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抗真菌肽对真菌作用机制研究进展 总被引:5,自引:0,他引:5
20 世纪 90 年代初, Iijima 等从麻蝇幼虫血淋巴分离出一种具有抗真菌活性、能抑制 C.albicans 生长的蛋白质 . 到目前为止,已发现 150 多种肽具有抗真菌的特性,随着被发现的抗真菌肽数目不断增多,人们对抗真菌肽的抗真菌机理也进行了大量的研究,抗真菌肽对真菌的作用方式主要有:阻止、破坏真菌细胞壁的合成;与膜作用,在质膜上形成孔洞,使重要的内容物外泄;与真菌细胞内线粒体、核酸大分子等重要细胞器相互作用;最终导致真菌的死亡 . 相似文献
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烟曲霉(Aspergillus fumigatus)是导致曲霉病的最常见病原体,唑类药物如伊曲康唑、泊沙康唑和伏立康唑是治疗曲霉病的一线药物。近年来,随着唑类药物的广泛使用,全球范围内的烟曲霉耐药率迅速增加,严重威胁患者的生命安全[1]。烟曲霉唑类耐药机制有多种,其中最常见的是cyp51A基因突变导致蛋白质构象的变化[2-3]。常见的耐药检测方法主要包括基于分离培养的耐药检测、质谱、NGS技术和PCR技术。烟曲霉耐药机制的研究及耐药菌的鉴定对指导临床用药具有重要意义。文章对临床或文献报道的烟曲霉唑类耐药机制及检测方法进行总结。 相似文献
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真菌鞘脂代谢及其与抗真菌药物关系研究进展 总被引:1,自引:0,他引:1
鞘脂是真核细胞中普遍存在的成分,它在真核细胞的胞吞、胞饮、信号转导、细胞的生长、凋亡、分化、衰老等过程中起着非常重要的作用.该文论述了真菌鞘脂代谢的途径及参与其合成的相关酶和基因,并比较了真菌与哺乳动物鞘脂代谢途径的不同,旨在为研究新型无公害抗真菌药物提供理论依据. 相似文献
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由于唑类药物长期使用,真菌耐药性及其交叉耐药现象不断出现,对临床治疗具有重要威胁。近年来提出新型抗真菌药物的新靶点,并研发出具有高活性强、强疗效的抗真菌药物。本研究对近年来新型抗真菌药的种类、结构和特点进行阐述,并介绍不同型药物对真菌的细胞壁、细胞膜、蛋白质合成、呼吸链等作用新靶点和作用机制的研究进展。 相似文献
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<正>近年来,随着糖皮质激素、肿瘤化疗药、抗菌药物及免疫抑制剂等的广泛使用,侵袭性真菌感染(invasive fungal infection, IFI)的发病率逐年上升,死亡率已超过50%[1]。高死亡率加上治疗药物选择的局限性导致全世界每年都有超过150万人死亡[2]。临床上将唑类、棘白菌素类、多烯类和嘧啶类作为治疗和预防IFI的主要药物。在唑类药物中,三唑类药物是最常用的系统性抗真菌药物,与多烯类相比,三唑类药物具有更好的耐受性和不良反应少的优势[3]。 相似文献
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Molecular mechanisms of azole resistance in fungi 总被引:11,自引:0,他引:11
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嗜角蛋白真菌感染能引起人体皮肤浅表和深部疾病,其感染发生率近年来呈逐年增加趋势。广谱抗生素是目前广泛用于治疗嗜角蛋白真菌感染的药物种类之一,但由于可选择药物种类有限,因此多数嗜角蛋白真菌感染患者存在长期、过度使用单一广谱抗生素的情形,这可能直接或间接导致嗜角蛋白真菌耐药性形成,严重制约嗜角蛋白真菌感染疾病治疗效果,从而加重嗜角蛋白真菌感染疾病的传染风险,成为影响全球公共卫生健康的重大威胁因素之一。本文就嗜角蛋白真菌致病类型、常用药物、药物作用机理、耐药性形成及影响因素方面的研究进展进行综述,并提出了嗜角蛋白真菌耐药性未来的研究内容及方向。以期为嗜角蛋白真菌感染治疗、真菌耐药性形成机理及预防真菌感染提供新的思路和参考。 相似文献
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Elisabete Ricardo Sofia Costa-de-Oliveira Ana Silva Dias José Guerra Acácio Gonçalves Rodrigues & Cidália Pina-Vaz 《FEMS yeast research》2009,9(4):618-625
Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida . The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 μg mL−1 ); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1 , CDR2 , MDR1 , encoding for efflux pumps, and ERG11 , encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly ( P >0.05), probably acting as a Cdrp blocker. 相似文献
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The in vitro activity of seven azole compounds viz clotrimozole, isoconazole, bifanazole, fluconazole oxyconazole, Bay n 7133 and Bay L 9139 was investigated against 47 clinical isolates of pathogenic non-dermatophytic filamentous fungi and dermatophytic fungi. The isolates included Hendersonula toruloidea-26, Scytalidium hyalinium-5, Scytalidium japonicum-1, Trichophyton rubrum-5, Trichophyton tonsurans-3, Trichophyton mentagrophytes var. mentagrophytes-4, Epidemophyton floccosum-2, Microporum gypseum-2 isolates. The drugs were significantly more active against the dermatophytes (MIC range 0.025–1.56 g/ml) than non-dermatophytes (MIC range 0.39–6.25 g/ml). Isoconazole showed more activity than the rest of the azole compound tested. Clotrimazole, fluconazole, oxyconazole, bifonazole were comparable in their inhibitory activity against both dermatophytes and non-dermatophytes. The azole derivatives, Bay n 7133 and Bay L 9139 showed higher MIC range i.e. gave a range of 0.39–1.56 g/ml for dermatophytes and 1.56–6.25 g/ml for non-dermatophytic filamentous fungi. The minimal fungicidal concentration (MFC) of all the drugs tested were mostly within 2–8 times their MIC values. 相似文献
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Espinel-Ingroff A 《Revista iberoamericana de micología》2008,25(2):101-106
Failure to respond to antifungal therapy could be due to in vitro resistance (intrinsic or developed during therapy) or clinical resistance; the latter is associated with numerous factors related to the host, the antifungal agent, or the infecting isolate. Recently, a susceptible MIC breakpoint ( < or =2 microg/ml) was designed for Candida spp. to all three available echinocandins, anidulafungin (Pfizer), caspofungin (Merck) and micafungin (Astellas) and treatment failures have been associated with MICs > 2 microg/ml. In some of these cases, clinical failure was associated with the genetic mutations described below. Azole and flucytosine breakpoints, and the echinocandin susceptible breakpoint, are useful when isolates are tested by CLSI standardized methods; breakpoints are also available by the EUCAST method. More recently, in vitro resistant MIC breakpoints have been assigned for filamentous fungi (moulds) vs. five antifungal agents, but these categories are not based on correlations of in vitro with in vivo response to therapy. However, itraconazole (Janssen), amphotericin B (Bristol-Myers) and voriconazole (Pfizer) clinical failures in aspergillosis have been correlated with MICs > 2 microg/ml. This article provides a review of reported resistance molecular mechanisms to antifungal agents since 2005; previous related reviews are also listed. 相似文献
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Vanden Bossche H 《Revista iberoamericana de micología》1997,14(2):44-49
The many drugs that are available at present to treat fungal infections can be divided into four broad groups on the basis of their mechanism of action. These antifungal agents either inhibit macromolecule synthesis (flucytosine), impair membrane barrier function (polyenes), inhibit ergosterol synthesis (allylamines, thiocarbamates, azole derivatives, morpholines), or interact with microtubules (griseofulvin). Drug resistance has been identified as the major cause of treatment failure among patients treated with flucytosine. A lesion in the UMP-pyrophosphorylase is the most frequent clinical determinant of resistance to 5FC in Candida albicans. Despite extensive use of polyene antibiotics for more than 30 years, emergence of acquired resistance seems not be a significant clinical problem. Polyene-resistant Candida isolates have a marked decrease in their ergosterol content. Acquired resistance to allylamines has not been reported from human pathogens, but, resistant phenotypes have been reported for variants of Saccharomyces cerevisiae and of Ustilago maydis. Tolerance to morpholines is seldom found. Intrinsic resistance to griseofulvin is due to the absence of a prolonged energy-dependent transport system for this antibiotic. Resistance to azole antifungal agents is known to be exceptional, although it does now appear to be increasing in importance in some groups of patients infected with e.g. Candida spp., Histoplasma capsulatum or Cryptococcus neoformans. For example, resistance to fluconazole is emerging in C. albicans, the major agent of oro-pharyngeal candidosis in AIDS patients, after long-term suppressive therapy. In the majority of cases, primary and secondary resistance to fluconazole and cross-resistance to other azole antifungal agents seems to originate from decreased intracellular accumulation of the azoles, which may result from reduced uptake or increased efflux of the molecules. In most C. albicans isolates the decreased intracellular levels can be correlated with enhanced azole efflux, a phenomenon linked to an increase in the amounts of mRNA of a C. albicans ABC transporter gene CDR1 and of a gene (BEN(r) or CaMDR) coding for a transporter belonging to the class of major facilitator multidrug efflux transporters. Not only fluconazole, ketoconazole and itraconazole are substrates for CDR1, terbinafine and amorolfine have also been established as substrates, BEN(r) overexpression only accounts for fluconazole resistance. Other sources of resistance: changes in membrane sterols and phospholipids, altered or overproduced target enzyme(s) and compensatory mutations in the Delta5,6-desaturase. 相似文献
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目的通过对中国侵袭性真菌监测网(CHIF-NET)2013年中国48家综合医院收集的1 562株酵母菌进行流行病学分布及唑类耐药性分析,为临床侵袭性酵母菌的唑类用药提供数据基础。方法收集2013年中国侵袭性真菌监测网48家医院共1 562株酵母菌菌株及其原始信息,采用基质辅助激光解析电离飞行时间质谱(MALDI-TO MS,法国生物梅里埃公司)结合核糖体DNA测序明确菌种鉴定;根据美国临床实验室标准化协会(CLSI)M44-A2纸片扩散法检测菌株对氟康唑及伏立康唑的敏感性。结果本研究共分离出酵母菌1 562株,其中白念珠菌分离率最高(38.4%),其次为近平滑念珠菌复合体(18.4%)、热带念珠菌(16.4%)、光滑念珠菌复合体(9.4%)及其他少见菌种(<6.4%);患者性别中男性占比(60.7%)高于女性(38.9%);患者年龄中,65岁以上年龄段患者最多(34.2%),其次为50~65岁(30.6%)、15~49岁(29.9%)和0~14岁患者(<1.9%);标本来源中以血液标本(46.4%)为主,其次为腹水(10.2%)、导管(9.2%)及引流液(8.5%)、分泌物(5.2%),其他标本类型均较少(<4.7%)。住院患者分离率(93%)显著高于门急诊患者(7%);科室类型中以外科患者(33.8%)为主,其次为重症监护病房(ICU)患者(27.5%)、内科患者(20.5%)及其他病房(<18.2%);药敏结果显示,白念珠菌及近平滑念珠菌复合体对氟康唑及伏立康唑敏感性均较高(>94%),热带念珠菌对氟康唑及伏立康交叉耐药率最高(21.9%),光滑念珠菌复合体交叉耐药率次之(15%),其次为季也蒙念珠菌(8.1%)和菌膜念珠菌(4.3%)。结论应持续加强中国地区侵袭性酵母菌监测,在使用抗菌药物过程中,合理控制其用量,防止耐药率的上升。 相似文献
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近年来,致病性念珠菌感染引起的侵袭性念珠菌病患者人数逐年增多。白念珠菌仍是引起感染的主要致病菌,但是由非白念念珠菌引起的感染比例显著升高。致病性念珠菌对常见抗真菌药物的耐药现象呈上升趋势,这是导致临床治疗其所致的侵袭性感染失败的重要原因之一。本文就致病性念珠菌耐药性的流行病学以及其耐药机制方面的研究进展进行了介绍。 相似文献
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Steve Kett Ayush Pathak Stefano Turillazzi Duccio Cavalieri Massimiliano Marvasi 《Proceedings. Biological sciences / The Royal Society》2021,288(1944)
Arthropods can produce a wide range of antifungal compounds, including specialist proteins, cuticular products, venoms and haemolymphs. In spite of this, many arthropod taxa, particularly eusocial insects, make use of additional antifungal compounds derived from their mutualistic association with microbes. Because multiple taxa have evolved such mutualisms, it must be assumed that, under certain ecological circumstances, natural selection has favoured them over those relying upon endogenous antifungal compound production. Further, such associations have been shown to persist versus specific pathogenic fungal antagonists for more than 50 million years, suggesting that compounds employed have retained efficacy in spite of the pathogens'' capacity to develop resistance. We provide a brief overview of antifungal compounds in the arthropods’ armoury, proposing a conceptual model to suggest why their use remains so successful. Fundamental concepts embedded within such a model may suggest strategies by which to reduce the rise of antifungal resistance within the clinical milieu. 相似文献