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鞘孢菌/拟青霉复合群中的糖缀合物和多糖:结构特征、在细胞分化、细胞识别和毒力中的作用。

Glycoconjugates and polysaccharides from the Scedosporium/Pseudallescheria boydii complex: structural characterisation, involvement in cell differentiation, cell recognition and virulence.

机构信息

Departamento de Microbiologia Geral, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Brasil.

出版信息

Mycoses. 2011 Oct;54 Suppl 3:28-36. doi: 10.1111/j.1439-0507.2011.02105.x.

Abstract

Peptidorhamnomannans (PRMs), rhamnomannans and α-glucans are especially relevant for the architecture of the Scedosporium/Pseudallescheria boydii cell wall, but many of them are immunologically active, with great potential as regulators of pathogenesis and the immune response of the host. In addition, some of them can be specifically recognised by antibodies from the sera of patients, suggesting that they could also be useful in diagnosis of fungal infections. Their primary structures have been determined, based on a combination of techniques including gas chromatography, electrospray ionization - mass spectrometry (ESI-MS), (1)H-COSY and TOCSY, (13)C and (1)H/(13)C NMR spectroscopy. Using monoclonal antibodies to PRM, we showed that it is involved in germination and viability of P. boydii conidia, in the phagocytosis of P. boydii conidia by macrophages and non-phagocytic cells and in the survival of mice with P. boydii infection. Also, components of the fungal cell wall, such as α-glucans, are involved. Rhamnomannans are immunostimulatory and participate in the recognition and uptake of fungal cells by the immune system. These glycosylated polymers, being present in the fungal cell wall, are mostly absent from mammalian cells, and are excellent targets for the design of new agents capable of inhibiting fungal growth and differentiation of pathogens.

摘要

肽鼠李甘露聚糖(PRM)、鼠李甘露聚糖和α-葡聚糖对于棘孢木霉/拟青霉细胞壁的结构特别重要,但其中许多物质具有免疫活性,具有调节发病机制和宿主免疫反应的巨大潜力。此外,其中一些物质可以被来自患者血清的抗体特异性识别,这表明它们也可能有助于真菌感染的诊断。它们的一级结构已经确定,这是基于包括气相色谱、电喷雾电离-质谱(ESI-MS)、(1)H-COSY 和 TOCSY、(13)C 和(1)H/(13)C NMR 光谱在内的多种技术的组合。我们使用针对 PRM 的单克隆抗体表明,它参与棘孢木霉分生孢子的萌发和活力、棘孢木霉分生孢子被巨噬细胞和非吞噬细胞吞噬以及感染棘孢木霉的小鼠的存活。此外,真菌细胞壁的成分,如α-葡聚糖,也参与其中。鼠李甘露聚糖具有免疫刺激作用,并参与免疫系统对真菌细胞的识别和摄取。这些糖基化聚合物存在于真菌细胞壁中,而在哺乳动物细胞中则很少存在,是设计能够抑制真菌生长和病原体分化的新型药物的绝佳靶点。

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