Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri.
Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri.
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DOI：
10.1186/s12915-021-01078-1
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发表时间：
2021-07-22
期刊：
影响因子：
5.4
通讯作者：
Dacks JB
中科院分区：
文献类型：
--
作者：
Herman EK;Greninger A;van der Giezen M;Ginger ML;Ramirez-Macias I;Miller HC;Morgan MJ;Tsaousis AD;Velle K;Vargová R;Záhonová K;Najle SR;MacIntyre G;Muller N;Wittwer M;Zysset-Burri DC;Eliáš M;Slamovits CH;Weirauch MT;Fritz-Laylin L;Marciano-Cabral F;Puzon GJ;Walsh T;Chiu C;Dacks JB
机会性病原体福氏奈格勒菌在人类大脑中建立了感染，几乎总是在两周内死亡。阿米巴对大脑物质进行片状摄取，或称巨噬细胞增多症，导致直接组织损伤和大规模炎症。Fowleri与其他非致病的Naegleria物种的区别的细胞学基础尚不清楚。然而，随着福氏新城疫病原体地理范围的扩大，可能是由于气候变化，了解这种病原体是如何入侵和杀死的既重要又及时。在这里，我们报告了一种从系统水平上理解鸡奈瑟氏菌生物学和感染的组学方法。我们对两个新的福勒氏杆菌菌株进行了测序，并对在小鼠感染模型中培养的低致病性和高致病性福勒氏杆菌进行了转录分析。比较分析提供了对菌株之间编码的蛋白质互补的深入评估，发现高度保守。对多种不同细胞系统的分子进化分析表明，福氏新月球藻基因组编码的完整细胞谱与自由生活的格氏新月球藻相似。从转录组学来看，无论是胁迫反应还是侧向基因转移所产生的性状都不是致病性的关键。相比之下，细胞系统，如蛋白酶、溶酶体机械和运动性，以及代谢重新编程和新的N.Fowleri蛋白，都与促进宿主内的致病有关。在小鼠传代的N.Fowleri中，与谷氨酸代谢和氨运输相关的基因表达上调，表明适应了中枢神经系统中可用的碳源。对Naegleria基因组和转录本的深入分析提供了一个参与机会性致病的细胞系统模型，揭示了理解一种罕见但高度致命的病原体的生物学的新角度。网上版载有补充材料，可在10.1186/s12915-021-01078-1查阅。
The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen. The online version contains supplementary material available at 10.1186/s12915-021-01078-1.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.7
作者：
Minh BQ;Nguyen MA;von Haeseler A
通讯作者：
von Haeseler A
影响因子：
2.1
作者：
ALDAPE, K;HUIZINGA, H;MCKERROW, J
通讯作者：
MCKERROW, J
影响因子：
11.8
作者：
Cope, Jennifer R.;Conrad, Dennis A.;Visvesvara, Govinda S.
通讯作者：
Visvesvara, Govinda S.
影响因子：
3.8
作者：
Debnath, Anjan;Calvet, Claudia M;Podust, Larissa M
通讯作者：
Podust, Larissa M