Glucuronic acid confers colonization advantage to enteric pathogens

殖民地化 微生物学 毒力 柠檬酸杆菌 殖民抵抗 病菌 葡萄糖醛酸 生物 寄主(生物学) 毒力因子 胃肠道 细菌 大肠杆菌 生物化学 生态学 基因 遗传学 多糖
作者
Thibaut Rosay,Angel G. Jimenez,Vanessa Sperandio
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [Proceedings of the National Academy of Sciences]
卷期号:121 (13)
标识
DOI:10.1073/pnas.2400226121
摘要

Glucuronidation is a detoxification process to eliminate endo- and xeno-biotics and neurotransmitters from the host circulation. Glucuronosyltransferase binds these compounds to glucuronic acid (GlcA), deactivating them and allowing their elimination through the gastrointestinal (GI) tract. However, the microbiota produces β-glucuronidases that release GlcA and reactivate these compounds. Enteric pathogens such as enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium sense and utilize galacturonic acid (GalA), an isomer of GlcA, to outcompete the microbiota promoting gut colonization. However, the role of GlcA in pathogen colonization has not been explored. Here, we show that treatment of mice with a microbial β-glucuronidase inhibitor (GUSi) decreased C. rodentium ’s colonization of the GI tract, without modulating bacterial virulence or host inflammation. Metagenomic studies indicated that GUSi did not change the composition of the intestinal microbiota in these animals. GlcA confers an advantage for pathogen expansion through its utilization as a carbon source. Congruently mutants unable to catabolize GlcA depict lower GI colonization compared to wild type and are not sensitive to GUSi. Germfree mice colonized with a commensal E. coli deficient for β-glucuronidase production led to a decrease of C. rodentium tissue colonization, compared to animals monocolonized with an E. coli proficient for production of this enzyme. GlcA is not sensed as a signal and doesn’t activate virulence expression but is used as a metabolite. Because pathogens can use GlcA to promote their colonization, inhibitors of microbial β-glucuronidases could be a unique therapeutic against enteric infections without disturbing the host or microbiota physiology.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
夏惋清完成签到 ,获得积分0
刚刚
1秒前
CodeCraft应助科研通管家采纳,获得10
1秒前
共享精神应助科研通管家采纳,获得10
1秒前
余九应助科研通管家采纳,获得10
1秒前
Lucas应助科研通管家采纳,获得10
1秒前
星辰大海应助科研通管家采纳,获得10
1秒前
Owen应助科研通管家采纳,获得10
1秒前
orixero应助科研通管家采纳,获得10
1秒前
FIN应助科研通管家采纳,获得10
1秒前
田様应助科研通管家采纳,获得10
1秒前
CodeCraft应助灵犀采纳,获得10
2秒前
NexusExplorer应助DAKE采纳,获得10
2秒前
2秒前
ChouNen发布了新的文献求助10
3秒前
xiaoyao发布了新的文献求助30
5秒前
7秒前
Lucas应助苗条的静白采纳,获得30
8秒前
Can完成签到,获得积分10
8秒前
可耐的葶发布了新的文献求助10
9秒前
共享精神应助颜林林采纳,获得10
9秒前
10秒前
chanyed完成签到 ,获得积分10
10秒前
11秒前
xiaoyao完成签到,获得积分10
12秒前
今时今日完成签到,获得积分20
13秒前
顺利书翠发布了新的文献求助10
14秒前
沉静的十八完成签到,获得积分10
15秒前
16秒前
17秒前
无限雨南发布了新的文献求助10
17秒前
Hello应助今时今日采纳,获得10
18秒前
灵犀发布了新的文献求助10
20秒前
李瑞卿完成签到 ,获得积分10
20秒前
wmdpyxnz发布了新的文献求助10
22秒前
852应助自由思枫采纳,获得10
22秒前
纯真以晴发布了新的文献求助30
25秒前
26秒前
ChouNen发布了新的文献求助10
30秒前
30秒前
高分求助中
Manual of Clinical Microbiology, 4 Volume Set (ASM Books) 13th Edition 1000
Sport in der Antike 800
De arte gymnastica. The art of gymnastics 600
Berns Ziesemer - Maos deutscher Topagent: Wie China die Bundesrepublik eroberte 500
Stephen R. Mackinnon - Chen Hansheng: China’s Last Romantic Revolutionary (2023) 500
Sport in der Antike Hardcover – March 1, 2015 500
Boris Pesce - Gli impiegati della Fiat dal 1955 al 1999 un percorso nella memoria 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2423211
求助须知:如何正确求助?哪些是违规求助? 2111984
关于积分的说明 5348068
捐赠科研通 1839497
什么是DOI,文献DOI怎么找? 915686
版权声明 561258
科研通“疑难数据库(出版商)”最低求助积分说明 489747