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Biology, diagnosis and treatment of Malassezia dermatitis in dogs and cats 犬猫马拉色菌性皮炎的生物学，诊断和治疗-2020
Clinical Consensus Guidelines of the World Association for Veterinary Dermatology 世界兽医皮肤病学会临床共识指南 Ross Bond , Daniel O. Morris, Jacques Guillot, Emmanuel J. Bensignor , David Robson, Kenneth V. Mason, Rui Kano and Peter B. Hill
翻译：唐翔 校对：王帆
Background – The genus Malassezia is comprised of a group of lipophilic yeasts that have evolved as skin commensals and opportunistic cutaneous pathogens of a variety of mammals and birds. 背景-马拉色菌属由一组亲脂性酵母菌组成，这些酵母菌进化为多种哺乳动物和鸟类的皮肤共生菌和机会性皮肤病原体。 Objectives – The objective of this document is to provide the veterinary community and other interested parties with current information on the ecology, pathophysiology, diagnosis, treatment and prevention of skin diseases associated with Malassezia yeasts in dogs and cats. 目的-本文的目的是向兽医界和其他相关方提供与犬猫马拉色菌酵母菌相关的皮肤病的生态学、病理生理学、诊断、治疗和预防的最新信息。 Methods and material – The authors served as a Guideline Panel (GP) and reviewed the literature available prior to October 2018. The GP prepared a detailed literature review and made recommendations on selected topics. The World Association of Veterinary Dermatology (WAVD) Clinical Consensus Guideline committee provided guidance and oversight for this process. The document was presented at two international meetings of veterinary dermatology societie s and one international mycology workshop; it was made available for comment on the WAVD website for a period of six months. Comments were shared with the GP electronically and responses incorporated into the final document. 方法和材料-作者作为指导小组（GP）审查了2018年10月之前的可用文献。指导小组准备了一份详细的文献综述，并就选定的专题提出了建议。世界兽医皮肤病学会（WAVD）临床共识指导委员会为这一过程提供了指导和监督。该文件在兽医皮肤病学会的两次国际会议和一次国际真菌学研讨会上提交；该文件在WAVD网站上供评论，为期六个月。以电子方式与GP交流意见，并将答复纳入最后文件。 Conclusions and clinical importance – There has been a remarkable expansion of knowledge on Malassezia yeasts and their role in animal disease, particularly since the early 1990’s. Malassezia dermatitis in dogs and cats has evolved from a disease of obscurity and controversy on its existence, to now being a routine diagnosis in general veterinary practice. Clinical signs are well recognised and diagnostic approaches are well developed. A range of topical and systemic therapies is known to be effective, especially when predisposing factors are identified and corrected. 结论和临床意义-马拉色菌酵母菌的知识及其在动物疾病中的作用有了显著的扩展，特别是自1990年初以来，犬猫马拉色菌皮炎已经从一种晦涩难懂的疾病演变现在被兽医常规诊断的疾病。临床症状得到了很好的认识，诊断方法也得到了很好的发展。众所周知，一系列局部和全身治疗是有效的，特别是当易感因素被识别和纠正时。
1 Introduction 1 引言 Scientists have been grappling with the complexity of the genus Malassezia and their associated diseases for decades. Their relevance to companion animal veterinary practitioners first became apparent in the context of canine otitis externa in the 1950’s, whereas their role in canine dermatitis was not established until more recently. Malassezia dermatitis is now recognised as a common skin disorder in canine practice, although it is encountered more occasionally in feline practice. 科学家们数十年来一直在努力研究马拉色菌属及其相关疾病的复杂性。20世纪50年代，在犬外耳炎的背景下，它们与伴侣动物兽医从业者的相关性首次显现出来，然而直到最近才确定它们在犬皮炎中的作用。马拉色菌皮炎是目前公认的一种在犬上常见的皮肤病，尽管更多在猫上偶尔发现过。
The commissioning of this review by the World Association for Veterinary Dermatology (WAVD) is timely, given the marked advances in our understanding of these lipophilic yeasts as a consequence of significant scientific endeavour, not least the sequencing of the genomes of the majority of the recognised species. Molecular biological techniques have transformed the taxonomy of the genus from two species in 1989 to 18 species at the time of publication, in the process explaining, at a stroke, many of the painstaking observations of phenotypic variation made by generations of mycologists. 考虑到我们对这些亲脂性酵母菌的理解取得了显著进展，作为重大科学努力的结果，尤其是大多数公认种属的基因组测序，世界兽医皮肤病协会 (WAVD) 委托进行综述是及时的。分子生物学技术使该属的分类学从 1989 年的两种转变为发表时的18种，在这一过程一举解释了几代真菌学家对表型变异所做的许多艰苦观察。
This is the second WAVD consensus document on superficial veterinary mycoses, following on from one for dermatophytosis.1Whilst the headline title of our review is “diagnosis and treatment”, the complexity of Malassezia dermatitis in dogs and cats requires a wider-ranging review. Unlike the dermatophytes, which visit and potentially infect the non-immune host, Malassezia yeasts are commensal organisms, forming a reservoir of potential pathogens in the stratum corneum or mucosae, that may induce disease whenever the homeostatic balance of yeast virulence, on the one hand, and host immunity, on the other, is disrupted in favour of the yeast. 这是第二篇关于浅表兽医真菌病的 WAVD 共识文件，第一篇是关于皮肤癣菌病的 WAVD 共识文件。虽然我们综述的标题是“诊断和治疗”，但犬猫马拉色菌皮炎的复杂性需要更广泛的综述。不像是皮肤癣菌可以侵袭并潜在地感染非免疫宿主，马拉色菌酵母菌是共生菌，在角质层或粘膜层中形成一个潜在病原体的储存库，当酵母菌毒力的稳态平衡和宿主免疫平衡被破坏时，就有利于酵母菌增殖而诱发疾病。
Our review includes a full description of the genus, since six of the currently recognised species have been described on dogs and cats, and six more have been described in other species encountered by veterinary practitioners. The wide range of methods used to define and quantify Malassezia yeasts on skin is assessed; rarely does one investigator use the same method as the next, but the different methods often yield diverse and conflicting data; highlighting the strengths and weaknesses of each should promote careful method selection for future studies. A basic description of molecular methods is incorporated to aid the non-specialist reader in understanding how these techniques are currently applied to yeast identification and epidemiology, and how in future they may change our diagnostic approach to the case. A discussion of current concepts of yeast virulence and host immunity is a necessary prelude to a review of immunological methods in diagnosis and therapy, and in the context of the crucial consideration of the host predisposing factors, whose recognition and correction is key to the prevention of chronically-relapsing disease. 我们的综述包括该属的完整描述，因为目前公认的6个种属已在犬和猫中描述，另外6个种属已在兽医从业者遇到的其他种属中描述。评估了用于定义和定量皮肤上马拉色菌酵母菌的广泛方法；一名研究者很少使用与下一名研究者相同的方法，但不同的方法通常产生不同和矛盾的数据；强调每种方法的优点和缺点应促进未来研究的仔细方法选择。纳入了分子方法的基本描述，以帮助非专家读者了解这些技术目前如何应用于酵母菌鉴定和流行病学，以及未来它们如何可能改变我们对该病例的诊断方法。对当前酵母菌毒力和宿主免疫概念的讨论是对诊断和治疗中免疫学方法进行综述的必要前奏，在对宿主易感因素进行关键考虑的背景下，其识别和纠正是预防慢性复发性疾病的关键。
As the title indicates, one of our principal objectives is to describe the range of clinical presentations in dogs and cats, along with a suggested approach to elucidating the role, if any, of Malassezia yeasts in each case. Our therapeutic recommendations are drawn from both a systematic review of published therapeutic studies (Section 15.2). Given the general paucity of high quality trials in this field, consensus views from the panel of authors have also been incorporated. Thus, our concluding summary of therapeutic options is a combination of evidence base and consensus of opinion. Finally, in the spirit of a “one health” approach, the zoonotic potential of these yeasts is reviewed. 如标题所示，我们的主要目的之一是描述犬和猫的临床表现范围，以及阐明马拉色菌酵母菌在每种情况下的作用（如果有的话）的建议方法。我们的治疗建议来自已发表治疗研究的系统综述（第15.2节）。鉴于该领域高质量试验的普遍缺乏，作者小组的共识观点也被纳入。因此，我们对治疗选择的总结是证据基础和共识意见的组合。最后，本着“一个健康”的精神，对这些酵母菌的人畜共患病潜力进行了综述。
2 The genus Malassezia. General properties, phylogeny, genomic studies and species of relevance to veterinary medicine 2 马拉色菌属。与兽医学相关的一般特性、系统学、基因组研究和种属 Malassezia yeasts form a well-defined and unique cluster of lipophilic fungi living almost exclusively on the skin and mucosal sites of warm-blooded vertebrates. The genus Malassezia (Baillon) is usually considered as a monophyletic taxon in the phylum Basidiomycota and subphylum Ustilaginomycotina, a highly diversified group of more than 1,500 species of plant pathogens. Molecular analysis has confirmed that the genus Malassezia is deeply rooted in the Ustilaginomycotina with a sister relationship to Ustilaginomycetes and Exobasidiomycetes. As a consequence, it was proposed that the genus should be assigned as its own class, Malasseziomycetes.During the last decade, the analysis of the genome of Malassezia yeasts has allowed a better understanding of how these fungi, whose ancestors were most probably plant or soil residents, manage to survive and develop in the cutaneous ecosystem and how they interact with other members of the cutaneous microbiota. In 2007 the first genome sequence of a Malassezia species (M. globosa) was published.A few years later, a similar analysis was performed for M. sympodialis and for M. pachydermatis. In 2015, a study reported the sequences, assemblage and annotations for the genomes of 14 Malassezia species, including multiple strains of the most relevant species in medical dermatology (M. globosa, M. sympodialis, M. restricta and M. furfur). 马拉色菌酵母菌形成了一个定义明确且独特的亲脂性真菌簇，几乎只生活在温血动物脊椎动物的皮肤和粘膜部位。马拉色菌属 (Baillon) 通常被认为是担子菌门和黑曲霉亚门中的一个单系分类群，是由1500多种植物病原菌组成的高度多样化的类群。分子分析证实，马拉色菌属深根于黑曲霉，与黑曲霉和外担子菌有姊妹关系。因此，有人提出该属应归为自己的纲——马拉色菌。在过去十年中，对马拉色菌酵母菌基因组的分析使人们更好地了解了这些真菌，其祖先最有可能是植物或土壤居民，如何在皮肤生态系统中生存和发育，以及它们如何与皮肤微生物群的其他成员相互作用。2007 年，首次发表了马拉色菌属 (球形马拉色) 的基因组序列。几年后，对合轴马拉色菌和厚皮马拉色菌进行了类似的分析。2015 年，一项研究报道了 14 种马拉色菌基因组的序列、组装和注释，包括医学皮肤病学中最相关物种的多个菌株（球形马拉色菌、合轴马拉色菌、限制马拉色菌和糠秕马拉色菌）。
The first remarkable feature of Malassezia genomes is their small size (~10 Mb), about half of the size of other known basidiomycetous fungi, with some species having less than 4,000 predicted genes.This may reflect adaptation to the limited ecological niche of the yeasts. Gene family analyses indicate that Malassezia yeasts display unique characteristics comprising (i) a low carbohydrate-degrading capacity due to reduction of glycosyl hydrolase-encoding genes; (ii) a lipid dependence for growth due to lack of a fatty acid synthase gene and (iii) a concomitant expansion of lipid hydrolysing enzymes (such as secreted lipases, phospholipases and acid sphingomyelinases) that allow Malassezia yeasts to collect and use fatty acids from the skin or mucosal surfaces of their hosts. Analysis of the genomes also revealed the presence of unique genes with unknown function and which were probably acquired through horizontal gene transfer. 马拉色菌基因组的第一个显著特征是体积小 (~10mb)，约为其他已知担子菌真菌大小的一半，一些物种的预测基因少于 4000 个。这可能反映了对酵母菌有限生态位的适应。基因家族分析表明，马拉色菌酵母菌具有独特的特性，包括 (i) 糖基水解酶编码基因的减少导致碳水化合物降解能力低下；(ii) 由于缺乏脂肪酸合成酶基因导致的生长脂质依赖性和 (iii) 伴随的脂质水解酶（如分泌型脂肪酶、磷脂酶和酸性鞘磷脂酶）扩增，使马拉色菌酵母菌从其宿主的皮肤或粘膜表面收集和使用脂肪酸。基因组分析也揭示了功能未知的独特基因的存在，这些基因可能是通过水平基因转移获得的。
The sexual form of Malassezia yeasts is still unknown. However, a region corresponding to the mating type locus (MAT) has been identified for these yeasts;6 it has been suggested that if there is an extant sexual cycle for some of them that it is more likely to be bipolar or pseudo-bipolar, with two mating types, rather than tetrapolar as in many other basidiomycetous fungi. 马拉色菌酵母菌的性形式仍不清楚。然而，这些酵母的交配型位点 (MAT) 对应的区域已被确定；有人认为，如果其中一些酵母存在现存的性周期，则更可能是双极或伪双极，具有两种交配类型，而不是像许多其他担子菌真菌中那样的四极。
On lipid-enriched media such as modified Dixon’s agar, Malassezia colonies are cream to yellowish, smooth or lightly wrinkled, glistening or dull, with the margin being either entire or lobate. Malassezia yeasts appear as small ovoid, ellipsoidal or cylindrical cells (1.5 to 6.0 µm by 3.5 to 8.0 µm). Reproduction is by budding on a broad base and from the same site at one pole (monopolar blastic development). Some Malassezia species are able to form filaments in cutaneous lesions but also in culture under specific conditions. Malassezia yeasts have a thick cell wall (~0.12 µm) whose innermost layer shows a characteristic serrated structure. 在改良 Dixon 琼脂等富含脂质的培养基上，马拉色菌菌落呈奶油色至淡黄色、光滑或轻微起皱、闪亮或无光泽，边缘或完整或呈浅裂状。马拉色菌酵母菌表现为小的卵圆形、椭圆形或圆柱形细胞 (1.5-6.0µm×3.5-8.0µm)。繁殖是通过在一个广泛的基础上和从一个极的相同地点出芽（单极急变发育）。一些马拉色菌属能够在皮肤病变中形成细丝，但在特定条件下也能在培养中形成细丝。马拉色菌酵母菌具有较厚的细胞壁 (~0.12µm)，其最内层显示出特征性的锯齿状结构。
The genus Malassezia (Baillon) was created in 1889 for a single species, M. furfur, observed in lesions of pityriasis versicolor, a common dermatological condition in humans. It took a long time to understand the lipid dependence of this kind of fungus and, as a consequence, to obtain and maintain Malassezia yeasts in culture. Conventional laboratory techniques could not be used and despite the description of numerous species, their accurate identification was not possible. In 1989, the genus Malassezia (Baillon 1889), also known under the generic name Pityrosporum proposed by Sabouraud in 1904, comprised only two taxa: M. furfur (syn. P. ovale, P. orbiculare), a lipid dependent species found on human skin and M. pachydermatis (syn. P. pachydermatis, P. canis), a species isolated from the skin of animals, especially dogs. 马拉色菌属 (Baillon) 是 1889 年为单一菌种糠秕马拉色菌创建的，在花斑糠疹（一种人类常见皮肤病）的皮肤病变中观察到。人们花了很长时间来了解这类真菌的脂质依赖性，并因此在培养中获得和维持马拉色菌酵母菌。无法使用传统实验室技术，尽管描述了许多种属，但无法准确鉴定。1989 年，马拉色菌属 (Baillon 1889)，也是由 Sabouraud 后于 1904 年提出的通用名糠秕孢子菌，仅包括两个分类群：一种在人类皮肤上发现的脂质依赖性的糠秕孢子菌(卵形糠秕孢子菌、圆形糠秕孢子菌)，和从动物上尤其是犬的皮肤中分离出来的一种厚皮马拉色菌(厚皮糠秕孢子菌、犬糠秕孢子菌)。
In 1990, Simmons and Gueho described the new species M. sympodialis which was characterized by a sympodial budding process. In 1996, Gueho et al. had the opportunity to collect and examine many isolates from humans and animals. Conventional and modern spectrum techniques were employed to characterise these isolates, encompassing morphology, ultrastructure, physiology and molecular biology. The result was a complete revision of the genus Malassezia and the description of four new species (M. obtusa, M. globosa, M. slooffiae and M. restricta).Eleven more species were described subsequently by different groups and from varied hosts: M. dermatis, M. japonica and M. yamatoensis from humans in Japan; M. nana from cases of otitis externa in cats and cattle; M. caprae from goats; M. equina from horses; M. cuniculi from rabbits; M. arunalokei from humans in India; M. brasiliensis and M. psittaci from domesticated parrots in Brazil; and M. vespertilionis from bats in the USA. Of these, to date, M. pachydermatis, M. furfur, M. sympodialis, M. globosa, M. slooffiae, M. nana, M. caprae, M. equina, M. cuniculi, M. brasiliensis, M. psittaci and M. verspertilionis have been isolated from animals and are therefore relevant in veterinary dermatology (Table 1). 1990 年，Simmons 和 Gueho 描述了以合孢子出芽过程为特征的新种合轴马拉色菌。1996 年 Gueho等人有机会收集和检查许多人和动物的分离株。采用传统和现代光谱技术对这些分离株进行表征，包括形态学、超微结构、生理学和分子生物学。结果是对马拉色菌属进行了完整的修订，并对 4 个新种（钝形马拉色菌、球形马拉色菌、斯洛菲马拉色菌和限制马拉色菌）进行了描述。随后不同组和不同宿主描述了另外 11 个种属：来自日本人的真皮马拉色菌、粳稻马拉色菌和大和马拉色菌；来自猫和牛外耳炎病例的娜娜马拉色菌；来自山羊的山羊马拉色菌；来自马的马属马拉色菌；来自兔的兔马拉色菌；来自印度人的印度马拉色菌；来自巴西家养鹦鹉的巴西马拉色菌和鹦鹉热马拉色菌；来自美国蝙蝠的蝙蝠马拉色菌。其中，厚皮马拉色菌、糠秕马拉色菌、合轴马拉色菌、球形马拉色菌、斯洛菲马拉色菌、娜娜马拉色菌、山羊马拉色菌、马属马拉色菌、兔马拉色菌、巴西马拉色菌、鹦鹉热马拉色菌和蝙蝠马拉色菌已从动物中分离出来，因此与兽医皮肤病学相关（表 1）。
Table 1. Summary of the taxonomy and ecology of the genus Malassezia 表 1.马拉色菌属的分类学和生态学概述 | Description and authors [reference] 描述和作者[参考] | | | | | | Pityrosporum ovale 卵形糠秕孢子菌 | HS (dogs, cats, others) HS（犬、猫、其他） | HS, PV, fungaemia HS，PV，真菌血症 | | | P. pachydermatis, P. canis 厚皮马拉色菌, P. 犬 | HS + LS (dogs, cats, many others, mostly canids) HS + LS（犬、猫、许多 其他，主要是犬科动物） | HS (dog contact), fungaemia HS（犬接触）， 真菌血症 | | | M. furfur serovar A 糠秕马拉色菌血清型 A | | | | 1996, Midgley, Gueho & Guillot
| P. orbiculare, M. furfur serovar B 圆形假单胞菌，M。 皮毛血清型 B | | | | 1996, Midgley, Guillot & Gueho
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| | | | 1996,Guillot,Midgley&Gue ho |
| HS (pigs, cat claws) HS（猪、猫爪） | | | 1996,Gue ho,Guillot&Midgley | M. furfur serovar C 糠秕马拉色菌血清型 C | | | | |
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| HS (cats, horses), OT (cats, cattle) HS（猫、马）、OT（猫、 牛） | | | |
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| | | | 2016, Honnavar, Rudramurthy, & Prasad
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— not reported, AD atopic dermatitis, HS healthy skin, LS lesional skin, PV pityriasis versicolor, SD seborrhoeic dermatitis, OT otitis. — 未报告， AD 特应性皮炎，HS 健康皮肤，LS 皮肤病变，PV 花斑癣，SD 脂溢性皮炎，OT 耳炎。
Malassezia species are lipid dependent due to an inability to synthesize long-chained (C14 or C16) fatty acids de novo. There are some differences in lipid dependence among the species and this variability has been used for the development of specific tests for the identification. Historically M. pachydermatis was regarded as being “lipophilic but not lipid-dependent” because it was the only member of the genus to grow on Sabouraud’s dextrose agar. Recently, genome sequencing has confirmed that M. pachydermatis lacks a fatty acid synthase gene like the other members of the genus, but is uniquely able to utilise lipid fractions within the peptone component of Sabouraud’s dextrose agar for growth. These observations explain its failure to grow on lipid-free defined media and thus M. pachydermatis should now also be regarded as being “lipid-dependent”. 由于无法从头合成长链（C14 或 C16）脂肪酸，马拉色菌属具有脂质依赖性。种属间的脂质依赖性存在一些差异，该变异性已用于开发鉴别的特定检测。历史上厚皮马拉色菌被认为是“亲脂性但非脂质依赖性”，因为它是该菌属中唯一在沙氏葡萄糖琼脂上生长的成员。最近，基因组测序证实厚皮马拉色菌与该属的其他成员一样缺乏脂肪酸合成酶基因，但独特地能够利用沙氏葡萄糖琼脂的蛋白胨组分内的脂质部分进行生长。这些观察结果解释了其在无脂限定培养基上不能生长，因此厚皮马拉色菌现在也应被视为“脂依赖性”。
The phenotypic identification scheme for the routine identification of Malassezia currently includes microscopic features, ability to use lipid supplements (different Tweens and cremophor EL [polyethoxylated castor oil]), catalase and beta-glucosidase reactions, and temperature tolerance at 32°C, 37°C and 40°C (Table S1). Despite the undisputable value of this phenotypic identification scheme, ambiguous results are sometimes reported. Furthermore, the addition of recently identified species resulted in similar physiological patterns and thus in a doubtful identification (M. arunalokei and M. brasiliensis are closely related to M. restricta and M. furfur, respectively) (Table S1). For all these reasons, specific identification should be confirmed by DNA sequencing analysis. Various molecular loci had been proposed to identify Malassezia species (Section 9). The most frequently used loci are the D1/D2 domain of the 26S rRNA gene and the internal transcribed spacer (ITS) regions.Other genes such as chitin synthase-2 and ß-tubulin have been proposed for taxonomic purposes. Recently, mass spectrometry has also been utilised for the identification of Malassezia yeasts isolated from human patients in three French university hospitals.A MALDI-TOF database of main mass spectra has recently been developed to allow the rapid identification of 14 Malassezia species. 马拉色菌常规鉴定的表型鉴定方案目前包括显微特征、使用脂质补充剂的能力（不同的 Tweens 和 cremophor EL [聚乙氧基化蓖麻油]）、过氧化氢酶和 β-葡萄糖苷酶反应以及 32 ℃、37 ℃ 和 40 ℃ 的温度耐受性（表 S1）。尽管这种表型鉴定方案的价值是无可争议的，但有时报告的结果模棱两可。此外，增加最近鉴定的菌种得到了相似的生理模式，因此鉴定结果可疑（分别为印度马拉色菌和巴西马拉色菌与限制马拉色菌和糠秕马拉色菌密切相关）（表 S1）。由于所有这些原因，特异性鉴定应通过 DNA 测序分析进行确认。已提出各种分子位点来鉴定马拉色菌属（第 9 节）。最常用的位点是 26S rRNA 基因的 D1/D2 结构域和内转录间隔区 (ITS) 区域。其他基因如甲壳素合成酶-2 和 ß-微管蛋白已被提出用于分类学目的。最近，质谱也被用于鉴定从法国三家大学医院人类患者中分离的马拉色菌酵母菌。最近开发了主要质谱的 MALDI-TOF 数据库，可快速鉴定 14 种马拉色菌。
2.1 Conclusions 2.1 结论 Malassezia yeasts are unique in several ways, including their strict dependence on lipids, their cellular ultrastructure and their dominance as eukaryotic residents on the skin of warm-blooded vertebrates. The taxonomy of the genus Malassezia is evolving. Eighteen species have been described so far but many other species are most probably present on the skin or mucosal sites of warmblooded animals. Few phenotypic tests are available to differentiate Malassezia species and some of them may overlap. As a consequence, DNA sequencing (or other techniques like mass spectrometry) may be required for specific identification. 马拉色菌酵母菌在几个方面是独特的，包括它们对脂质的严格依赖、它们的细胞超微结构和它们在温血脊椎动物皮肤上作为真核生物的优势。马拉色菌属的分类学正在演变。到目前为止，已描述了18个种属，但许多其他种属最有可能存在于温血动物的皮肤或粘膜部位。目前用于区分马拉色菌的表型检测方法很少，其中一些可能重叠。因此，可能需要DNA测序（或其他技术，如质谱）进行特异性鉴定。
3 Historical aspects of Malassezia yeasts as skin pathogens in dogs and cats 3 马拉色菌酵母菌作为犬猫皮肤病原体的历史方面 3.1 Introduction: prehistory facilitating discovery 3.1 引言：史前促进发现 Analysis of the history of scientific discovery highlights the influence of language and geography, the role of experts and opinion leaders in study centres or in the modern day “centres of excellence”, and wider cultural effects that may impede or enhance investigation and implementation of technological advances in the pursuit of scientific progress. The fascinating history of the genus Malassezia and its role in disease spans four centuries and three continents and extends from early microscopical observations through to present day genome sequencing. After a [final] flurry of controversy in the late 20th century, this body of evidence culminated in development of the disease model that veterinarians use today. 对科学发现历史的分析强调了语言和地理的影响，研究中心或现代“卓越中心”中专家和意见领袖的作用，以及可能阻碍或加强在追求科学进步的过程中调查和实施技术进步的更广泛的文化影响。马拉色菌属的迷人历史及其在疾病中的作用跨越了4个世纪和3个大陆，从早期的显微镜观察延伸到现在的基因组测序。在20世纪末的一连串争议之后，这一系列证据最终导致了兽医今天使用的疾病模型的发展。
3.2 The first reports of the yeast and disease 3.2 酵母菌的首次报道和疾病 3.2.1 Early reports 3.2.1 早期报道 1846: Karl Ferdinand Eichstedt was the first to observe hyphal elements and blastoconidia in scale from his patients and attributed these to cause a human skin disease he called “Pityriasis versicolor”. 1846 年：Karl Ferdinand Eichstedt 是首次从他的患者身上的皮屑中观察到菌丝元素和芽生孢子的人，并将其归因于引起一种他称之为“花斑糠疹”的人类皮肤病。
1853: Charles Robin named Eichstedt’s fungus as Microsporon furfur, believing it to be a dermatophyte, and termed the associated skin disease “Tinea versicolor”. 1853 年：Charles Robin 将 Eichstedt 的真菌命名为糠秕小孢子菌，认为它是一种皮肤癣菌，并将相关的皮肤病称为“花斑癣”。
1873: Sebastiano Rivolta, an Italian veterinarian, noticed a double-contour budding yeast in human “psoriatic” scales and gave them the name Cryptococcus psoriasis. 1873 年：意大利兽医 Sebastiano Rivolta 注意到人类“银屑病”皮屑中有一种双轮廓芽殖酵母菌，并将其命名隐球菌银屑病。
1874: Frenchman Louis Charles Malassez suggested that Microsporon furfur caused dandruff and correctly differentiated the yeast into genus of single cell fungi (“Saccharomyces”) rather than the dermatophyte complex. For this correction, his name was ultimately attached to the genus. 1874：法国人Louis Charles Malassez 认为糠秕小孢子菌引起头皮屑，并将酵母正确分化为单细胞真菌属（“酵母菌”），而不是皮肤癣菌复合体。为了这次更正，他的名字最终被附在该属上。
3.2.2 Attempts at classification without laboratory isolation 3.2.2 在没有实验室分离的情况下尝试分类 1884: Bizzozero studied these microbes and described them to be part of normal human skin flora. He claimed there were two different species and named them Saccharomyces ovalis and S. sphaericus. However, these were later shown to be a single species. 1884 年：Bizzozero 研究了这些微生物，并将它们描述为正常人皮肤菌群的一部分。他声称有两种不同的菌种，并将它们命名为卵形酵母菌和球形酵母菌。 然而，这些后来被证明是单一物种。
1889: Baillon created the genus Malassezia to accommodate M. furfur, in honour of Malassez, who was already acknowledged as having described the new species – at least in the French-speaking scientific community. However this particular yeast could not be grown and isolated in laboratory conditions because its lipid requirement in culture media were as yet unknown. 1889 年：Baillon 创建了马拉色菌属来容纳糠秕马拉色菌，以纪念承认Malassez描述了新物种——至少在法语科学界是如此。然而，这种特殊的酵母菌不能在实验室条件下生长和分离，因为它在培养基中的脂质需求尚不清楚。
1910: Raymond Sabouraud, a prominent medical mycologist, proposed the name Pityrosporum malassezi for this bottle shaped yeast thought to cause human dandruff.
1910 年：著名的医学真菌学家 Raymond Sabouraud 为这种被认为会引起人类头皮屑的瓶形酵母菌提出了马拉色糠秕孢子菌的名称。
1913: Alfred Kraus was able to culture P. malassezi in a medium containing lanolin.In a prime example of the effect of geography and historical events on scientific discovery, this German scientist’s work was largely overlooked with the onset of the First World War.
1913 年：Alfred Kraus 能够在含有羊毛脂的培养基中培养马拉色糠秕孢子菌。在地理和历史事件对科学发现影响的一个主要例子中，随着第一次世界大战的开始，这位德国科学家的工作在很大程度上被忽视了。
3.2.3 Diseases associated with Malassezia 3.2.3 马拉色菌相关疾病 1925: Weidman reported bottle shaped yeast from the scale of the single horned Indian rhinoceros (Rhinoceros unicornis) with a generalised exfoliative dermatitis. In contrast to M. furfur this yeast cultivated readily on routine media without lipid supplementation. Weidman classified the yeast in the genus Pityrosporum, with the species name P. pachydermatis. The rhinoceros responded rapidly to topical therapy with 1% salicylic acid in lard. 1925 年：Weidman 报道了来自患有全身性表皮剥脱性皮炎的单角印度犀牛 (大独角犀) 皮屑的瓶形酵母菌。与糠秕马拉色菌相比，这种酵母菌在不添加脂质的常规培养基上很容易培养。Weidman 将该酵母菌归类于糠秕孢子菌属，菌种名称为厚皮马拉色菌 。犀牛对1%水杨酸猪油溶液外部治疗反应迅速。
1928–1929: McLeod and Dowling part-fulfilled Koch’s postulates by isolation of M. furfur from humans with seborrhoeic dermatitis in an oleic acid broth.They then inoculated lesion-free skin of a person with seborrhoeic dermatitis and a normal human with the broth isolate and reproduced seborrhoeic lesions in both, from which they re-isolated M. furfur. An incidental finding was an association between the dandruff, yeast and a concurrent coccoid bacterium that was carefully separated and subcultured. MacLeod and Dowling regarded these pyogenic micrococci as secondary invaders, even accepting it was constantly associated with seborrhoeic dermatitis. Interestingly, MacLeod and Dowling referred to three names of the yeast in their work: the “spore of Malassez”, “Pityrosporum of Sabouraud” or the “flask bacillus of Unna”. Until now, no consensus had been reached as to whether these names covered a single organism, whether it was pathogenic and what disease was caused. This work was later confirmed by Moore et al. 1928-1929：McLeod 和 Dowling 通过在油酸肉汤培养基中分离患有脂溢性皮炎的人的糠秕马拉色菌，部分实现了 Koch 的假设。然后，他们用肉汤分离株接种脂溢性皮炎患者和正常人的无皮损皮肤，并在两者中复制脂溢皮损，从中重新分离出糠秕马拉色菌。一个偶然的发现是头皮屑、酵母菌和并发的球形细菌（经过仔细分离和传代培养）之间的关联。MacLeod 和 Dowling 将这些化脓性微球菌视为继发性入侵者，甚至接受它与脂溢性皮炎总是相关。有趣的是，MacLeod和Dowling在他们的工作中提到了酵母菌的三个名称：“Malassez 的孢子”、“Sabouraud 的糠秕孢子菌”或“Unna 的杆菌”。直到现在，关于这些名称是否涵盖单一的生物体、是否致病以及引起了什么疾病，还没有达成共识。Moore 等人随后证实了这项工作。
These publications, discussions and controversies were a prerequisite to unravelling the role of Malassezia spp. in skin diseases of the dog and cat. 这些出版物、讨论和争议是解开犬猫皮肤病中马拉色菌作用的先决条件。
3.2.4 The controversy and ‘Dark Years’: 1940 to 1960 3.2.4 争议与 ‘ 黑暗年 ’：1940～1960 年 1940–1960: are known as the ‘Dark Years’ and spanned a period of more controversy. The hard won progress in the field was forgotten as a consequence of the Second World War and the overwhelming effect of cortisone treatment becoming available in the late 1940s, to which human seborrhoeic dermatitis responded. The role of Malassezia yeasts in the disease was thus forgotten. 1940-1960 年：被称为 ‘ 黑暗年 ’，跨越了一个争议更多的时期。由于第二次世界大战和可的松治疗的压倒性效果在20世纪40年代末开始应用，人类脂溢性皮炎对其产生了反应，该领域的来之不易的进展被遗忘。马拉色菌酵母菌在该病中的作用由此被遗忘。
1970: The systematics were rectified when Sloff in Lodder’s ‘The Yeasts, a taxonomic study’ assigned all Pityrosporum that grew on media without lipid enrichment as single species of P. pachydermatis. 1970 年：Sloff在Lodder 的《酵母菌，分类学研究》中对其分类进行了修正，将所有在无脂质富集的培养基上生长的糠秕孢子菌指定为厚皮马拉色菌的单一菌种。
1984: The third edition of “The Yeasts, a Taxonomic Study” (Yarrow and Ahearn) referred to the new genus Malassezia and confirmed that one species grew without lipid enrichment. This was later officially added into the taxonomical order. 1984 年：第三版《酵母菌，分类学研究》(Yarrow and Ahearn) 提到了马拉色菌新属，并证实有一个菌种在没有脂质富集的情况下生长。这后来被正式添加到分类学顺序中。
1990: A new species, Malassezia sympodialis was described and by 1996 four new species were added to the genus. This species was later isolated from a cat by Bond et al. in 1996. 1990 年：描述了一个新种，即合轴马拉色菌，到1996年，该属增加了四个新种。Bond 等后来在1996年从猫中分离出该物种。
3.2.5 Modern approaches 3.2.5 现代方法 Currently there are 18 different species of Malassezia. The genus continues to expand and this is likely to continue as the classical ‘bottom-up’ microbiological approaches merge with organism-level genomics and community or “systems-level meta-genomics”. 目前马拉色菌有 18 种不同种属。其还会继续扩展且随着经典的“自下而上”的微生物学方法与生物体水平的基因组学和群落或“系统水平的元基因组学”融合而很可能会继续。
3.3 Malassezia yeasts in animals 3.3 动物中的马拉色菌酵母菌 3.3.1 Canine ear and skin disease: the first reports (1951 to 1999) 3.3.1 犬耳道和皮肤上的疾病：首次报道（1951～1999 年）
The discovery of Malassezia in animals occurred at a much later date than in humans. As mentioned, Weidman isolated yeasts from the skin of a rhinoceros in 1925, but research in domestic animals largely re-started 30 years later. 动物中马拉色菌的发现比人类晚得多。如上所述，weidman 于 1925 年从犀牛的皮肤中分离出酵母菌，但在家畜中的研究基本上在30年后重新开始。
3.3.2 Malassezia yeasts in the canine and feline ear 3.3.2 犬猫耳道的马拉色菌酵母菌
1955: Gustafson was the first to notice a bottle shaped yeast in otitis externa of a dog; he correctly recognized them as Pityrosporum and created a new species P. canis. This was in error as he had misread Lodder’s description and failed to consider Weidman’s discovery of the yeast in rhinoceros skin, which grew without lipid enrichment. Gustafson was able to induce a spontaneously-resolving erythemato-ceruminous otitis externa in healthy dogs by the application of a suspension of ‘P. canis’ to the external ear canal. 1955年：Gustafson 首次在犬的外耳炎中注意到瓶形酵母菌；他正确地认识到它们是糠秕孢子菌，并创造了一个新种类犬糠秕孢子菌。这是错误的，因为他误解了Lodder 的描述，没有考虑 Weidman 在犀牛皮肤中发现这种酵母菌，这种酵母在没有富含脂质的情况下生长。Gustafson 通过在健康犬外耳道涂抹“犬糠秕孢子菌”混悬液，能够诱导自行消退的红斑性耵聍性外耳炎。
1961: Fraser also isolated and studied strains of yeast from healthy and diseased dog ears and correctly ascribed all as P. pachydermatis. During the next two decades, a number of studies showed the connection between canine otitis externa and P. pachydermatis.
1961年：Fraser 还从健康犬和患病犬耳道中分离和研究了酵母菌菌株，并正确地将其归因于厚皮马拉色菌。在接下来的二十年中，多项研究显示了犬外耳炎与厚皮马拉色菌之间的联系。
1976: Baxter also showed that, unlike previously thought, the frequency of isolation of P. pachydermatis was comparable in healthy ears and in cases of otitis externa in dogs’ and cats’ ears.
1976 年：Baxter 还表明，与以前认为的不同，厚皮马拉色菌在健康耳和犬猫外耳炎病例患耳中的分离频率相似。
3.3.3 Canine skin disease 3.3.3 犬皮肤病
1975: Dufait was the first to describe the skin disease, albeit in a local veterinary journal written in Dutch. Also later, several non-English language studies were published, all describing canine Malassezia dermatitis; however, without a widespread English audience, many pruritic dogs suffered as a result of this disadvantage. 1975 年：Dufait 首次描述了这种皮肤病，尽管是在荷兰当地的兽医杂志上。随后，发表了几项非英语语言的研究，均描述了犬马拉色菌皮炎；然而，由于没有广泛的英国观众，许多瘙痒犬只遭受了这种不利的结果。
1987: Mason spoke about three canine Malassezia dermatitis cases at the American Academy/College of Veterinary Dermatology meeting, creating objection and controversy, although another speaker from private speciality practice advised that he has seen a similar case. Similar discussions ensued at a lecture in 1992 at the British Veterinary Dermatology Study Group spring meeting. One highlight of the debate was mention of Shuster’s publication that showed that dandruff was clearly associated with “Pityrosporum ovale”, elegantly dismissing the distorted view that effective dandruff treatments were cytostatic rather than antimycotic in action. 1987 年：Mason在美国兽医皮肤病学会/学院会议上谈到了三例犬马拉色菌皮炎病例，产生了异议和争议，尽管来自私人专科诊所的另一位演讲者建议他已经看到了类似的病例。1992 年在英国兽医皮肤病研究组春季会议上的一次讲座中也进行了类似的讨论。争论的一个亮点是提到 Shuster 的出版物，显示头皮屑明显与“卵形糠秕孢子菌”相关，优雅地驳斥了有效的头皮屑治疗在作用上是细胞抑制而不是抗真菌的扭曲观点。
1988: Larsson et al. drew attention to Malassezia skin disease in the English language by describing the skin disease associated with P. pachydermatis. Mason and Evans confirmed and expanded on those earlier observations, although acceptance by the veterinary profession was not universal. 1988:Larsson 等人通过描述与厚皮马拉色菌相关的皮肤病，虽然用英语引起人们对马拉色菌皮肤病的关注。Mason和 Evans证实并扩展了早期的观察结果，但兽医行业的接受度并不普遍。
1992: Pedersen published in Danish a case series of 10 dogs with Malassezia dermatitis.He described the cytology, mycology, histopathology and the results of antifungal treatment. The before and after clinical photographs left no doubt about the dramatic health and welfare benefits of the antifungal therapy in these cases. 1992：Pedersen在丹麦发表了10只马拉色菌皮炎犬的病例分析。他描述了细胞学、真菌学、组织病理学和抗真菌治疗的结果。在这些病例中，临床前后的照片无疑表明了抗真菌治疗对健康和福利益处。
1996: Mason et al. followed up on knowledge of Malassezia associated dermatitis, staphylococcal pyoderma and demodicosis and integrated these into a unifying concept of skin commensals as opportunistic and complementary pathogens. By this time, the initial controversy that had dogged the profession regarding the significance of Malassezia yeasts as a cause for dermatitis in the canine had largely settled. 1996：Mason 等人随访马拉色菌相关皮炎、葡萄球菌性脓皮病和蠕形螨病的知识，并将其整合到皮肤共生菌作为条件和补充病原体的统一概念中。此时，关于马拉色菌酵母菌作为犬皮肤病病因的意义，困扰该行业的最初争议已基本解决。
Present day: Currently, Malassezia pachydermatis is now well-recognized as a commensal yeast of dog’s skin and mucosa; overgrowth is commonly associated with otitis externa and dermatitis. Research continues in further characterising the relative pathogenicity of the differentspecies and genotypes, and elucidating the factors that drive the conversion to pathogen (Figure 1a–c). 当今：目前，厚皮马拉色菌是公认的犬皮肤和粘膜共生酵母菌；过度增殖通常与外耳炎和皮肤病有关。研究继续进一步表征不同物种和基因型的相对致病性，并阐明驱动转化为病原体的因素（图 1a–c）。
Figure 1. The numbers of publications on Malassezia pachydermatis by year (a) and for dogs (b) and cats (c) from 1900 to present day. 图 1. 1900 年至今按年份 (a) 以及按犬 (b) 和猫 (c) 分列的厚皮马拉色菌出版物数量。
3.3.4 Malassezia yeasts in cats: rare or common? 3.3.4 猫的马拉色菌酵母菌：罕见还是常见？ The role of Malassezia spp. in feline skin disease beyond the ear canal had not aroused much interest until the research into canine and human Malassezia spp. carriage and associated dermatitis prompted some further work in the mid to late 1990’s. 马拉色菌的作用。在猫耳道以外的皮肤病中，直到对犬和人马拉色菌的研究才引起人们的广泛兴趣。20世纪90年代中后期，携带和相关皮肤病促使了一些进一步的工作。
1976: Baxter was the first to report on M. pachydermatis in cat ears and as previously mentioned, found that Malassezia were also present in the ears of healthy animals. In 1990 Hajsig and Hajsig confirmed that M. pachydermatis is a normal part of cat skin microflora. 1976 年：Baxter 首次报道了猫耳道厚皮马拉色菌，如前所述，发现健康动物耳部也存在马拉色菌。1990年Hajsig和Hajsig证实厚皮马拉色菌是猫皮肤菌群的正常部分。
At the time Malassezia dermatitis was considered extremely rare or unknown in the cat. A causal relationship between the overgrowth of Malassezia in the cat and the development of seborrhoeic dermatitis was proposed in 1994. The two cats discussed had generalized exfoliative and greasy erythroderma which responded to antifungal therapy. 当时认为马拉色菌皮炎在猫中极为罕见或未知。1994年提出猫体内马拉色菌过度增殖与出现脂溢性皮炎有因果关系。讨论的两只猫患有全身性表皮剥脱性油腻性红皮病，抗真菌治疗有效。
1996: The isolation of M. globosa from skin of a healthy cheetah (Acinonix jubatus) represented the first report of lipid-dependent Malassezia spp from Felidae.Bond et al. isolated the first lipid dependent species (Malassezia sympodialis) from domestic cat skin. Subsequent studies by the same group and other groups in Spain and Japan led to reports on the isolation of M. globosa, M. furfur, M. nana and, more recently, M. slooffiae from domestic cats. 1996 年：从健康猎豹 (Acinonix猎豹) 皮肤中分离出球形马拉色菌代表了猫科动物脂质依赖性马拉色菌属的首次报告。Bond 等人从家猫皮肤中分离出第一个脂质依赖菌种（合轴马拉色菌）。随后由西班牙和日本的同一研究小组和其他研究小组进行的研究报道了从家猫中分离出的球形马拉色菌、糠秕马拉色菌、娜娜马拉色菌和最近的斯洛菲马拉色菌。
2002: Mauldin et al. evaluated the presence of Malassezia yeasts in feline skin specimens submitted for histopathological examination from 1999 to 2000. Of the 15 cats with Malassezia, 11 presented with an acute onset of multifocal to generalized skin lesions and were euthanised or died within two months. In contrast to humans and dog, Malassezia overgrowth in the cat, in the absence of hypersensitivity disorder or a breed predilection (Devon rex, sphynx) may indicate a poorer prognosis due to an association with life-threatening systemic diseases. 2002:Mauldin等人评价了 1999 年至 2000 年提交进行组织病理学检查的猫皮肤标本中是否存在马拉色菌酵母菌。在15只马拉色菌猫中，11 只表现为急性发作的多灶性至全身性皮肤病变，并在两个月内安乐死或死亡。与人类和犬相比，马拉色菌在猫中过度增殖、无超敏反应疾病或品种好发 (德文卷毛猫、斯芬克斯猫) 可能表明预后较差，因为与危及生命的全身性疾病有关。
2005: Cafarchia et al.reported that both the frequency of isolation and population sizes of M. pachydermatis was increased in cats with otitis externa, when compared with healthy cats. 2005年:Cafarchia 等人报告称，与健康猫相比，患有外耳炎的猫中厚皮马拉色菌的分离频率和种群数量均增加。
2007: Cats with seborrhoeic and allergic presentations were shown to have concurrent M. pachydermatis overgrowth that responded clinically to azole antifungal therapy, in parallel to the situation in dogs.
2007 年：具有脂溢性和过敏性表现的猫显示并发厚皮马拉色菌过度增殖，临床上对唑类抗真菌治疗有反应，与犬中的情况类似。
3.4 Conclusions 3.4 结论 The history of the association between Malassezia yeasts and its animal hosts has been long mired in controversy. Recent genomic studies have elucidated previously problematical aspects of taxonomy and indicated that genotypes and species of Malassezia are evolving as an adaptation to particular host ecological niches. Having been previously overlooked, canine Malassezia dermatitis has evolved from a controversial to a routine now diagnosis in small animal practice, with very significant welfare benefits for many animals. 马拉色菌酵母菌与其动物宿主之间关联的历史长期深陷争议之中。最近的基因组研究阐明了分类学中以前存在问题的方面，并表明马拉色菌的基因型和种类正在进化，作为对特定宿主生态位的适应。犬马拉色菌皮炎以前被忽视过，在小动物实践中已从有争议的发展到现在的常规诊断，对许多动物具有非常显著的福利益处。
4 Ecology and epidemiology 4 生态学和流行病学
4.1 Introduction 4.1 引言
Malassezia yeasts are common skin commensals in warm-blooded vertebrates. The loss of fatty acid synthetase genes (Section 2), resulting in a requirement for a lipid source for growth, is likely one factor linking them to animal hosts. In one review, it was proposed that Malassezia yeasts are potential pathogens that operate in a pliable, physiological “transitional mantel zone” that is influenced by both host skin and the animal’s external environment. Thus, yeast proliferation may be enhanced by either favourable environmental conditions (heat, humidity) and or changes in host susceptibility (Section 7). 马拉色菌酵母菌是温血脊椎动物常见的皮肤共生菌。脂肪酸合成酶基因的丢失（第 2 节）导致生长需要脂质来源，可能是将其与动物宿主联系起来的一个因素。在一篇综述中，提出马拉色菌酵母菌是潜在的病原体，在柔韧、生理的“过渡区域”中运作，受宿主皮肤和动物外部环境的共同影响。因此，有利的环境条件（热、湿度）和/或宿主易感性变化均可增强酵母菌增殖（第 7 节）。
Many culture-based studies have been carried out worldwide both in humans and in animals (especially in dogs) to better understand the ecology of Malassezia species on healthy skin and in cases with cutaneous lesions. Results are rarely comparable between studies because of the use of different sampling procedures, culture media and identification techniques. The influence of sampling methods and culture media on yeast counts are reviewed in Section 8. The general conclusion is that M. pachydermatis remains by far the most important and prevalent species in dogs while the other lipid-dependent species are detected quite frequently in certain animal species (like cats) or body sites. Some of these lipid-dependent species seem to be host-specific (Table 1). In humans, three species (M. globosa, M. restricta and M. sympodialis) predominate. Interestingly human-related species may have a different geographical distribution; M. dermatis has been isolated in East Asia, M. arunalokei in India, whereas M. obtusa was mostly reported from Sweden, Canada, Bosnia and Herzegovina. 在全球范围内，在人类和动物（尤其是犬）中进行了许多基于培养的研究，以更好地了解马拉色菌属在健康皮肤上和皮肤病变病例中的生态学。由于使用了不同的采样程序、培养基和鉴定技术，研究之间的结果很少具有可比性。在第8节中综述了采样方法和培养基对酵母菌计数的影响。一般结论是厚皮马拉色菌仍然是犬中最重要和最普遍的种属，而其他脂质依赖性种属在某些动物种属（如猫）或身体部位中相当常见。其中一些脂质依赖性种属似乎具有宿主特异性（表1）。在人类中，以 3 种（球形马拉色菌、限制马拉色菌和合轴马拉色菌）为主。有趣的是，与人类相关的种属可能具有不同的地理分布；在东亚分离出了真皮马拉色菌，在印度分离出了印度马拉色菌，而在瑞典、加拿大、波斯尼亚和黑塞哥维那主要报告了钝形马拉色菌。
Malassezia yeasts have been isolated from almost all domestic animals, different wild animals in captivity and also from wildlife. An exhaustive list of potential animal hosts was reported in 2010. In addition, the presence of Malassezia-like organisms has been reported in a wide range of environmental habitats, from deep sea sediments, hydrothermal vents and arctic soils, to marine sponges, stony corals, eels, lobster larvae and nematodes. 马拉色菌酵母菌已从几乎所有家畜、圈养的不同野生动物以及野生动物中分离得到。2010年报告了潜在动物宿主的详尽列表。此外，据报道，马拉色菌样生物的存在在广泛的环境生境中，从深海沉积物、热液喷口和北极土壤，到海洋海绵、石珊瑚、鳗鱼、龙虾幼虫和线虫。
In recent years methods based on next generation sequencing (NGS) have allowed a better characterization of the complex microbial communities occurring on the skin and made it possible to detect Malassezia species that would otherwise be missed using culture-based methods (Section 4.4). 近年来，基于下一代测序 (NGS) 的方法能够更好地表征发生在皮肤上的复杂微生物群落，并使使用基于培养的方法检测可能遗漏的马拉色菌属的检测成为可能（第4.4节）。
4.2 Ecology of Malassezia yeasts in dogs 4.2 犬马拉色菌酵母菌的生态学 Colonisation of canine skin probably occurs in the very first days of life; how this occurs is not understood but likely involves transfer from the bitch’s flora following removal of the amniotic membrane, licking and nursing in the same manner as staphylococci. In a study performed in 22 newborn Rottweiler puppies, Malassezia yeasts were recovered from around 40% of samples collected from the lips,nail beds and ears, at three, seven and 35 days of age. 犬皮肤定植可能发生在出生后最初几天；其发生方式尚不清楚，但可能涉及在后从母犬菌群转移，去除羊膜，舔和哺乳的方式，与葡萄球菌相同。在对22只新生罗威纳幼犬进行的一项研究中，在3日龄、7日龄和35日龄时，从嘴唇、甲床和耳部采集的约40%样本中回收到马拉色菌酵母菌。
Several investigators have explored Malassezia colonization in various anatomical regions of different breeds of adult healthy dogs; example studies that utilised culture methods are summarised in Table S2. There is some variability in the data, reflecting in part varied sampling methods; however, it can be seen that the sites most frequently colonised by M. pachydermatis in healthy pet dogs of various breeds are the peri-oral/ lip region (81% of 58 dogs sampled using contact plates) and interdigital skin ((60–70% of 40 dogs sampled using contact plates) whereas the yeast is less-often detected in the skin of the axilla (12.5% of 40), groin (23% of 91) and dorsum (4% of 73). The perianal skin and anal mucosa is a frequent (~55% of 73 dogs) carriage site whereas nasal and oral carriage is less frequent. Using cytological techniques, it was reported that the highest number of Malassezia were on the chin region, while inguinal and axillary zones presented the lowest number. Malassezia yeasts were identified by cytological methods in 10–31% of examined anal sacs in two studies of groups of healthy dogs (n = 57), usually in low numbers. Malassezia yeasts were detected on the periocular skin of only three out of 56 (5%) clinically normal dogs. Basset hounds show a marked breed variation, with significantly increased frequencies and population sizes of M. pachydermatis in the nose, mouth, vulva and axilla. 一些研究者探索了马拉色菌在不同品种成年健康犬不同解剖区域的定植；使用培养方法的示例研究总结见表S2。数据存在一定的变异性，部分反映了不同的采样方法；但是，可以看出，在不同品种的健康宠物犬中，厚皮马拉色菌最常定植的部位是口周/唇区（使用接触板采样的 58 只犬中的81%）和趾间皮肤（使用接触板采样的 40 只犬中的 60-70%），而在腋窝皮肤中较少检测到酵母菌 （40例的 12.5%）、腹股沟（91例的23%）和背部（73例的4%）。肛周皮肤和肛门粘膜是常见的（约占73 只犬的 55%）携带部位，而鼻腔和口腔携带频率较低。据报道，使用细胞学技术，马拉色菌在颏区的数量最多，而腹股沟区和腋窝区的数量最少。在健康犬组 (n = 57) 的两项研究中，通过细胞学方法在10-31% 的检查肛囊中鉴定出马拉色菌酵母菌，通常数量较少。在56只临床正常犬中仅3只 (5%) 的眼周皮肤上检测到马拉色菌酵母菌。巴塞特猎犬表现出明显的品种变异，鼻、口、外阴和腋窝厚皮马拉色菌的频率和种群数量显著增加。
Studies of oral carriage of Malassezia may have relevance as a source of transfer to the skin.Twiceweekly application of a miconazole-chlorhexidine shampoo to seborrhoeic Basset hounds resulted in a significant reduction of M. pachydermatis populations in both the skin and mouth. Another study pointed out the possible transfer of Malassezia yeasts between the perioral area and pruritic skin lesions of the inguinal area as a consequence of frequent licking, and between undamaged interdigital regions as a result of persistent scratching. 马拉色菌经口携带的研究可能作为转移至皮肤的来源具有相关性。每周两次对脂溢性巴塞特猎犬使用咪康唑-氯己定香波可显著减少皮肤和口腔中的厚皮马拉色菌数量。另一项研究指出，马拉色菌酵母菌可能在频繁舔舐导致的口周区域和腹股沟区域瘙痒性皮肤病变之间，以及由于持续搔抓导致的未受损趾间区域之间转移。
Other than M. pachydermatis, lipid-dependent Malassezia yeasts are infrequently reported from dog skin. In initial reports, the identification of lipid-dependent yeasts was based only on morphological and physiological characteristics. In the absence of molecular techniques, there is scope to confuse lipid-dependent Malassezia spp. with atypical strains of M. pachydermatis that show inconsistent or stable lipid-dependence. However, the presence of M. furfur was confirmed by molecular biology in dogs with cutaneous lesions or otitis in Brazil. In a survey in Slovakia, mycological cultures performed from dogs with cutaneous lesions (n = 118) and dogs with otitis externa (n = 328) yielded M. pachydermatis as the most frequently isolated species (121 isolates); however, four lipid-dependent isolates were identified as M. furfur and one as M. nana. 除厚皮马拉色菌外，脂质依赖性马拉色菌酵母菌很少见于犬皮肤。在最初的报道中，脂质依赖性酵母菌的鉴定仅基于形态和生理特征。在缺乏分子技术的情况下，有可能混淆脂质依赖性马拉色菌属。具有厚皮马拉色菌的非典型菌株，表现出不一致或稳定的脂质依赖性。然而，在巴西患有皮肤病变或耳炎的犬中，通过分子生物学证实了糠秕马拉色菌的存在。在斯洛伐克的一项调查中，对皮肤病变犬 (n = 118) 和外耳炎犬 (n = 328) 进行真菌学培养，得到厚皮马拉色菌为最常分离的菌种（121个分离株）；然而，4个脂质依赖性分离株被鉴定为糠秕马拉色菌，1个为娜娜马拉色菌。
4.3 Ecology of Malassezia yeasts in cats 4.3 猫的马拉色菌酵母菌的生态学 The skin of Felidae is colonized by a diverse array of Malassezia spp yeasts. Whilst M. pachydermatis is most frequent, as in dogs, the lipid-dependent species isolated from domestic cats include M. sympodialis, M. globosa, M. furfur, M. nana, and M. slooffiae. The original reports of isolation of M. furfur are based on phenotypic rather than molecular methods. The isolation of M. globosa from the skin of a healthy cheetah (Acinonix jubatus) represented the first report of lipid-dependent Malassezia spp from cats. In 2004, a study described M. nana, a novel species from aural discharges of a cat and cattle. Some lipid-dependent strains similar to the M. sympodialis type strain and isolated from cats were studied using DNA sequence analysis and grouped together with M. nana. Malassezia nana seems to be the most common lipid-dependent species isolated from cats, particularly in the ear canal; similarities in the sequences of three loci of the rRNA gene, ß-tubulin gene and microsatellite profiles indicate that a particular M. nana genotype predominates in this host. Malassezia slooffiae is primarily but not exclusively associated with the feline claw fold. 猫科动物的皮肤上有各种各样的马拉色菌酵母菌。虽然厚皮马拉色菌最常见，如在犬中，从家猫中分离的脂质依赖性菌种包括合轴马拉色菌、球形马拉色菌、糠秕马拉色菌、娜娜马拉色菌和斯洛菲马拉色菌。 最初分离糠秕马拉色菌的报道是基于表型而不是分子方法。从健康猎豹 (acinonix猎豹) 皮肤中分离出球形马拉色菌代表了猫脂质依赖性马拉色菌属的首次报告。2004 年，一项研究描述了娜娜马拉色菌，一种来自猫和牛耳分泌物的新物种。利用 DNA 序列分析方法研究了从猫中分离的一些脂质依赖性菌株，与合轴马拉色菌菌株相似，并与娜娜马拉色菌一起分组。娜娜马拉色菌似乎是从猫中分离出的最常见的脂质依赖性菌种，特别是在耳道中；rRNA 基因、ß-微管蛋白基因和微卫星图谱的三个位点序列的相似性表明，特定的娜娜马拉色菌基因型在该宿主中占主导地位。斯洛菲马拉色菌主要但不完全与猫爪褶有关。
Malassezia pachydermatis is less frequently isolated from cats than from dogs.Marked variations in Malassezia populations have been reported in the external ear canal of healthy cats. One study identified Malassezia yeasts in 43 out of 52 healthy cats sampled in the winter months in north eastern USA. By contast, another study failed to identify yeasts in 20 health cats sampled in France; notably in the latter study, the presence of cerumen was an exclusion criterion whereas cerumen was noted in many of the US cats, especially amongst those with a purely indoor lifestyle. Malassezia yeasts were detected in 20% (six of 30) ear canals of 15 cats with disease and in 43% (13 of 30) ear canals of 15 allergic cats. Devonrex cats and sphynx cats, but not Cornishrex cats, are prone to high carriage rates of Malassezia yeasts and a generalised seborrhoeic dermatitis that responds to oral itraconazole. Predisposing factors such as hypersensitivities and internal diseases that disrupt cornification are reviewed in Section 7. 厚皮马拉色菌从猫中分离的频率低于从犬中分离的频率。据报道，健康猫的外耳道中马拉色菌种群有明显的变异。一项研究在美国东北部冬季采集的 52 只健康猫中的 43 只中鉴定出马拉色菌酵母菌。相比之下，另一项研究未能在法国采样的20只健康猫中鉴定出酵母菌；尤其是在后一项研究中，耵聍的存在是一项排除标准，而在许多美国猫中观察到耵聍，尤其是在那些纯粹有室内生活方式的猫中。15只患病猫的 20% (6/30) 耳道和15只过敏猫的43% (13/30) 耳道检出马拉色菌酵母菌。德文卷毛猫和斯芬克斯猫（而非柯尼斯卷毛猫）容易出现马拉色菌酵母菌的高携带率和对口服伊曲康唑有反应的全身性脂溢性皮炎。易感因素如超敏反应和破坏角质化的内科疾病在第7节中进行了综述。
4.4 Malassezia yeasts as components of the cutaneous microbiome 4.4 作为皮肤微生物组组分的马拉色菌酵母菌 The original cutaneous microbiome studies mainly focused on prokaryotic inhabitants; thereafter fungi received more attention in humans and also in dogs and cats.The first large-scale sequencing analysis which evaluated fungal diversity (“mycobiome”) on human skin clearly demonstrated that Malassezia yeasts are the most abundant fungal organisms on many human skin sites, as previously shown for the scalp.In contrast to extensive bacterial diversity found at all human skin sites tested, the fungal diversity seems more site-dependent.Eleven Malassezia species were identified with M. restricta being predominant in the external auditory canal, retroauricular crease and glabella; while M. globosa was on the back, occiput and inguinal crease. The remaining species were detected across other body sites and with lower frequency. Reanalysis of these metagenomic datasets using a more complete set of Malassezia genomes demonstrated the presence of 12 species, with M. restricta and M. globosa by far the most abundant, distantly followed by M. sympodialis. The metagenomic analysis of skin samples from 40 asymptomatic individuals in Hong Kong revealed that 90% of the sequencing reads matched to M. restricta. Another study investigating 40 asymptomatic individuals in Japan indicated that Malassezia population differed by sex, body part and season. Another study reported a significant decrease in community diversity as an indication of skin disease in humans. 最初的皮肤微生物组研究主要集中在原核生物；此后真菌在人类以及犬和猫中受到更多的关注。首次大规模测序分析评价了人类皮肤上的真菌多样性（“真菌生物组”），清楚地表明马拉色菌酵母菌是许多人类皮肤部位上最丰富的真菌生物，如之前头皮所示。与在所有检测的人类皮肤部位发现的广泛细菌多样性相比，真菌多样性似乎更具有位点依赖性。鉴定出 11 种马拉色菌，外耳道、耳后皱褶和眉间以限制马拉色菌为主；而背部、枕骨和腹股沟皱褶为球形马拉色菌。其余种属在其他身体部位检测到，频率较低。使用一组更完整的马拉色菌基因组对这些宏基因组数据集进行再分析，证明存在12个物种，其中限制马拉色菌和球形马拉色菌是迄今为止最丰富的，其次是合轴马拉色菌。对香港40名无症状个体的皮肤样本进行宏基因组分析发现，90%的测序读段与限制马拉色菌匹配。另一项调查日本40例无症状个体的研究表明，马拉色菌人群在性别、身体部位和季节上存在差异。另一项研究报道，作为人类皮肤病指征的群落多样性显著下降。
Only a very few studies examined the skin microbiota in dogs and cats. One study suggested that the main force driving the variability in microbiota composition was the individual, rather than the breed, hair coat or the skin site.Anotherh study used NGS to define a much more diverse cutaneous mycobiota than that previously described with culture-based techniques in studies of healthy and allergic dogs.The cutaneous mycobiota appeared to be influenced by various factors including environmental exposure, cohabitation with other pets and skin health status. Surprising, Malassezia yeasts were not the most abundant fungal organisms on healthy canine skin. Sequences corresponding to filamentous contaminants from the environment (Alternaria, Cladosporium and Epicoccum spp.) were predominant. Furthermore, the same study was unable to detect any significant differences in the relative abundance of Malassezia yeasts between healthy and allergic dogs. In a similar metagenomic analysis performed in healthy and allergic cats, the most abundant fungal sequences were identified as filamentous contaminants from the environment (Cladosporium and Alternaria spp.) and not Malassezia yeasts, which were identified in 30% (35 of 108) and 21% (eight of 39) of healthy and allergic cat samples, but rarely accounted for more than 1% of the relative fungal abundance. 只有极少数研究检查了犬和猫的皮肤微生物群。一项研究表明，驱动微生物群组成变异性的主要力量是个体，而不是品种、被毛或皮肤部位。Anotherh 的研究使用 NGS 来定义一个比以前描述的基于培养的技术在健康和过敏犬的研究中更多样的皮肤真菌生物。皮肤真菌群似乎受到多种因素的影响，包括环境暴露、与其他宠物同居和皮肤健康状况。令人惊讶的是，马拉色菌酵母菌并不是健康犬皮肤上最丰富的真菌微生物。与来自环境的丝状污染物（链格孢属、枝孢属和表球菌属）相对应的序列占主导地位。此外，同一研究无法检测健康犬和过敏犬之间马拉色菌酵母菌相对丰度的任何显著差异。在对健康和过敏猫进行的类似宏基因组分析中，最丰富的真菌序列被鉴定为来自环境的丝状污染物（枝孢属和链格孢属），而不是马拉色菌酵母菌，在30% (35/108) 和 21% (8/39) 的健康和过敏猫样本中被鉴定出，但很少占相对真菌丰度的 1% 以上。
4.5 Conclusions 4.5结论 Malassezia pachydermatis is a normal inhabitant of healthy canine skin and mucosae. Malassezia pachydermatis also predominates in the skin of the domestic cat, although other species are occasionally identified, particularly M. nana in the ear canal and M. slooffiae in the claw fold. Population sizes vary markedly between anatomical sites, and between different breeds. These commensal Malassezia populations provide a reservoir of yeasts that might proliferate and or induce an inflammatory response under the influence of various host predisposing factors. 厚皮马拉色菌是健康犬皮肤和粘膜的正常菌群。厚皮马拉色菌也主要存在于家猫的皮肤中，尽管偶尔也发现其他菌种，特别是耳道中的娜娜马拉色菌和爪皱襞中的斯洛菲马拉色菌。不同解剖部位和不同品种之间的种群规模差异显著。这些共生马拉色菌群提供了一个酵母菌储存库，可能在各种宿主易感因素的影响下增殖和/或诱导炎症反应。
5 Pathogenesis: virulence attributes amongst Malassezia yeasts 5 发病机制：马拉色菌酵母菌中的毒力属性 The interactions between Malassezia yeasts and the skin of their hosts, and the factors which influence transition from commensal to pathogen, are the subject of intensive scientific endeavour, especially pertaining to the common pathogens of humans (M. globosa, M. sympodialis, M. restricta and M. furfur).Comparative genomic studies following the sequencing of 14 Malassezia species have significantly advanced opportunities for understanding of the adaption of the genus to its limited ecological niches (mainly skin), elucidation of virulence attributes necessary for colonisation and infection, and identification of novel interventional targets for therapy. In particular, the novel description of Agrobacterium tumifaciens-mediated transformation systems that allows for the insertion of transfer DNA and targeted gene deletion in M. furfur, M. sympodialis and M. pachydermatis, and thus analysis of individual gene function, is certain to revolutionise our understanding of the biology of this genus. 马拉色菌酵母菌与其宿主皮肤之间的相互作用，以及影响从共生菌向病原菌转化的因素，是科学界努力的课题，尤其是与人类常见病原菌（球形马拉色菌、合轴马拉色菌、限制马拉色菌和糠秕马拉色菌）有关。14 种马拉色菌测序后的比较基因组研究为了解该菌属对其有限生态位（主要是皮肤）的适应性、阐明定植和感染所必需的毒力属性以及鉴定治疗的新型干预性靶标提供了显著的先导机会。特别是，对土壤农杆菌介导的转化系统的新描述，允许在糠秕马拉色菌、合轴马拉色菌和厚皮马拉色菌中插入转移 DNA 和靶向基因缺失，从而分析单个基因功能，肯定会彻底改变我们对该属生物学的认识。
The presence of a nutritionally absorptive fungus within the stratum corneum exposes the host to an array of chemicals, immunogens and allergens, comprising fungal cell wall-associated carbohydrates, proteins and lipids; secreted enzymes that generate both substrates for nutrition and an array of irritant metabolic by-products. The cell wall of Malassezia spp. is unusual in thickness (90– 150 nm), morphology (inner spiralling/corrugation) and composition (predominance of (1→6)- ß-D-glucan, trace of mannan with unusual polysaccharide assembly, chitin prominent in bud-scar, lipidrich wall and capsule ) (Figure 2). Interaction with other commensal microbes might also influence pathogenicity and expression of virulence factors.Thus, these commensal yeasts are likely highly regulated by continuous interactions with the host immune system (Section 6)and these interactions ultimately determine whether the outcome is inflammation (i.e. fungal disease) or not. 角质层内营养吸收真菌的存在使宿主暴露于一系列化学物质、免疫原和过敏原，包括真菌细胞壁相关碳水化合物、蛋白质和脂质；产生营养底物和一系列刺激性代谢副产物的分泌酶。马拉色菌的细胞壁在厚度 (90-150 nm)、形态（内部螺旋/波纹）和组成（主要为 (1→6)-ß-D-葡聚糖、痕量甘露聚糖与异常多糖组装、在芽痕、富含脂质壁和荚膜中突出的甲壳素）方面不常见（图 2）。与其他共生微生物的相互作用也可能影响致病性和毒力因子的表达。因此，这些共生酵母菌可能受到与宿主免疫系统持续相互作用的高度调控（第 6 节），这些相互作用最终决定结局是否为炎症（即真菌病）。
Figure 2. Transmission electron micrograph of Malassezia pachydermatis. Cells have a thick cell wall with characteristic inner spiralling. Monopolar blastic development is associated with a prominent bud scar. Scale bar = 500 nm. 图 2. 厚皮马拉色菌透射电镜照片。
细胞具有较厚的细胞壁，具有特征性的内螺旋。单极母细胞发育与突出的芽痕有关。比例尺 = 500 nm。
Adherence, the specific attachment of the microbe to host cells, is a key step in colonisation and infection of animals by commensal and pathogenic fungi. Adherence of M. pachydermatis to canine corneocytes has been reviewed in detail, and likely involves a small family of proteins that are covalently bound to cell wall carbohydrate and anchored to the plasma membrane. Malassezia cells adhering to keratinocytes have the potential to modulate the expression of an array of cytokines, chemokines and antimicrobial peptides, the outcome of which may be immune-stimulatory (as may occur in disease states, characterised by the development of cutaneous inflammation) or immune-suppressive (promoting commensal carriage) as reviewed. A change in host immunity, altered skin microclimate or disruption in epidermal physiology associated with concurrent diseases (Section 7) may predispose animals to clinical disease. Co-proliferation of staphylococci in the same lesions may exacerbate clinical signs and necessitates concurrent antibacterial therapy in some cases. The term ‘dysbiosis’ has been applied to similar microbial imbalances within the cutaneous microbiome, albeit primarily in the context human and canine atopic dermatitis (cAD). 粘附，即微生物对宿主细胞的特异性粘附，是共生和致病真菌在动物体内定植和感染的关键步骤。厚皮马拉色菌对犬角化细胞的粘附性已被详细综述，可能涉及一个与细胞壁碳水化合物共价结合并锚定在质膜上的蛋白质小家族。粘附于角质形成细胞的马拉色菌细胞有可能调节一系列细胞因子、趋化因子和抗菌肽的表达，其结果可能具有免疫刺激作用（可能发生在疾病状态下，特征为发生皮肤炎症）或免疫抑制（促进共生携带）。宿主免疫力变化、皮肤小气候改变或并发疾病相关的表皮生理学破坏（第7节）可能使动物易患临床疾病。相同病变中的葡萄球菌共增殖可能会加重临床体征，在某些情况下需要同时进行抗菌治疗。术语“微生态失调”已应用于皮肤微生物组内类似的微生物失衡，尽管主要是在人类和犬特应性皮炎 (CAD) 背景下。
The Malassezia genus’ evolution to lipid-dependency is associated with a wide expansion of lipase and phospholipase genes, and loss of carbohydrate metabolism genes, although numbers of secreted proteins overall appear lower than those of related plant pathogens (Section 2). Lipases, highly expressed in the skin of human patients with dandruff and seborrhoeic dermatitis, likely damage the epidermal barrier directly and by hydrolysis of triglycerides. Phospholipase activity in M. pachydermatis is stimulated by the endogenous opioid peptide ß endorphin present in the skin of dogs with dermatoses; activity was significantly higher amongst M. pachydermatis isolates derived from the dogs with otitis externa or skin lesions when compared with those obtained from the dogs with healthy external ears, or non-lesional skin, respectively. Similar observations have been made in pathogenic strains of M. restricta and M. globosa collected from lesions of seborrhoeic dermatitis in humans.Genotypic variants of M. pachydermatis with high phospholipase activity induced higher expression of proinflammatory genes from cultured human keratinocytes. Laboratory data indicated that phospholipase production might act in synergism with biofilm formation (layers of adhering yeasts embedded in variable quantities of extracellular matrix) to induce or exacerbate skin lesions in dogs. By contrast, a secreted aspartyl protease from M. globosa inhibited S. aureus biofilm proliferation and rapidly hydrolysed protein A, a major staphylococcal virulence factor. A correlation between biofilm formation and other virulence factors (hydrophobicity, adherence) was observed amongst 60% of 16 clinical isolates of M. furfur. The role of biofilm formation in potentially reducing susceptibility to antifungal drugs is discussed in Section 10. Other enzymes from Malassezia yeasts such as acid sphin gomyelinases and chitin deacetylases may also influence host-yeast interactions. 马拉色菌属进化为脂质依赖性与脂肪酶和磷脂酶基因的广泛扩增以及碳水化合物代谢基因的丢失有关，尽管分泌蛋白的数量总体上似乎低于相关植物病原体（第2节）。在头皮屑和脂溢性皮炎患者皮肤中高表达的脂肪酶可能通过甘油三酯的水解直接损伤表皮屏障。厚皮马拉色菌中的磷脂酶活性受到皮肤病犬皮肤中存在的内源性阿片肽 ß 内啡肽的刺激；与健康外耳或非病变皮肤犬相比，外耳炎或皮肤病变犬厚皮马拉色菌分离株的活性显著更高。在从人类脂溢性皮炎皮损中采集的限制马拉色菌和球形马拉色菌的致病菌株中也进行了类似的观察。具有高磷脂酶活性的厚皮马拉色菌基因型变体诱导培养的人角质形成细胞促炎基因的较高表达。实验室数据表明，磷脂酶的产生可能与生物膜形成（嵌入不同数量细胞外基质的粘附酵母菌层）协同作用，诱导或加重犬的皮肤病变。相比之下，一种来自球形马拉色菌的分泌型天冬氨酸蛋白酶可抑制金黄色葡萄球菌生物膜增殖，并快速水解蛋白 a，这是一种主要的葡萄球菌毒力因子。在 16 株糠秕马拉色菌临床分离株的60%中观察到生物膜形成与其他毒力因子（疏水性、粘附性）之间的相关性。生物膜形成在潜在降低抗真菌药物敏感性中的作用在第10节中讨论。来自马拉色菌酵母菌的其他酶，如酸性鞘磷脂酶和甲壳素脱乙酰基酶也可能影响宿主-酵母菌的相互作用。
Malassezia yeasts from human skin have the ability to synthesise in vitro a large panel of indolic compounds (mainly malassezin, indolo[3,2-b] carbazole, pityriacitrin, pityrialactone and indirubin) when tryptophan is used as the single nitrogen source. These indoles act as potent ligands for the aryl hydrocarbon receptor (AhR), a nuclear receptor and transcriptional regulator with pleiotropic effects that include down-regulation of immune stimulation, modification of melanogenesis and epidermal cell function, and inhibition of antagonistic microbes. One study suggested that M. pachydermatis is able to induce activation of the AhR in human keratinocytes and to increase the expression of responsive genes and markers of epidermal differentiation.Since indole production was not detected in a study of 80 M. pachydermatis strains from canine otitis externa, AhR activation by M. pachydermatis might be associated with the release of compounds other than indolic metabolites. 人皮肤的马拉色菌酵母菌在以色氨酸为单一氮源时，具有体外合成一大组吲哚类化合物（主要是马拉色菌素、吲哚并 [3，2-b] 咔唑、匹酰肌苷、匹酰内酯和靛玉红）的能力。这些吲哚作为芳香烃受体 (AhR) 的强效配体，AhR 是一种具有多效性作用的核受体和转录调节因子，包括下调免疫刺激、修饰黑色素生成和表皮细胞功能以及抑制拮抗微生物。一项研究表明，厚皮马拉色菌能够诱导人角质形成细胞中 AhR 的活化，并增加应答基因和表皮分化标志物的表达。由于在对来自犬外耳炎的 80 株厚皮马拉色菌菌株的研究中未检测到吲哚生成，厚皮马拉色菌激活 AhR 可能与释放吲哚代谢物以外的化合物有关。
Malassezia cell wall carbohydrates have been longrecognised as IgE binding epitopes in humans with AD while other studies have highlighted their importance in fungal cell recognition by host phagocytic cells. C-type lectins are proteins that bind carbohydrates in a calcium-dependent (hence C) manner via highly-conserved carbohydrate-recognition domains. Langerin, a C-type lectin expressed by Langerhans cells that recognises mannose and beta-glucans, has a strong affinity for Malassezia and Candida spp. and is regarded as a major pattern recognition receptor for both commensal and pathogenic fungi. By contrast, Mincle, a Ctype lectin expressed by activated phagocytes that binds glucosyl and mannosyl-glycolipids from M. pachydermatis and M. sympodialis, selectively recognises Malassezia spp. but not other fungi. In cooperation with Dectin-2, another C-type lectin that recognises a distinct hydrophilic O mannobiose-rich protein, Mincle and Dectin-2 collaborate to enhance production of inflammatory cytokines such as TNF-a, MIP-2 and IL-10 from mouse activated phagocytes exposed to Malassezia furfur. C-type lectin-mediated innate immune mechanisms are discussed further in Section 6. 马拉色菌细胞壁碳水化合物长期以来被认为是特应性皮炎患者的IgE结合表位，而其他研究强调了其在宿主吞噬细胞识别真菌细胞中的重要性。C 型凝集素是通过高度保守的碳水化合物识别结构域以钙依赖性（因此为 C）方式结合碳水化合物的蛋白质。郎格罕细胞凝集素是 郎格罕细胞表达的一种C型凝集素，可识别甘露糖和β-葡聚糖，对马拉色菌和念珠菌有很强的亲和力。并被认为是共生真菌和病原真菌的主要模式识别受体。相比之下，巨噬细胞凝集素是一种由活化的吞噬细胞表达的 C 型凝集素，可结合厚皮马拉色菌和合轴马拉色菌的葡萄糖基和甘露糖基糖脂，选择性识别马拉色菌属。但不包括其他真菌。与另一种 C 型凝集素-树突状细胞凝集素-2（识别一种独特的亲水性富含 O 甘露糖的蛋白质）合作，巨噬细胞凝集素和树突状细胞凝集素-2合作从暴露于糠秕马拉色菌的小鼠活化吞噬细胞中增强炎性细胞因子的产生，如 TNF-a、MIP-2 和 IL-10。C型凝集素介导的先天性免疫机制在第6节中进一步讨论。
5.1 Conclusions 5.1 结论 There have been significant advances in the understanding of the mechanisms of interaction between Malassezia yeasts and their hosts. The outcome of Malassezia growth in the stratum corneum is dependent upon the metabolic activities of the yeasts (expression of cell wall and secreted virulence attributes) and the host’s innate and adaptive immune defensive responses; interactions with other skin commensals (especially staphylococci) may also play a role. All these processes should ideally result in a delicately balanced homeostatic relationship. Further studies are required to define fully the parameters that dictate transitions between commensalism and parasitism that may yield opportunities for novel preventative and therapeutic strategies. 对马拉色菌酵母菌与其宿主相互作用机制的认识有了重大进展。马拉色菌在角质层生长的结果依赖于酵母菌的代谢活动（细胞壁的表达和分泌毒力属性）和宿主的先天和适应性免疫防御反应；与其他皮肤共生菌（尤其是葡萄球菌）的相互作用也可能起一定作用。理想情况下，所有这些过程都应该导致微妙平衡的稳态关系。需要进一步的研究来充分定义决定共生和寄生之间转换的参数，这可能为新的预防和治疗策略提供机会。
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发表于 2022-5-7 16:12:28
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