Impact of zinc and zinc transporters in Mycobacterium avium ssp. paratuberculosis pathogenicity

鸟分枝杆菌亚种中锌和锌转运蛋白的影响。

• 批准号: 280903739
• 负责人: Professor Dr. Ralph Goethe
• 金额: --
• 依托单位: Institut für Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/280903739?language=en
• 关键词: Impact; zinc; transporters; Mycobacterium; avium

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease (JD, paratuberculosis), a chronic, granulomatous enteritis in ruminants. JD is one of the most widespread bacterial diseases of animal husbandry with significant economic impact. However, pathobiology of MAP is largely unresolved. In our studies, we aimed to clarify differences in MAP pathobiology to other mycobacteria by comparison of MAP with the closely related Mycobacterium avium ssp. or nonpathogenic mycobacteria. Our recent deep sequencing analysis of RNA from MAP cultures after zinc starvation revealed that 70 genes responded to zinc limitation. Remarkably, 45 of these genes were located on a large genomic island (ZnGI) of approximately 90 kb which included the two MAP specific long sequence polymorphisms LSP14 and LSP15. Thirty-five of these genes were predicted to be controlled by the major transcriptional regulator for zinc, FurB. This clustering of zinc responsive genes was exclusively found in MAP and not in other mycobacteria. Furthermore, in contrast to other mycobacteria, MAP possesses three putative zinc transporters, of which two are unique to MAP and possibly acquired via horizontal gene transfer. For one of the transporters, MptABC, a FurB dependent regulation was demonstrated. Thus, zinc seems to play an important role in the metabolism of MAP. This particular aspect might be of main importance for disease progression of JD in ruminants as MAP induced inflammation is most frequently found in the distal ileum, the major site of zinc absorption of the host. The project aims to identify the relevance of zinc and zinc transporters for MAP metabolism and pathobiology.

鸟分枝杆菌副结核亚种（MAP）是约内氏病（JD，副结核）的病原体，约内氏病是反刍动物的一种慢性肉芽肿性肠炎。JD是畜牧业最普遍的细菌性疾病之一，具有重大的经济影响。然而，MAP的病理生物学在很大程度上尚未解决。在我们的研究中，我们旨在通过比较MAP与密切相关的鸟分枝杆菌亚种，阐明MAP与其他分枝杆菌的病理生物学差异。或非致病性分枝杆菌。我们最近对锌饥饿后MAP培养物的RNA进行了深度测序分析，发现有70个基因对锌限制做出了反应。值得注意的是，这些基因中有45个位于约90 kb的大基因组岛（ZnGI）上，其中包括两个MAP特异性长序列多态性LSP14和LSP15。这些基因中有35个被预测是由锌的主要转录调节因子FurB控制的。这种锌反应基因的聚集只在MAP中发现，而在其他分枝杆菌中没有发现。此外，与其他分枝杆菌相比，MAP具有三种推定的锌转运蛋白，其中两种是MAP所特有的，可能通过水平基因转移获得。对于其中一种转运蛋白MptABC，证明了FurB依赖性调节。因此，锌似乎在MAP的代谢中起重要作用。这一特定方面可能对反刍动物JD的疾病进展具有重要意义，因为MAP诱导的炎症最常见于回肠远端，这是宿主吸收锌的主要部位。该项目旨在确定锌和锌转运蛋白与MAP代谢和病理学的相关性。