧失和增益。
IF 5.2 1区 农林科学 Q1 Immunology and Microbiology Pub Date : 2024-12-01 Epub Date: 2024-05-02 DOI: 10.1080/21505594.2024.2348251
Jiankang Zhao, Danni Pu, Ziyao Li, Yulin Zhang, Xinmeng Liu, Xianxia Zhuo, Binghuai Lu, Bin Cao

Objectives: This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp).

Methods: Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.

Results: Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes blaCTX-M-15 and blaCTX-M-71, respectively, but KP30086 lost both. Cloning of gene blaCTX-M-71 and conjugation experiment of blaCTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.

Conclusions: In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying blaCTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.

研究目的本研究旨在揭示非碳青霉烯酶生产型高病毒性肺炎克雷伯菌(hvKp)对头孢他啶-阿维巴坦易感性丧失和增益的内在机制。方法:我们从一名老年男性患者身上纵向采集了3株非碳青霉烯酶生产型K1-ST23 hvKp菌株(KP29105、KP29499和KP30086),间隔时间为一个月。研究人员对这些菌株进行了抗菌药敏感性检测、全基因组测序、转录组测序、基因克隆、质粒连接、实时定量 PCR(qRT-PCR)和 SDS-PAGE(十二烷基硫酸钠-聚丙烯酰胺凝胶电泳):结果:在3株hvKp菌株中,KP29105对第三代和第四代头孢菌素耐药,KP29499对头孢唑肟-阿维巴坦和碳青霉烯类耐药,而KP30086恢复了对头孢唑肟-阿维巴坦、亚胺培南和美罗培南的敏感性,但对厄他培南保持低水平耐药。KP29105 和 KP29499 分别携带质粒编码基因 blaCTX-M-15 和 blaCTX-M-71,但 KP30086 却失去了这两种基因。基因 blaCTX-M-71 的克隆和携带 blaCTX-M-71 的质粒的共轭实验表明,转化株和转接株对头孢他啶-阿维巴坦敏感,但 MICs 增加了 8 倍多。添加外膜渗透剂可使头孢他啶-阿维菌素的 MIC 降低 32 倍,表明孔蛋白在头孢他啶-阿维菌素耐药性中起着关键作用。这 3 个分离株的 OmpK35 没有表达,KP29499 和 KP30086 的 OmpK36 有一个新的氨基酸取代(L359R)。SDS-PAGE和qRT-PCR显示,与KP29105相比,KP29499和KP30086的孔蛋白OmpK36表达明显下调:综上所述,我们报道了非碳青霉烯酶产hvKp菌株对头孢他啶-阿维菌素的罕见耐药性。携带 blaCTX-M-71 和突变 OmpK36 的耐药质粒对耐药性有协同作用。
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引用次数: 0
Pathogenicity and virulence of chikungunya virus. 基孔肯雅病毒的致病性和毒性。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-01 DOI: 10.1080/21505594.2024.2396484
Wesley Freppel, Laurie A Silva, Kenneth A Stapleford, Lara J Herrero

Chikungunya virus (CHIKV) is a mosquito-transmitted, RNA virus that causes an often-severe musculoskeletal illness characterized by fever, joint pain, and a range of debilitating symptoms. The virus has re-emerged as a global health threat in recent decades, spreading from its origin in Africa across Asia and the Americas, leading to widespread outbreaks impacting millions of people. Despite more than 50 years of research into the pathogenesis of CHIKV, there is still no curative treatment available. Current management of CHIKV infections primarily involves providing supportive care to alleviate symptoms and improve the patient's quality of life. Given the ongoing threat of CHIKV, there is an urgent need to better understand its pathogenesis. This understanding is crucial for deciphering the mechanisms underlying the disease and for developing effective strategies for both prevention and management. This review aims to provide a comprehensive overview of CHIKV and its pathogenesis, shedding light on the complex interactions of viral genetics, host factors, immune responses, and vector-related factors. By exploring these intricate connections, the review seeks to contribute to the knowledge base surrounding CHIKV, offering insights that may ultimately lead to more effective prevention and management strategies for this re-emerging global health threat.

基孔肯雅病毒(CHIKV)是一种由蚊子传播的 RNA 病毒,通常会引起严重的肌肉骨骼疾病,其特征是发烧、关节疼痛和一系列使人衰弱的症状。近几十年来,该病毒再次成为全球健康威胁,从非洲传播到亚洲和美洲,导致疫情大面积爆发,影响数百万人。尽管对 CHIKV 的发病机理进行了五十多年的研究,但目前仍没有治疗方法。目前对 CHIKV 感染的治疗主要是提供支持性护理,以减轻症状并提高患者的生活质量。鉴于 CHIKV 的持续威胁,迫切需要更好地了解其发病机制。这种了解对于破译该疾病的发病机制以及制定有效的预防和管理策略至关重要。本综述旨在全面概述 CHIKV 及其发病机制,揭示病毒遗传学、宿主因素、免疫反应和病媒相关因素之间复杂的相互作用。通过探讨这些错综复杂的联系,本综述力图为有关 CHIKV 的知识库做出贡献,并提供见解,最终为这一重新出现的全球健康威胁制定更有效的预防和管理策略。
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引用次数: 0
Oral inoculation of Fusobacterium nucleatum exacerbates ulcerative colitis via the secretion of virulence adhesin FadA. 通过分泌毒力粘附素 FadA,口服接种核酸镰刀菌会加重溃疡性结肠炎。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-09 DOI: 10.1080/21505594.2024.2399217
Donghao Li, Zongwei Li, Lei Wang, Yan Zhang, Shoubin Ning

Fusobacterium nucleatum (F. nucleatum), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of F. nucleatum are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral F. nucleatum in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of F. nucleatum strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with F. nucleatum facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen F. nucleatum and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.

核滑杆菌(Fusobacterium nucleatum,F. nucleatum)是口腔中的一种厌氧居民,越来越被认为是溃疡性结肠炎(UC)的致病因素。核酸杆菌的粘附特性是由其关键毒力蛋白 FadA 粘合素介导的。然而,要了解这种口腔病原体在溃疡性结肠炎中的致病机制还需要进一步研究。本研究旨在通过分子技术探讨 FadA 粘附蛋白在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠口腔核酸桿菌定植和入侵中的作用。在这项研究中,我们发现口腔接种携带 FadA 黏附因子的 F. nucleatum 菌株会进一步加剧右旋糖酐硫酸钠(DSS)诱导的结肠炎,导致牙槽骨损失、疾病严重程度和死亡率升高。此外,CDH1 基因敲除小鼠经 DSS 治疗后,体重和牙槽骨密度增加,疾病严重程度降低。此外,FadA粘附蛋白与其粘膜受体E-cadherin粘附,导致β-catenin磷酸化、IκBα降解、NF-κB信号通路激活和下游细胞因子上调。总之,这项研究揭示了口腔接种F. nucleatum可通过分泌毒力粘附素FadA促进实验性结肠炎的发生。针对口腔病原体F. nucleatum及其毒力因子FadA可能是治疗部分UC患者的一种很有前景的方法。
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引用次数: 0
ATP synthase subunit ATP5B interacts with TGEV Nsp2 and acts as a negative regulator of TGEV replication. ATP 合成酶亚基 ATP5B 与 TGEV Nsp2 相互作用,是 TGEV 复制的负调控因子。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-09 DOI: 10.1080/21505594.2024.2397492
Yanan Wang, Aoying Sun, Yaru Guo, Lingxiang Xin, Yanping Jiang, Wen Cui, Jiaxuan Li, Yijing Li, Li Wang

Coronavirus nonstructural protein 2 (Nsp2) is regarded as a virulence determinant and plays a critical role in virus replication, and innate immunity. Screening and identifying host cell proteins that interact with viral proteins is an effective way to reveal the functions of viral proteins. In this study, the host proteins that interacted with transmissible gastroenteritis virus (TGEV) Nsp2 were identified using immunoprecipitation combined with LC-MS/MS. 77 host cell proteins were identified as putative Nsp2 interaction host cell proteins and a protein-protein interaction (PPI) was constructed. The identified proteins were found to be associated with various subcellular locations and functional categories through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. It is hypothesized that the host cell proteins interacting with TGEV Nsp2 are mainly involved in the formation of the cytoplasmic translation initiation complex, mRNA binding, ribosomes, and proteasomes. Among these, the ATP5B, a core subunit of the mitochondrial ATP synthase was further studied. The Coimmunoprecipitation (Co-IP) and indirect immunofluorescence (IFA) results confirmed that TGEV Nsp2 interacted with ATP5B. Furthermore, the downregulation of ATP5B expression was found to promote TGEV replication, suggesting that ATP5B might function as a negative regulator of TGEV replication. Collectively, our results offer additional insights into the functions of Nsp2 and provide a novel antiviral target against TGEV.

冠状病毒非结构蛋白2(Nsp2)被认为是一种毒力决定因子,在病毒复制和先天免疫中发挥着关键作用。筛选和鉴定与病毒蛋白相互作用的宿主细胞蛋白是揭示病毒蛋白功能的有效方法。本研究利用免疫沉淀和 LC-MS/MS 方法鉴定了与传染性胃肠炎病毒(TGEV)Nsp2 相互作用的宿主蛋白。77 个宿主细胞蛋白被鉴定为推定的 Nsp2 相互作用宿主细胞蛋白,并构建了蛋白质-蛋白质相互作用(PPI)。通过基因本体(GO)和京都基因和基因组百科全书(KEGG)富集分析,发现所鉴定的蛋白质与不同的亚细胞位置和功能类别相关。据推测,与 TGEV Nsp2 相互作用的宿主细胞蛋白主要参与细胞质翻译起始复合体、mRNA 结合、核糖体和蛋白酶体的形成。其中,线粒体 ATP 合成酶的核心亚基 ATP5B 被进一步研究。免疫共沉淀(Co-IP)和间接免疫荧光(IFA)结果证实,TGEV Nsp2 与 ATP5B 相互作用。此外,研究还发现 ATP5B 的表达下调会促进 TGEV 的复制,这表明 ATP5B 可能是 TGEV 复制的负调控因子。总之,我们的研究结果为了解 Nsp2 的功能提供了新的视角,并为 TGEV 提供了一个新的抗病毒靶点。
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引用次数: 0
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Virulence
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