Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, A Unit of Council of Scientific and Industrial Research (C.S.I.R.), Govt. of India, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata-700 032, India.
Glycobiology. 2010 May;20(5):553-66. doi: 10.1093/glycob/cwp207. Epub 2010 Jan 18.
The presence of different derivatives of sialic acids (SA) on Leishmania donovani instigated us to investigate their status on different strains of Leishmania sp. causing different forms of the disease. Leishmania tropica (K27), Leishmania major (JISH118) and Leishmania mexicana (LV4) responsible for cutaneous, Leishmania braziliensis (L280) and Leishmania amazonensis (LV81) causing diffuse and Leishmania infantum (MON29) responsible for visceral leishmaniasis were included in this study. The strains showed a differential distribution of SA in spite of their close resemblance in pathogenesis. K27, JISH118, L280 and MON29 were categorized as high SA-containing strains having enhanced 9-O-acetyl sialic acid (9-O-AcSA(high)) whereas LV4 and LV81 evidenced considerably reduced SA. Interestingly, 9-O-AcSA(high) promastigotes showed significant viability as compared to their de-O-acetylated forms after exposure to NaNO(2) suggesting the involvement of 9-O-AcSA in conferring nitric oxide (NO) resistance. Enhanced intracellular survivability was demonstrated following infection of human macrophages with 9-O-AcSA(high) promastigotes in contrast to their de-O-acetylated forms indicating their contribution in bestowing a survival benefit. Additionally, reduced accumulation of NO, interleukin-12 and interferon-gamma in the supernatant of macrophages infected with 9-O-AcSA(high) promastigotes indicated suppression of leishmanicidal host responses. However, LV4 and LV81 with least 9-O-AcSA, before and after de-O-acetylation, showed unaltered NO resistance, multiplicity and host responses signifying the probable involvement of other determinants which may be a function of their inherent parasitic attribute. Hence, enhanced levels of 9-O-AcSA serve as one of the potential determinants responsible for increased NO resistance and survivability of parasites by inhibition of host responses.
唾液酸 (SA) 的不同衍生物在利什曼原虫 (Leishmania donovani) 中的存在促使我们研究其在引起不同疾病形式的利什曼原虫属 (Leishmania sp.) 不同菌株中的状态。本研究包括引起皮肤利什曼病的热带利什曼原虫 (K27)、利什曼原虫 (JISH118) 和墨西哥利什曼原虫 (LV4)，引起弥漫性利什曼病的巴西利什曼原虫 (L280) 和亚马逊利什曼原虫 (LV81)，以及引起内脏利什曼病的婴儿利什曼原虫 (MON29)。尽管它们在发病机制上非常相似，但这些菌株表现出 SA 的不同分布。K27、JISH118、L280 和 MON29 被归类为高含 SA 菌株，具有增强的 9-O-乙酰唾液酸 (9-O-AcSA(high))，而 LV4 和 LV81 则表现出明显减少的 SA。有趣的是，9-O-AcSA(high) 前鞭毛体在暴露于 NaNO2 后与去乙酰化形式相比表现出显著的活力，表明 9-O-AcSA 参与了赋予对一氧化氮 (NO) 的抗性。与去乙酰化形式相比，感染高 9-O-AcSA 前鞭毛体的人巨噬细胞中的细胞内存活能力增强表明它们在赋予生存优势方面的贡献。此外，在感染 9-O-AcSA(high) 前鞭毛体的巨噬细胞上清液中 NO、白细胞介素-12 和干扰素-γ的积累减少表明抑制了杀伤性宿主反应。然而，LV4 和 LV81 的 9-O-AcSA 含量最低，在去乙酰化前后，NO 抗性、倍增和宿主反应均未改变，表明可能涉及其他决定因素，这些因素可能是其内在寄生属性的功能。因此，增强的 9-O-AcSA 水平是导致宿主反应抑制、寄生虫增加对 NO 的抗性和存活能力的潜在决定因素之一。
