铁和细菌

在传染过程中铁元素起着非常重要的作用。宿主组织的内环境对其中病原菌的特性和生长的影响都与病原菌对铁的利用有关。传染过程得以发生的基本因素是病原菌侵袭力,即在宿主体内各种环境条件下病原菌成功繁殖的能力。病原性微生物必须摄取足够的铁方能在宿主体内生长繁殖,而宿主组织中可供细菌所利用的铁有时是有限的。此外,环境中铁的存在与否也是协调细菌毒力     

高等植物中铁的代谢机制

铁在高等植物的生长发育中发挥着重要作用,但随着人类的耕作及土壤的盐碱化,缺铁已成为一个世界性植物营养问题。高等植物在长期的进化过程中,形成了完善的对环境铁信号响应的体系。本文围绕植物与环境的相互作用,综述了近年来植物铁营养的吸收、转运、分配和储存的研究进展,并总结了植物中铁营养代谢调控的相关机理。     

白念珠菌铁通透酶基因CaFTH1的功能研究

[目的]白念珠菌CaFTH1是一种铁通透酶编码基因.为了研究CaFTH1对胞内铁代谢和液泡功能的影响,构建fth1△/△单基因缺失菌株和fth1△/△fet33△/△双基因缺失菌株.[方法]利用生物信息学软件对CaFTH1进行序列比对和分析;通过实时荧光定量PCR技术研究铁离子丰度对CaFTH1表达的影响;利用PCR介导的同源重组方法构建基因缺失菌株;利用原子吸收光谱方法测定基因缺失菌株胞内铁含量的变化,并对基因缺失菌株在缺铁条件和菌丝诱导条件下的生长状况进行研究;通过代谢转换实验,研究CaFTH1对细胞液泡功能的影响.[结果]序列比对结果表明白念珠菌CaFth1蛋白属于铁通透酶Ftr1超家族,与酿酒酵母液泡膜蛋白ScFth1具有最高的同源性.铁匮乏条件会诱导CaFTH1的表达,而富铁条件则会抑制其表达.白念珠菌CaFTH1的缺失会导致胞内铁含量的降低,fth1△/△突变菌株基础上CaFET33的缺失则会进一步降低胞内铁含量.在缺铁条件下,fth1△/△fet33△/△双基因缺失菌株在一定程度上表现出代谢转换能力的缺陷.另外,在某些固体菌丝诱导培养条件下,fth1△/△fet33△/△缺失菌株菌落表面形成褶皱能力显著增强;而在液体菌丝诱导条件下,则表现为增强的菌丝聚集能力.[结论]CaFTH1是一种低铁应答基因,在维持白念珠菌胞内铁离子稳态及液泡功能方面具有重要作用.CaFTH1和CaFET33基因的双缺失会对白念珠菌的菌落形态和菌丝聚集产生影响.     

希瓦氏菌铁稳态及调控的研究进展

铁元素通常以蛋白辅因子的形式参与一系列重要的生命过程,是绝大多数生命必需的营养物质。在细菌生命过程中,一方面铁短缺是必须克服的严峻挑战,另一方面铁过量又会危及生命。铁的这种二元性质要求细菌必须严格保持体内的铁稳态。当前革兰氏阴性菌铁稳态的作用模式及理解主要基于肠道细菌大肠杆菌的长期探索成果。近年来,在环境细菌中开展的相关研究揭示了革兰氏阴性菌的铁稳态机制存在出乎意料的多样性:细菌中铁稳态相关的生物途径及组成蛋白、关键调控系统的生理影响以及铁稳态与其他生物过程的相互影响等方面都显示不同菌种的生存和进化特征。本综述以希瓦氏菌中的相关发现为基础,分析总结革兰氏阴性菌铁稳态重要途径及其组成的多样性、不同途径的相互影响以及调控因子的生理影响和调控机理等方面的研究进展和未解决的问题,以期为革兰氏阴性菌铁稳态的研究提供参考。     

白念珠菌生物被膜形成的遗传调控机制

白念珠菌是人体重要的条件性致病真菌。形态的多样性和可塑性是白念珠菌典型的生物学特征,这与它的致病性、宿主适应能力以及有性生殖过程密切相关。白念珠菌生物被膜(Biofilm)是由不同形态细胞(包括酵母型、菌丝和假菌丝)以及胞外基质组成的致密结构,也是毒性和耐药性形成的重要因子。生物被膜对抗真菌药物、宿主免疫系统和环境胁迫因子等都表现出较强的抵抗力和耐受性,是临床上病原真菌感染防治的重大挑战。随着基因表达谱和遗传操作技术的发展,白念珠菌生物被膜的形成及其耐药性的获得所依赖的遗传调控通路和分子调控机制越来越清楚。主要包括MAPK和cAMP介导的信号途径以及Bcr1和Tec1等因子介导的转录调控。此外,白念珠菌生物被膜的形成与形态转换和有性生殖之间存在密切的联系。文中综述了白念珠菌生物被膜形成的遗传调控机制,重点介绍了细胞壁相关蛋白、转录因子和交配型对该过程的调控以及生物被膜的耐药机制。     

铁调素调控与铁代谢相关疾病研究进展

铁离子对所有生物来说都是必需元素。人体组织中的铁含量被精确调控,以确保体内铁始终处于正常生理水平。多种疾病可引起人体铁代谢失调,如血色病、慢性丙型肝炎和酒精性肝病等。许多分子参与了铁调控,其中铁调素是机体铁稳态的中心调控分子。研究铁调素有助于加深人们对人体铁失调分子机制的深入认识。初步讨论了铁调素调控与铁代谢相关疾病的关系,为理解铁代谢疾病提供线索和新的临床诊断和治疗依据。     

转录因子在白念珠菌自噬过程中的调控机制CSCD

自噬是细胞内主要的降解途径之一,是一个高度保守的动态过程,对于真核细胞的适应、分化和发育具有重要作用,自噬在白念珠菌中影响着菌株的代谢和毒力,可增强菌体的存活能力。自噬调节失衡与多种疾病相关,需在多个水平受到精确调控,以维持细胞内稳态平衡。白念珠菌的毒力致病与自噬过程中关键转录因子的异常表达调控密切相关。该文主要概括了自噬的主要阶段及相关机制,并说明自噬过程中主要转录因子可能的作用机制,以了解白念珠菌自噬中的转录调控机制,为白念珠菌未来的治疗提供新的方向。     

施氏假单胞菌A1501铁吸收调节蛋白Fur的表达特性与功能鉴定

铁是细胞生理代谢的重要金属元素,是多种氧化还原酶类、过氧化物酶类的重要组成部分。革兰氏阴性菌中,胞内铁转运、储存和利用主要由铁吸收调节蛋白Fur（ferric uptake regulator）调控。水稻根际联合固氮菌——施氏假单胞菌（Pseudomonas stutzeri）A1501基因组中含有一个fur同源基因,但其具体功能尚不清楚。比较了A1501中fur基因及其编码蛋白的序列特征,并通过实时荧光定量PCR（real-time quantitative,qRT-PCR）和Western blotting杂交方法测定了fur基因和Fur蛋白的表达特性,结果发现fur基因表达水平与环境中铁浓度呈负相关,在铁限制条件下高表达,铁过量条件下表达受抑制。构建了fur基因突变株和功能回补株,表型测定发现fur突变影响了A1501的碳源代谢谱,并导致A1501对过氧化氢胁迫敏感。胞内铁含量测定表明,fur突变株内的铁含量为野生型的1.3倍,进一步qRT-PCR测定表明fur突变影响了铁离子转运系统及过氧化物酶编码基因的表达。研究结果为解析根际微生物胞内铁平衡调节及根际环境适应机制奠定了理论基础。     

白念珠菌Ras/cAMP/P KA途径研究进展

白念珠菌引起的真菌感染严重威胁着人类健康。Ras/cAMP/PKA途径在白念珠菌菌丝发育、生物被膜形成、有性生殖以及耐药性中起着重要的调控作用,该通路由GTPases(Ras1和Ras2)、腺苷环化酶(Cyr1)、cAMP水解酶(Pde1和Pde2)以及PKA激酶(包括催化亚基Tpk1和Tpk2,调节亚基Bcy1)构成。环境因子通过Ras/cAMP/PKA途径调控下游转录因子,进而调节白念珠菌多种生物学行为。文中综述了近年来白念珠菌Ras/cAMP/PKA信号通路感应胞外环境因子和调控细胞行为等方面的研究进展。     

微生物铁载体运输系统

铁是大多数生物生长所必需的元素,在生命活动中占有极其重要的地位.尽管自然界中铁元素含量丰富,但是大多敬好氧生物包括微生物都面临着铁缺乏的问题,铁载体运输系统是微生物获得铁元素的重要途径.本文就铁载体运输系统的组成、调控机制及当前微生物中的铁载体运输系统的进展作以综述.     

Effect of iron concentration on siderophore synthesis and pigment production by Candida albicans

Twelve strains of Candida albicans were grown in defined medium which had been deferrated by ion-exchange chromatography and then supplemented with FeCl3 to give iron concentrations ranging from 0.026 microM (growth-limiting) to 0.8 microM (excess). All of the strains secreted hydroxamate-type siderophores; phenolate siderophores were not detected. Isolates of C. lusitaniae, C. glabrata and C. parapsilosis also secreted hydroxamate but not phenolate-type iron chelators. Siderophore synthesis by C. albicans was maximal during growth in 0.026-0.2 microM iron. These low concentrations of iron also induced the synthesis of a green pigment, with maximal production at 0.026 microM. The pigment could be partially separated from hydroxamate siderophore activity on a column of Sephadex G-10 indicating that it probably does not function as an iron chelator.     

Effect of iron on fluconazole activity against Candida albicans in presence of human serum or monocyte-derived macrophages

Human serum, transferrin, and apotransferrin are known to profoundly inhibit the growth of Candida albicans by iron deprivation. On the other hand, iron overload (iron saturated transferrin) is a serious risk factor for candidiasis in newborn and in leukemic patients. We tested the efficacy of fluconazole and the previously demonstrated synergy of fluconazole and effector cells against C. albicans under iron overload conditions where efficacy might be diminished. We confirm that exogenous iron completely reversed the inhibitory effect of human serum and report that the efficacy of fluconazole against C. albicans was not significantly compromised in a 24 h assay system. Although exogenous iron inhibited fungistatic activity of monocyte-derived macrophages, it did not interfere with the synergistic candidacidal activity of fluconazole and monocyte-derived macrophages. In 72 h assays, where fluconazole had candidacidal activity, exogenous iron did not compromise efficacy of fluconazole, and fluconazole activity was often increased. These in vitro results suggest that effectiveness of fluconazole therapy would not be compromised in iron overload situations in vivo. This revised version was published online in August 2006 with corrections to the Cover Date.     

The role of iron in Campylobacter gene regulation,metabolism and oxidative stress defense

Enteric Campylobacter species cause gastrointestinal diseases in humans. Like almost all organisms, campylobacters have an absolute requirement for iron, but are faced with variable availability of iron in the environment and host tissues. Campylobacters have developed mechanisms to scavenge sufficient iron for metabolism and growth. However, iron also participates in the formation of reactive oxygen species, and this forces pathogens to maintain intracellular iron homeostasis and to cope with oxidative stresses. The presence of two separate, but possibly overlapping iron-responsive regulatory systems, which regulate iron acquisition and oxidative stress defense, and the presence of genes encoding multiple iron acquisition and detoxification systems in Campylobacter indicate the central role that iron plays in Campylobacter gene regulation and virulence.     

Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage

To acquire iron, all species have to overcome the problems of iron insolubility and toxicity. In response to low iron availability in the environment, most fungi excrete ferric iron-specific chelators--siderophores--to mobilize this metal. Siderophore-bound iron is subsequently utilized via the reductive iron assimilatory system or uptake of the siderophore-iron complex. Furthermore, most fungi possess intracellular siderophores as iron storage compounds. Molecular analysis of siderophore biosynthesis was initiated by pioneering studies on the basidiomycete Ustilago maydis, and has progressed recently by characterization of the relevant structural and regulatory genes in the ascomycetes Aspergillus nidulans and Neurospora crassa. In addition, significant advances in the understanding of utilization of siderophore-bound iron have been made recently in the yeasts Saccharomyces cerevisiae and Candida albicans as well as in the filamentous fungus A. nidulans. The present review summarizes molecular details of fungal siderophore biosynthesis and uptake, and the regulatory mechanisms involved in control of the corresponding genes.     

Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other Alpha-proteobacteria

Perception and response to nutritional iron by bacteria is essential for viability, and for the ability to adapt to the environment. The iron response regulator (Irr) is part of a novel regulatory scheme employed by Rhizobium and other Alpha-Proteobacteria to control iron-dependent gene expression. Bradyrhizobium japonicum senses iron through the status of heme biosynthesis to regulate gene expression, thus it responds to an iron-dependent process rather than to iron directly. Irr mediates this response by interacting directly with ferrochelatase, the enzyme that catalyzes the final step in heme biosynthesis. Irr is expressed under iron limitation to both positively and negatively modulate gene expression, but degrades in response to direct binding to heme in iron-sufficient cells. Studies with Rhizobium reveal that the regulation of iron homeostasis in bacteria is more diverse than has been generally assumed.     

Candida albicans iron acquisition within the host

As a commensal and opportunistic pathogen, Candida albicans possesses a range of determinants that contribute to survival, persistence and virulence. Among this repertoire of fitness and virulence attributes are iron acquisition factors and pathways, which allow fungal cells to gain this essential mineral in the iron-poor environment of the host. The aim of this review is to present the strategies used by C. albicans to exploit host iron reservoirs and their impact on C. albicans pathogenicity. Because iron in the human host is mostly linked to host proteins, pathogens such as C. albicans must possess mechanisms to gain iron from these proteins. Here, we introduce the most important groups of human proteins, including haemoglobin, transferrin, lactoferrin and ferritin, which contain iron and that are potential iron sources for invading microorganisms. We then summarize and discuss the known and proposed strategies by which C. albicans exploits or may exploit iron from host proteins and compare these with strategies from other pathogenic microorganisms.