From pathogen to commensal to probiotic: modification of Microbacterium nematophilum-C. elegans interaction during chronic infection by the absence of host insulin signalling

From pathogen to commensal to probiotic: modification of Microbacterium nematophilum-C. elegans interaction during chronic infection by the absence of host insulin signalling
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从病原体到共生菌再到益生菌:嗜线微杆菌-C 的修饰。

DOI:
10.1101/2020.04.01.020933
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发表时间:
2020
期刊:
--
影响因子:
--
通讯作者:
Gravato-Nobre M
Gravato-Nobre M
中科院分区:
--
文献类型:
--
作者:
Gravato-Nobre M

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线虫秀丽线虫以腐烂植被中的微生物为食物来源。为了在富含机会性病原体的环境中生存,线虫进化出一种上皮防御系统,在这种系统中,暴露在表面的组织,如表皮、咽部、肠道、外阴和后肠,能够对急性肠道感染产生适当的免疫防御。然而,目前还不清楚这种蠕虫对慢性肠道感染的反应。为此,我们进行了调查。在慢性感染期间,与炎症、免疫和长寿有关的突变体能找到它们的表型。在自然致病原线虫微杆菌(CBX102菌株)的单一培养中生长的蠕虫寿命和健康时间都会缩短。这与肠道定植无关,因为CBX102和衍生的无毒株UV336都是早期的持久定殖者。相比之下,长寿的daf-2突变体对慢性感染具有抵抗力,表现出较少的定殖率和较高的年龄相关性活力。事实上,UV336起到了益生菌indaf-2的作用,显示出寿命延长超过了OP50。实验室用链球菌种。优雅的文化。在CBX102上生长的daf-2突变体的寿命和活力依赖于FOXO同源基因DAF-16。由于DAF-2/DAF-16轴存在于大多数后生动物中,这表明了一种进化保守的宿主机制,将病原体修改为共生体。
The nematode wormCaenorhabditis elegansdepends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens,C. eleganshas evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyedC. elegansmutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogenMicrobacterium nematophilum(CBX102 strain) had a reduced lifespan and health span. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, long-liveddaf-2mutants were resistant to chronic infection, showing reduced colonisation and a higher age-dependent vigour. In fact, UV336 acted as a probiotic indaf-2, showing a lifespan extension beyond OP50, theE. colistrain used for laboratoryC. elegansculture. Longevity and vigour ofdaf-2mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Since the DAF-2/DAF-16 axis is present in most metazoans this suggests an evolutionary conserved host mechanism to modify a pathogen to a commensal.
DOI: 10.1093/genetics/118.1.75
发表时间: 2002-09
期刊: Genetics
影响因子: 3.3
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发表时间: 2012-04-04
期刊: Cell metabolism
影响因子: 29
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发表时间: 2009
期刊: Proceedings of the National Academy of Sciences
影响因子: --
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