马尔尼菲青霉的分子生物学研究进展

马尔尼菲青霉是一种主要累及免疫受损患者的条件致病性双相真菌,近年来随着HIV感染的增多,马尔尼菲青霉病发病率呈现逐年上升的趋势。国内外学者对马尔尼菲青霉及其致病机制进行了大量的研究,尤其是分子生物学方法的应用,使人们对马尔尼菲青霉的真菌学特点和马尔尼菲青霉病的发病机制有了更深入的了解,使早期诊疗成为可能。该文主要从分子流行病学、分子遗传学和分子生物学诊断方面对马尔尼菲青霉进行综述。     

耳念珠菌的流行病学和生物学研究进展

耳念珠菌Candida auris已成为引起严重院里感染的新兴病原真菌。自2009年第一次报道以来,耳念珠菌在全球迅速传播并导致几次院内感染的暴发。与念珠菌属其他成员相比,耳念珠菌具有诸多特点,比如多重耐药、鉴别困难、死亡率高、易在医院内传播等。关于耳念珠菌的生物学和致病性研究越来越多,我们对耳念珠菌的认识也逐渐增强,本综述详细地介绍了耳念珠菌全球感染的流行病学以及该病原真菌的基本生物学特征,并对其毒力和耐药机制研究进展进行汇总,对未来关于耳念珠菌研究的前景进行了展望。     

双间柱顶孢的研究进展

双间柱顶孢是一种暗色真菌,能感染植物和人类。主要存在于热带、亚热带地区。世界各地均有散在报道,泰国的感染最高,但我国很少有报道。为进一步认识该菌,现就双间柱顶孢的分类和命名学的研究进展、流行病学现状、形态特点、生物化学、致病性及治疗等情况进行综述。     

我国临床新现的条件致病真菌感染

机会性真菌的感染近年不断增多,出现的新菌种也随之增多。尤其是近年不断出现少见的机会性真菌感染,包括酵母和酵母样真菌、暗色孢科的腐生菌、地域性流行的少见双相真菌感染及一些罕见真菌感染等。由于此类真菌引起的感染难于诊断并且难鉴定到属,流行病学较难解释,且一些菌对抗真菌药物治疗抵抗,故所引起的感染危害更大。应引起真菌工作者的高度重视。     

马尔尼菲青霉的研究现状

本文较系统地介绍了目前国内外有关马尔尼菲青霉(Penicillium marneffei)的研究概况。由于包括艾滋病在内的各种获得性免疫缺乏症易感人群数量的扩大,以及在东南亚及中国南部等马尔尼菲青霉疫源地的经济发展和国际人员交流日益增大的情况下,使这个条件性高致病性真菌感染的疫情有可能出现更大范围的扩散。目前,全球艾滋病患者的马尔尼菲青霉条件性感染已成为判断HIV感染的临床征象,其在HIV感染者中的发病率高达10%～25%左右。所以,有必要对这种区域性高致病性真菌病原和其条件性感染病症进行全面的研究和制定系统的防治措施。现从马尔尼菲青霉的菌学特点、双相形态转换的基因特性、临床流行病学、分子生物学菌种鉴定及临床诊治等方面进行扼要阐述,同时,也将介绍最近相关的研究方向。     

病原真菌生态学研究现状及方法

通过形态学、生理生化学及分子生物学等方法鉴定由自然界分离的真菌菌种,构建系统发生树,了解菌种间亲缘关系,评估种间和种内的进化规律,了解真菌与其所处环境的相互关系,是真菌生态学的主要研究目的之一。本文就真菌与自然界和动物宿主的相互关系,环境中真菌的分离和鉴定方法及系统发生学研究及现状进行综述,以期了解致病真菌的生存环境、种类发生、感染途径等,达到尽早控制感染源、探讨致病性及防治疾病传播的目的。     

毛霉菌病研究进展

毛霉菌病是由毛霉目真菌引起的一类条件致病性真菌病,可引起易感人群鼻、脑、胃肠道、皮肤等多部位的感染。近年来该病的发病率渐有上升趋势。国内外对该病的研究也有了一些新的进展。本文对毛霉菌病的流行病学、发病机制、临床表现及治疗方面进行综述。     

77例人类免疫缺陷病毒感染者临床特征分析

目的 分析人类免疫缺陷病毒(HIV)感染者的临床特点及其意义。方法 用微粒酶免疫试验和蛋白质印迹法对HIV感染者的血清进行HIV抗体初筛和确认,并对感染者的流行病学、机会性感染及免疫学特点进行分析。结果 在1998~2006年期间,我院共发现77例HIV感染者,其中上海户籍患者占了50.7%,男、女比例为2.85∶1,年龄以30~49岁为主,传播途径中以性传播最常见(40.3%)。早期症状常被忽略,以消化道及肺部真菌、假单胞菌感染,性传播疾病,病毒性肝炎,皮损等就诊于各科室。多重或多部位的机会性感染可见于大多数临床已发病患者。结论 HIV感染的及时诊断,对感染者的治疗、机会性感染的预防以及减少传播具有重要的意义。     

皮肤真菌微生态研究进展

随着近年来分子学技术的发展,高通量测序和宏基因组学技术为研究人体皮肤微生态提供了可能。皮肤微生态的变化与银屑病、特应性皮炎、痤疮和慢性伤口等多种炎症性和感染性疾病的发生和发展相关。真菌成分在皮肤中含量远低于细菌,但会影响很多皮肤疾病和机会性感染的发生,因而皮肤微生态中真菌的构成开始逐渐引起人们重视。本文将就近年皮肤真菌微生态研究方法学以及其与皮肤疾病的关系的研究进展进行综述。     

人兽共患真菌病的现状

人兽共患真菌病是由真菌引起的人和动物的感染性疾病。近年来的研究发现一些原本被认为是非致病或条件致病性的真菌,如曲霉、隐球菌、组织胞浆菌、马尔尼菲青霉等引起的人兽共患病不断增加,严重地威胁着人和动物的健康。本文主要介绍了皮肤、皮下组织及深部感染3类人兽共患真菌病的病原学及流行病学特征,以阐明预防、控制人兽共患病发生的重要意义。     

念珠菌病的临床研究进展

念珠菌病是由念珠菌属的某些种群引起的条件致病真菌感染,是人类真菌感染性疾病中最多见的疾病。临床上分为浅部皮肤黏膜念珠菌病和深部念珠菌病（亦称系统性念珠菌病）。近年来深部念珠菌病的发病率有上升趋势,该病涉及临床各科室,危害性大,病死率高,是临床研究的热点。现复习近年国内外文献,就其致病念珠菌的动态流行病学、分子流行病学以及该病的实验室诊断进展及防治现状加以简要的介绍。     

651株深部真菌感染菌种分布及耐药性分析

目的了解真菌耐药性变化趋势,探讨预防措施。方法对疑为深部真菌感染患者采样,用沙保罗培养基进行真菌分离,用ATB鉴定卡作菌种鉴定,用ATBFUNGUS板进行药敏试验。结果真菌感染中以白色假丝酵母菌感染为主,占57.6%。真菌对两性霉素-B、5-氟胞嘧啶保持较高的体外抗真菌活性,敏感率分别为94.99%和98.99%。结论深部真菌感染主要由白色假丝酵母菌、热带假丝酵母菌引起,对两性霉素-B、5-氟胞嘧啶保持较高的体外活性,两者仍是治疗真菌的有效药物。     

Generation of IL-23 producing dendritic cells (DCs) by airborne fungi regulates fungal pathogenicity via the induction of T(H)-17 responses

Interleukin-17 (IL-17) producing T helper cells (T(H)-17) comprise a newly recognized T cell subset with an emerging role in adaptive immunity to a variety of fungi. Whether different airborne fungi trigger a common signaling pathway for T(H)-17 induction, and whether this ability is related to the inherent pathogenic behavior of each fungus is currently unknown. Here we show that, as opposed to primary pathogenic fungi (Histoplasma capsulatum), opportunistic fungal pathogens (Aspergillus and Rhizopus) trigger a common innate sensing pathway in human dendritic cells (DCs) that results in robust production of IL-23 and drives T(H)-17 responses. This response requires activation of dectin-1 by the fungal cell wall polysaccharide b-glucan that is selectively exposed during the invasive growth of opportunistic fungi. Notably, unmasking of b-glucan in the cell wall of a mutant of Histoplasma not only abrogates the pathogenicity of this fungus, but also triggers the induction of IL-23 producing DCs. Thus, b-glucan exposure in the fungal cell wall is essential for the induction of IL-23/T(H)-17 axis and may represent a key factor that regulates protective immunity to opportunistic but not pathogenic fungi.     

我国重要病原性真菌的耐药性研究现状

近年来,病原性真菌的耐药现象越来越多,呈逐年上升趋势,且所致侵袭性感染已成为目前临床上患者死亡的重要原因之一。本文就我国在耐药性真菌的判断、流行病学、耐药机制及其防治等方面的研究现状进行简单介绍。     

Epidemiology of Invasive Fungal Infections in Patients with Acquired Immunodeficiency Syndrome at a Reference Hospital for Infectious Diseases in Brazil

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20–25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.     

Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity

Candida albicans is one of the most important opportunistic pathogenic fungi. Weakening of the defense mechanisms of the host, and the ability of the microorganism to adapt to the environment prevailing in the host tissues, turn the fungus from a rather harmless saprophyte into an aggressive pathogen. The disease, candidiasis, ranges from light superficial infections to deep processes that endanger the life of the patient. In the establishment of the pathogenic process, the cell wall of C. albicans (as in other pathogenic fungi) plays an important role. It is the outer structure that protects the fungus from the host defense mechanisms and initiates the direct contact with the host cells by adhering to their surface. The wall also contains important antigens and other compounds that affect the homeostatic equilibrium of the host in favor of the parasite. In this review, we discuss our present knowledge of the structure of the cell wall of C. albicans, the synthesis of its different components, and the mechanisms involved in their organization to give rise to a coherent composite. Furthermore, special emphasis has been placed on two further aspects: how the composition and structure of C. albicans cell wall compare with those from other fungi, and establishing the role of some specific wall components in pathogenesis. From the data presented here, it becomes clear that the composition, structure and synthesis of the cell wall of C. albicans display both subtle and important differences with the wall of different saprophytic fungi, and that some of these differences are of utmost importance for its pathogenic behavior.     

Thermophillic and thermotolerant fungi isolated from the thermal effluent of nuclear power generating reactors: Dispersal of human opportunistic and veterinary pathogenic fungi

Over a period of a year, samples of water, foam, microbial mat, soil and air were obtained from areas associated with the cooling canal of a nuclear power station. The seventeen sample sites included water in the cooling canal that was thermally enriched and soil and water adjacent to, upstream, downstream and at a distance from the generator. Air samples were taken at the plant and at various disstances from the plant. Fifty-two species of thermotolerant and thermophilic fungi were isolated. Of these, eleven species are grouped as opportunistic Mucorales or opportunistic Aspergillus sp. One veterinary pathogen was also isolated (Dactylaria gallopava):The opportunistic/pathogenic fungi were found primarily in the intake bay, the discharge bay and the cooling canal. Smaller numbers were obtained at both upstream and downstream locations. Soil samples near the cooling canal reflected an enrichment of thermophilous organisms, the previously mentioned opportunistic Mucorales and Aspergillus spp. Their numbers were found to be greater than that usually encountered in a mesophilic environment. However, air and soil samples taken at various distances from the power station indicated no greater abundance of these thermophilous fungi than would be expected from a thermal enriched environment. Our results indicate that there was no significant dissemination of thermophilous fungi from the thermal enriched effluents to the adjacent environment. These findings are consistent with the results of other investigators.     

Fungal toxins as a parasitic factor responsible for the establishment of fungal infections

Although the mechanism of fungal infections, particularly that of opportunistic fungus infections, has been studied extensively, much still remains to be clarified. As is the case for certain bacterial infections, it has long been assumed by numerous investigators that some toxins, enzymes and other metabolites produced in vitro as well as in vivo by pathogenic fungi or their cellular constituents might be responsible for the establishment of fungal infections. However, there are very few papers which deal with isolation and/or characterization of pathogenic fungus-derived toxins, particularly those of high molecular weight, to sufficiently meet various criteria for toxins including etiopathological ability. Likewise, it has been speculated that certain enzymes produced by pathogenic fungi are related to the pathogenesis of infections with the fungi implicated, but no direct evidence has been provided.It is commonly held by researchers concerned with medical mycology that the lowering of specific and/or nonspecific resistance of a host to pathogenic fungi is a prerequisite for the establishment of infections, particularly opportunistic infections. However, it is also accepted that if a given fungus possesses no parasite factors (e.g. toxigenicity, invasiveness and others), it would be unable to initiate infection even when the host is in a severe immunodeficient state. This is supported by our recent studies working with Saccharomyces cerevisiae and some other so-called nonpathogenic yeasts (unpublished data). Based on these considerations, the author and his co-workers have attempted to isolate several high and low molecular weight toxins in a pure state from virulent strains of Candida albicans and Aspergillus fumigatus as opportunist. Studies have also been made on the etiopathological roles of some successfully isolated toxins in infections with the fungi implicated (46).In addition to our experimental results, general concepts in fungal toxins, particularly those related to such toxins as isolated in our laboratory are outlined. Since opportunistic fungus infections have created a global problem because of their world-wide prevalence, a sharp demarcation between the so-called pathogenic and nonpathogenic fungi has become vague. Despite this situation, two terms are conventionally used throughout this paper.The author thanks Drs. H. Yamaguchi and K. Uchida, Y. Yamamoto, T. Hiratani, and Y. Nozu for their collaboration during these studies.     

Biotyping of pathogenic fungi by the killer system and with monoclonal antibodies

Biotyping of pathogenic yeasts and hyphomycetes based on their suceptibility to selected killer yeasts and their reactivity with monoclonal antibodies are described. Both methods were used to differentiate fungi isolated from patients providing valuable epidemiological information on mycotic infections. The functional biotyping obtained with the two systems and the conventional auxenographic biocoding approaches commercially available for opportunistic yeasts are comparatively evaluated. The potential for biotyping of industrial fungal isolates is also discussed.     

生殖道念珠菌病病原真菌的调查及药敏试验

目的了解本地区生殖道念珠菌病病原真菌构成及其体外药敏试验情况。方法采用科玛嘉念珠菌显色培养基和YBC鉴定卡对患者1164份生殖道标本的致病真菌进行分离和鉴定,并用ROSCO纸片扩散法检测分离菌株对制霉菌素、酮康唑、氟康唑、伊曲康唑、咪康唑和特比萘芬的药敏情况。结果共分离9种295株念珠菌,其中自念珠菌为85．76％,近平滑念珠菌为7．46％,光滑念珠菌为3．39％,其他念珠菌为3．39％。295株念珠菌对制霉菌素、酮康唑、氟康唑、伊曲康唑、咪康唑和特比萘芬的敏感性分别为99．66％、97．29％、89．83％、72．22％、46．44％和36．61％。结论本地区生殖道念珠菌病患者致病菌分布以白念珠菌为主,体外药敏显示制霉菌素、酮康唑和氟康唑有较好的敏感性。