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Adapted evolution towards flagellar loss in Pseudomonas syringae. 丁香假单胞菌失去鞭毛的适应性进化。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-16 DOI: 10.1016/j.micres.2024.127969
Jiarong Wang, Xiaoquan Yu, Hao Yang, Hanzhong Feng, Yujuan Wang, Nannan Zhang, Haining Xia, Jie Li, Lei Xing, Junfeng Wang, Yongxing He

The flagellum is a complex molecular nanomachine crucial for cell motility. Its assembly requires coordinated expression of over 50 flagellar genes, regulated by the transcription activator FleQ. Phylogenomic analyses suggest that many non-flagellated bacterial species have evolved from flagellated ancestors by losing specific flagellar components, though the evolutionary mechanisms driving this process remain unclear. In this study, we examined the evolutionary dynamics of Pseudomonas syringae DC3000 under standard laboratory conditions using quantitative proteomics. We observed a notable reduction in flagellar gene expression following prolonged serial passages. Whole-genome sequencing revealed multiple adaptive mutations in fleQ, dksA, and glnE, all of which are associated with flagellar biosynthesis. Furthermore, our findings demonstrate that nonmotile ΔfleQ cells can hitchhike onto wild-type cells, potentially facilitated by increased production of the surfactant syringafactin. Our study suggests that the high metabolic costs associated with flagella biosynthesis, coupled with advantageous hitchhiking properties, contribute to the degenerative evolution of flagella.

鞭毛是一种复杂的分子纳米机械,对细胞运动至关重要。它的组装需要 50 多个鞭毛基因的协调表达,并受转录激活因子 FleQ 的调控。系统发生组分析表明,许多无鞭毛细菌物种是从有鞭毛的祖先进化而来的,它们失去了特定的鞭毛成分,但驱动这一过程的进化机制仍不清楚。在本研究中,我们利用定量蛋白质组学研究了标准实验室条件下丁香假单胞菌 DC3000 的进化动态。我们观察到,在长期连续传代后,鞭毛基因表达明显减少。全基因组测序发现了 fleQ、dksA 和 glnE 中的多个适应性突变,这些突变都与鞭毛的生物合成有关。此外,我们的研究结果表明,非运动型的ΔfleQ细胞可以搭便车到野生型细胞上,这可能是由于表面活性物质鞘氨醇的产量增加所致。我们的研究表明,与鞭毛生物合成相关的高代谢成本,加上有利的搭便车特性,促成了鞭毛的退化进化。
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引用次数: 0
Role of gut microbiota in rheumatoid arthritis: Potential cellular mechanisms regulated by prebiotic, probiotic, and pharmacological interventions 肠道微生物群在类风湿关节炎中的作用:益生菌、益生菌和药物干预调控的潜在细胞机制。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.micres.2024.127973
Jiashang Li, Ruoying Fan, Zhe Zhang, Lihui Zhao, Yu Han, Yue Zhu, Jin-ao Duan, Shulan Su
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects joints and multiple organs and systems, which is long-lasting and challenging to cure and significantly impacting patients' quality of life. Alterations in the composition of intestinal flora in both preclinical and confirmed RA patients indicate that intestinal bacteria play a vital role in RA immune function. However, the mechanism by which the intestinal flora is regulated to improve the condition of RA is not fully understood. This paper reviews the methods of regulating gut microbiota and its metabolites through prebiotics, probiotics, and pharmacological interventions, and discusses their effects on RA. Additionally, it explores the potential predictive role of cellular therapy mechanisms of intestinal flora in treating RA. These findings suggest that restoring the ecological balance of intestinal flora and regulating intestinal barrier function may enhance immune system function, thereby improving rheumatoid arthritis. This offers new insights into its treatment.
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,主要影响关节及多个器官和系统,病程长,治愈难度大,严重影响患者的生活质量。临床前和确诊的 RA 患者肠道菌群组成的改变表明,肠道细菌在 RA 免疫功能中发挥着重要作用。然而,调节肠道菌群以改善 RA 病情的机制尚未完全明了。本文回顾了通过益生菌、益生菌和药物干预来调节肠道微生物群及其代谢产物的方法,并讨论了它们对 RA 的影响。此外,本文还探讨了肠道菌群的细胞治疗机制在治疗 RA 方面的潜在预测作用。这些研究结果表明,恢复肠道菌群的生态平衡和调节肠道屏障功能可增强免疫系统功能,从而改善类风湿关节炎。这为类风湿关节炎的治疗提供了新的思路。
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引用次数: 0
Synergistic effect of Adathoda vasica plant-derived biostimulant and PGPR on Zea mays L. for drought stress management Adathoda vasica 植物源生物刺激剂和 PGPR 对玉米干旱胁迫管理的协同效应。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.micres.2024.127968
Abhilasha Mishra, Srishti Kar, Nikita Bisht, Shashank Kumar Mishra, Puneet Singh Chauhan
Drought is a significant abiotic stress that adversely affects the physiological and biochemical processes in crops, posing a considerable challenge to agricultural productivity. The present study explored the efficacy of plant-derived biostimulant (PDB) and plant growth-promoting rhizobacteria (PGPR) strains Pseudomonas putida (RA) and Paenibacillus lentimorbus CHM12) in the management of negative impacts of drought stress in Zea mays (maize). Adathoda vasica leaf extracts (ADLE) emerged as the most potent biostimulant of the seven evaluated medicinal plant extracts. The synergetic effect of ADLE and RA enhances plant vegetative growth (root length, shoot length, fresh weight and dry weight) as well as significantly modulates drought-induced oxidative stress, as indicated by higher chlorophyll content and increased sugar and phenolic levels and reduction of proline level. The expression of defence-related (ZmAPX, ZmSOD, and ZmCAT) and transcription factor (ZmNAC, ZmWRKY, and ZmMYB) genes further supported the beneficial effects of this synergism under drought conditions. Furthermore, metabolite profiling through GC-MS analysis showed significant alterations in metabolites such as glucose, galactose, mannose, hexopyranose, linolenic acid, hexadecenoic acid, and butanedioic acid when PDB and PGPR were applied together. Overall, the findings of the present study affirm that the combined application of plant-derived biostimulant ADLE and plant-beneficial rhizobacteria RA can effectively alleviate the adverse effects of drought on maize, providing an eco-friendly and sustainable solution for improving productivity under stress.
干旱是一种严重的非生物胁迫,会对农作物的生理和生化过程产生不利影响,给农业生产带来巨大挑战。本研究探讨了植物源生物刺激剂(PDB)和植物生长促进根瘤菌(PGPR)菌株假单胞菌(RA)和Paenibacillus lentimorbus CHM12在管理玉米干旱胁迫负面影响方面的功效。Adathoda vasica 叶提取物(ADLE)是七种受评估药用植物提取物中最有效的生物刺激剂。ADLE 和 RA 的协同作用增强了植物的无性生长(根长、芽长、鲜重和干重),并显著调节了干旱引起的氧化应激,表现为叶绿素含量增加、糖和酚含量增加以及脯氨酸含量降低。防御相关基因(ZmAPX、ZmSOD 和 ZmCAT)和转录因子(ZmNAC、ZmWRKY 和 ZmMYB)的表达进一步证实了这种协同作用在干旱条件下的有益效果。此外,通过 GC-MS 分析进行的代谢物分析表明,当 PDB 和 PGPR 同时应用时,葡萄糖、半乳糖、甘露糖、六吡喃糖、亚麻酸、十六碳烯酸和丁二酸等代谢物发生了显著变化。总之,本研究的结果肯定了联合应用植物源生物刺激剂 ADLE 和植物有益根瘤菌 RA 能有效缓解干旱对玉米的不利影响,为提高胁迫下的生产力提供了一种生态友好和可持续的解决方案。
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引用次数: 0
The LysR-type transcriptional factor PacR controls heterocyst differentiation and C/N metabolism in the cyanobacterium Anabaena PCC 7120. LysR 型转录因子 PacR 控制着蓝藻 Anabaena PCC 7120 的异囊分化和 C/N 代谢。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.micres.2024.127970
Gui-Ming Lin, Ju-Yuan Zhang, Zhi-Hui Shao, Chen Yang, Guo-Ping Zhao, Kai-Yao Huang, Cheng-Cai Zhang

PacR (All3953) has previously been identified as a global transcriptional regulator of carbon assimilation in cyanobacteria. In the facultative diazotrophic and filamentous cyanobacterium Anabaena PCC 7120 (Anabaena), inactivation of pacR has been shown to affect cell growth under various conditions. Nitrogen fixation in Anabaena occurs in heterocysts, cells differentiated semiregularly along the filaments following deprivation of combined nitrogen such as nitrate or ammonium. Here, we created a markerless deletion mutant of pacR. In addition to its growth defects observed under different light and nitrogen conditions, the mutant could form a high frequency of heterocysts, including heterocyst doublets, even in the presence of nitrate. Inactivation of pacR led to the upregulation of ntcA, a global regulator of nitrogen metabolism and heterocyst formation, as well as downregulation of genes involved in nitrate uptake and assimilation. These changes led to N-limited cells in the presence of nitrate. PacR also regulates most of the genes encoding bicarbonate transport systems. The promoter regions of ntcA, and several other genes involved in nitrogen or carbon uptake and assimilation, as well as patS and hetN involved in heterocyst patterning can be directly recognized by PacR in vitro. These findings, along with previously reported ChIP-seq data, establish PacR as a crucial transcriptional regulator for balancing carbon and nitrogen metabolism in cyanobacteria.

PacR (All3953) 是蓝藻中碳同化的全局转录调控因子。在兼性重氮营养丝状蓝藻 Anabaena PCC 7120(Anabaena)中,pacR 的失活已被证明会影响细胞在各种条件下的生长。Anabaena 的固氮作用是在异囊中进行的,异囊细胞在硝酸盐或铵盐等复合氮被剥夺后沿丝状体半圆形分化。在这里,我们创建了一个无标记的 pacR 缺失突变体。除了在不同光照和氮素条件下观察到的生长缺陷外,该突变体即使在硝酸盐存在的情况下也能形成高频率的异囊,包括异囊双胞。pacR 失活导致氮代谢和杂囊形成的全局调控因子 ntcA 上调,以及参与硝酸盐吸收和同化的基因下调。这些变化导致细胞在硝酸盐存在的情况下出现氮限制。PacR 还调控大多数编码碳酸氢盐转运系统的基因。体外 PacR 可直接识别 ntcA 和其他几个参与氮或碳吸收和同化的基因的启动子区域,以及参与异囊模式化的 patS 和 hetN。这些发现以及之前报道的 ChIP-seq 数据证实,PacR 是平衡蓝藻碳氮代谢的关键转录调控因子。
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引用次数: 0
Coagulase-Negative Staphylococci phages panorama: Genomic diversity and in vitro studies for a therapeutic use 凝固酶阴性葡萄球菌噬菌体全景:基因组多样性和用于治疗的体外研究。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.micres.2024.127944
Maria Sequeira Lopes , Maria Daniela Silva , Joana Azeredo , Luís D.R. Melo
Coagulase-negative staphylococci (CoNS) are commensal bacteria of the human skin and mucosal membranes. The incidence of nosocomial infections caused by these species is on the rise, leading to a potential increase in antibiotic tolerance and resistance. Phages are emerging as a promising alternative to combat CoNS infections. Scientists are isolating phages infecting CoNS with a particular interest in S. epidermidis. This review compiles and analyses CoNS phages for several parameters including source, geographical location, host species, morphological diversity, and genomic diversity. Additionally, recent studies have highlighted the potential of these phages based on host range, in vitro evaluation of performance and stability, and interaction with biofilms. This comprehensive analysis enables a better understanding of the steps involved in using these phages for therapeutic purposes.
凝固酶阴性葡萄球菌(CoNS)是人类皮肤和粘膜的共生细菌。由这些细菌引起的院内感染发病率呈上升趋势,可能导致抗生素耐受性和抗药性的增加。噬菌体正在成为抗 CoNS 感染的一种有前途的替代品。科学家们正在分离感染 CoNS 的噬菌体,尤其关注表皮葡萄球菌。本综述汇编并分析了 CoNS 噬菌体的几个参数,包括来源、地理位置、宿主种类、形态多样性和基因组多样性。此外,最近的研究还根据宿主范围、体外性能和稳定性评估以及与生物膜的相互作用,强调了这些噬菌体的潜力。这种全面的分析有助于更好地了解将这些噬菌体用于治疗的步骤。
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引用次数: 0
Deciphering intricate plant-virus interactions: Potyvirids orchestrate protein posttranslational modifications to regulate pathogenicity 解密植物与病毒之间错综复杂的相互作用:Potyvirids协调蛋白质翻译后修饰以调节致病性。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-08 DOI: 10.1016/j.micres.2024.127940
Ali kamran , Muhammad Dilshad Hussain , Tahir Farooq , Fangfang Li , Mehran Khan , Xiangyang Li , Sanwei Yang , Xin Xie
In a molecular-arm-race between viruses and their hosts, viruses have evolved to harness their host's post-translational modifications (PTMs) machinery to gain a competitive edge. These modifications are the most reliable target of plant viruses to overcome the host defence for successful infection. Relatively fewer PTMs i.e., phosphorylation, O-GlcNAcylation, Ubiquitination, and SUMOylation have been studied regulating the potyvirus-plant interaction. Therefore, it is worth drawing attention towards the importance and potential of this undermined but key strategy of potyvirids (members of family Potyviridae) to abduct their host defence line, suggesting to review in detail the existing knowledge of these PTMs and highlight the unexplored modifications that might have played their part in establishing successful infection. The current review provides an understanding of how PTMs execute viral replication and infection dynamics during plant-potyvirid interactions. We highlighted that PTMs linked to CP, NIa-pro, NIb, and VPg are important to specify their host, virulence, overcoming host innate immunity, and most importantly disarming the host of RNA silencing tool of nailing any intruder. The limitations and potential improvements in studying undermined PTMs, including acetylation, glycosylation, methylation, and neddylation, as well as challenges and future perspectives of this inevitable process are mechanistically deciphered in the course of plant-virus interactions. This communication opens new avenues for investigating the fundamental mechanisms of virus infection and the development of new antiviral strategies for sustainable disease managements.
在病毒与其宿主之间的分子军备竞赛中,病毒已经进化到利用宿主的翻译后修饰(PTMs)机制来获得竞争优势。这些修饰是植物病毒克服宿主防御以成功感染的最可靠目标。目前对调控植物病毒与植物相互作用的 PTMs(即磷酸化、O-GlcNAcylation、泛素化和 SUMOylation)的研究相对较少。因此,值得注意的是,壶状病毒(壶状病毒科成员)绑架宿主防线的这一被削弱但却关键的策略的重要性和潜力,建议详细回顾这些 PTMs 的现有知识,并强调可能在建立成功感染中发挥作用的未探索的修饰。本综述介绍了 PTMs 如何在植物-植物病毒相互作用过程中执行病毒复制和感染动态。我们强调,与 CP、NIa-pro、NIb 和 VPg 相关的 PTM 对于指定宿主、毒力、克服宿主先天免疫以及最重要的解除宿主的 RNA 沉默工具以钉死任何入侵者都很重要。在植物-病毒相互作用的过程中,研究被破坏的 PTMs(包括乙酰化、糖基化、甲基化和内切酶化)的局限性和潜在改进,以及这一不可避免的过程所面临的挑战和未来展望,都将从机理上得到破解。这篇通讯为研究病毒感染的基本机制以及为可持续的疾病管理开发新的抗病毒策略开辟了新的途径。
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引用次数: 0
The hex1 gene of Trichoderma simmonsii is involved in stress responses, biocontrol potential and wheat plant growth 西蒙氏毛霉的 hex1 基因参与了胁迫反应、生物控制潜力和小麦植物生长。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.micres.2024.127958
Alberto Pedrero-Méndez, María Illescas, Enrique Monte, Rosa Hermosa
Woronin bodies are unique organelles in Pezizomycotina fungi that allow hyphae compartmentalization and prevent cytoplasmatic bleeding after mechanical injury. Several studies have related the peroxisomal protein HEX1, the major component of Woronin bodies with other biological processes such as hyphal growth, osmotic stress tolerance and pathogenicity. Trichoderma spp. are plant-beneficial multipurpose biological control agents, and proteomic and transcriptomic studies have shown that HEX1 and its corresponding gene are overrepresented when grown in the presence of fungal cell walls and plant polymers. To further investigate the involvement of hex1 in Trichoderma biology, we generated hex1 deletion transformants using the wheat endophytic strain T. simmonsii T137 as host. Results confirmed that hex1 gene is involved in the prevention of cytoplasmatic bleeding, and also has a role in fungal growth and biocontrol potential against phytopathogenic fungi and oomycetes. The involvement of hex1 in the fungal response to osmotic and oxidative stresses is conditioned by the type of stress and by the nutrient richness of the culture medium. The hex1 deletion also affected the interaction with wheat, but did not affect the plant protective effect of T137 against water stress. Overall, this study shows the implication of HEX1 in a wide range of biological processes necessary for T. simmonsii to deploy its abilities to be used as an agriculturally beneficial fungus.
Woronin 体是 Pezizomycotina 真菌中独特的细胞器,可使菌丝分隔并防止机械损伤后的细胞质出血。多项研究表明,过氧异构体蛋白 HEX1(Woronin 体的主要成分)与其他生物过程(如菌丝生长、渗透胁迫耐受性和致病性)有关。毛霉属是对植物有益的多用途生物控制剂,蛋白质组和转录组研究表明,在真菌细胞壁和植物聚合物存在的情况下生长时,HEX1 及其相应基因的比例过高。为了进一步研究 hex1 参与毛霉生物学的情况,我们以小麦内生菌株 T. simmonsii T137 为宿主,产生了 hex1 缺失转化子。结果证实,hex1 基因参与防止细胞质出血,还在真菌生长和对植物病原真菌和卵菌的生物控制潜力方面发挥作用。hex1 参与真菌对渗透胁迫和氧化胁迫的反应受胁迫类型和培养基营养丰富程度的影响。hex1 基因缺失也影响了与小麦的相互作用,但并不影响 T137 对水分胁迫的植物保护作用。总之,这项研究表明了 HEX1 在西蒙氏菌作为一种对农业有益的真菌所需的各种生物过程中的作用。
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引用次数: 0
The gut core microbial species Bifidobacterium longum: Colonization, mechanisms, and health benefits 肠道核心微生物物种长双歧杆菌:定植、机制和健康益处
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-07 DOI: 10.1016/j.micres.2024.127966
Yue Xiao , Lijuan Huang , Jianxin Zhao , Wei Chen , Wenwei Lu
Bifidobacterium longum (B. longum) is a species of the core microbiome in the human gut, whose abundance is closely associated with host age and health status. B. longum has been shown to modulate host gut microecology and have the potential to alleviate various diseases. Comprehensive understanding on the colonization mechanism of B. longum and mechanism of the host-B. longum interactions, can provide us possibility to prevent and treat human diseases through B. longum-directed strategies. In this review, we summarized the gut colonization characteristics of B. longum, discussed the diet factors that have ability/potential to enrich indigenous and/or ingested B. longum strains, and reviewed the intervention mechanisms of B. longum in multiple diseases. The key findings are as follows: First, B. longum has specialized colonization mechanisms, like a wide carbohydrate utilization spectrum that allows it to adapt to the host's diet, species-level conserved genes encoding bile salt hydrolase (BSHs), and appropriate bacterial surface structures. Second, dietary intervention (e.g., anthocyanins) could effectively improve the gut colonization of B. longum, demonstrating the feasibility of diet-tuned strain colonization. Finally, we analyzed the skewed abundance of B. longum in different types of diseases and summarized the main mechanisms by which B. longum alleviates digestive (repairing the intestinal mucosal barrier by stimulating Paneth cell activity), immune (up-regulating the regulatory T cell (Treg) populations and maintaining the balance of Th1/Th2), and neurological diseases (regulating the kynurenine pathway and quinolinic acid levels in the brain through the gut-brain axis).
长双歧杆菌(B. longum)是人类肠道核心微生物组的一个物种,其丰度与宿主的年龄和健康状况密切相关。研究表明,长双歧杆菌能调节宿主肠道微生态,并具有缓解各种疾病的潜力。全面了解长春花酵母菌的定植机制以及宿主与长春花酵母菌之间的相互作用机制,可为通过长春花酵母菌导向策略预防和治疗人类疾病提供可能。在这篇综述中,我们总结了长春花酵母菌的肠道定植特征,讨论了有能力/有潜力富集本地和/或摄入的长春花酵母菌菌株的饮食因素,并回顾了长春花酵母菌在多种疾病中的干预机制。主要发现如下:首先,长春芽孢杆菌具有专门的定植机制,如广泛的碳水化合物利用谱使其能够适应宿主的饮食、编码胆盐水解酶(BSHs)的物种级保守基因以及适当的细菌表面结构。其次,膳食干预(如花青素)可有效改善龙胆球菌的肠道定植,证明了膳食调整菌株定植的可行性。最后,我们分析了长春花酵母菌在不同类型疾病中的偏态丰度,并总结了长春花酵母菌缓解消化系统疾病(通过刺激Paneth细胞活性修复肠粘膜屏障)、免疫系统疾病(上调调节性T细胞(Treg)数量并维持Th1/Th2平衡)和神经系统疾病(通过肠脑轴调节脑内犬尿氨酸途径和喹啉酸水平)的主要机制。
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引用次数: 0
Extracellular Hsp90 of Candida albicans contributes to the virulence of the pathogen by activating the NF-κB signaling pathway and inducing macrophage pyroptosis 白色念珠菌的胞外 Hsp90 通过激活 NF-κB 信号通路和诱导巨噬细胞热毒症,增强了病原体的毒力。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-05 DOI: 10.1016/j.micres.2024.127964
Ting Fang , Juan Xiong , Xin Huang , Xinyu Fang , Xuqing Shen , Yuanying Jiang , Hui Lu
Strategies aimed at targeting fungal extracellular heat shock protein 90 (eHsp90) using vaccines and antibodies have demonstrated encouraging potential in the prevention and management of invasive fungal diseases (IFDs). However, the precise underlying mechanism by which eHsp90 contributes to the heightened virulence of Candida albicans (C. albicans) remains an enigma, awaiting further elucidation. In our current research, we have found that the 47-kDa fragment of C. albicans Hsp90 (CaHsp90), which serves as the primary antigenic determinant, is not degraded within C. albicans cells. Moreover, we have discovered that extracellular CaHsp90 (eCaHsp90) is derived from the components of lysed C. albicans cells. We also generated recombinant CaHsp90 in Escherichia coli, and found that eCaHsp90 spreads beyond the initial C. albicans colonization site, thereby enhancing the overall virulence of the organism. Our results further clarify that eCaHsp90 activates the nuclear factor kappa-B (NF-κB) signaling pathway and upregulates the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3). This upregulation results in the activation of Gasdermin D (GSDMD) and subsequent macrophage pyroptosis, ultimately increasing the virulence of C. albicans. This study provides valuable insights into the mechanism by which eCaHsp90 contributes to the virulence of C. albicans, offering a pharmacological basis for antifungal strategies targeting fungal eHsp90.
利用疫苗和抗体靶向真菌细胞外热休克蛋白 90(eHsp90)的策略在预防和治疗侵袭性真菌疾病(IFDs)方面已显示出令人鼓舞的潜力。然而,eHsp90 导致白念珠菌(C. albicans)毒力增强的确切内在机制仍是一个谜,有待进一步阐明。在目前的研究中,我们发现作为主要抗原决定因子的白念珠菌 Hsp90(CaHsp90)47-kDa 片段在白念珠菌细胞内不会降解。此外,我们还发现细胞外 CaHsp90(eCaHsp90)来自裂解的白僵菌细胞成分。我们还在大肠杆菌中生成了重组 CaHsp90,并发现 eCaHsp90 会扩散到白僵菌最初的定植点之外,从而增强了该生物的整体毒力。我们的研究结果进一步阐明,eCaHsp90 可激活核因子卡巴-B(NF-κB)信号通路,并上调含 NACHT、LRR 和 PYD 结构域的蛋白 3(NLRP3)的表达。这种上调会导致加斯德敏 D(GSDMD)的活化和随后的巨噬细胞脓毒症,最终增强白僵菌的毒力。这项研究为了解 eCaHsp90 促进白僵菌毒力的机制提供了宝贵的见解,为针对真菌 eHsp90 的抗真菌策略提供了药理学基础。
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引用次数: 0
Cell-Penetrating Peptides in infection and immunization 细胞穿透肽在感染和免疫中的应用。
IF 6.1 1区 生物学 Q1 MICROBIOLOGY Pub Date : 2024-11-05 DOI: 10.1016/j.micres.2024.127963
Yongliang Du , Yan Xiong , Zhou Sha , Dong Guo , Beibei Fu , Xiaoyuan Lin , Haibo Wu
Bacteria and viruses pose significant threats to human health, as drug molecules and therapeutic agents are often hindered by cell membranes and tissue barriers from reaching intracellular targets. Cell-penetrating peptides (CPPs), composed of 5–30 amino acids, function as molecular shuttles that facilitate the translocation of therapeutic agents across biological barriers. Despite their therapeutic potential, CPPs exhibit limitations, such as insufficient cell specificity, low in vivo stability, reduced delivery efficiency, and limited tolerance under serum conditions. However, intelligent design and chemical modifications can enhance their cell penetration, stability, and selectivity. These advancements could significantly improve CPP-based drug delivery strategies, facilitating both infection treatment and immunization against bacterial and viral diseases. This review provides an overview of the applications of CPPs in various infections and immune diseases, summarizing their mechanisms and the challenges encountered during their application.
细菌和病毒对人类健康构成重大威胁,因为药物分子和治疗剂往往受到细胞膜和组织屏障的阻碍,无法到达细胞内靶点。细胞穿透肽(CPPs)由 5-30 个氨基酸组成,具有分子穿梭器的功能,可促进治疗药物穿越生物屏障。尽管具有治疗潜力,但 CPPs 也有其局限性,如细胞特异性不足、体内稳定性低、递送效率降低以及在血清条件下的耐受性有限。然而,智能设计和化学修饰可以增强其细胞穿透性、稳定性和选择性。这些进步可以大大改善基于 CPP 的给药策略,促进感染治疗和针对细菌和病毒疾病的免疫。本综述概述了 CPPs 在各种感染和免疫疾病中的应用,总结了它们的作用机制和应用过程中遇到的挑战。
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Microbiological research
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