Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine

Fructose-Asparagine Is a Primary Nutrient during Growth of Salmonella in the Inflamed Intestine
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DOI:
10.1371/journal.ppat.1004209
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发表时间:
2014-06-01
期刊:
影响因子:
6.7
通讯作者:
Ahmer, Brian M. M.
Ahmer, Brian M. M.
中科院分区:
医学1区
文献类型:
--
作者:
Ali, Mohamed M.;Newsom, David L.;Ahmer, Brian M. M.

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鼠伤寒沙门氏菌(沙门氏菌)是影响人类和农业的最重要的食源性病原体之一。我们已经确定,沙门氏菌编码一种新营养素果糖天冬酰胺 (F-Asn) 特有的摄取和利用途径,这对于沙门氏菌在发炎肠道中的健康至关重要(使用无菌、链霉素处理、前无菌人类微生物群和 IL10(-/-) 小鼠进行建模)。仅当沙门氏菌能够引发炎症并使用连四硫酸盐作为无氧呼吸的末端电子受体时,编码 F-Asn 利用的位点 fra 才具有优势(fra 表型分别在沙门氏菌 SPI1(-) SPI2(-) 或 ttrA 突变体中丢失)。沙门氏菌 fra 突变体的严重适应性缺陷表明,F-Asn 是沙门氏菌在发炎肠道中利用的主要营养物质,并且该系统为新疗法提供了有价值的靶点。
Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10(-/-) mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1(-) SPI2(-) or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.