The RyfA small RNA regulates oxidative and osmotic stress responses and virulence in uropathogenic Escherichia coli.
The RyfA small RNA regulates oxidative and osmotic stress responses and virulence in uropathogenic Escherichia coli.
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DOI：
10.1371/journal.ppat.1009617
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发表时间：
2021-05
期刊：
影响因子：
6.7
通讯作者：
Dozois CM
中科院分区：
文献类型：
--
作者：
Bessaiah H;Pokharel P;Loucif H;Kulbay M;Sasseville C;Habouria H;Houle S;Bernier J;Massé É;Van Grevenynghe J;Dozois CM
尿路感染（UTIs）是人类常见的细菌感染性疾病，而尿路致病性大肠杆菌（UPEC）菌株是引起尿路感染的最常见原因。在感染期间，UPEC必须应对尿路中的各种压力条件。在这里，我们证明了UPEC菌株的小RNA (sRNA) RyfA是抵抗氧化和渗透胁迫所必需的。对ryfA突变体的转录组学分析显示，与一般应激反应、代谢、生物膜形成和细胞表面蛋白编码基因相关的基因表达发生了变化。UPEC菌株CFT073中ryfA的失活减少了小鼠尿路定植，ryfA突变体也减少了1型和P型菌毛（毛）的产生，这两种粘连素已知对UTI很重要。此外，ryfA的缺失也降低了人巨噬细胞的UPEC存活。因此，ryfA在UPEC对应激的适应中起着关键的调节作用，这有助于巨噬细胞的UTI和存活。小调控rna在细菌适应、生理和代谢中起着关键作用。我们通过遗传学、分子和细胞培养方法以及小鼠感染模型研究了小RNA ryfA在尿路致病性大肠杆菌中的作用。我们证明RyfA对抵抗氧化和渗透胁迫很重要，并影响多种应激反应的全局转录。ryfA的缺失也减少了1型和P型菌毛（毛）的产生，并增加了游泳的运动性。RyfA也在小鼠尿路感染（UTI）模型和人原代巨噬细胞和细胞系的存活中发挥重要作用。阐明RyfA在适应应激反应和毒力中的作用，有助于深入了解致病性大肠杆菌和其他肠杆菌毒力的重要新调控机制，这可能导致针对这些病原体的靶向治疗或预防方法的发展。
Urinary tract infections (UTIs) are a common bacterial infectious disease in humans, and strains of uropathogenic Escherichia coli (UPEC) are the most frequent cause of UTIs. During infection, UPEC must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrate that the small RNA (sRNA) RyfA of UPEC strains is required for resistance to oxidative and osmotic stresses. Transcriptomic analysis of the ryfA mutant showed changes in expression of genes associated with general stress responses, metabolism, biofilm formation and genes coding for cell surface proteins. Inactivation of ryfA in UPEC strain CFT073 decreased urinary tract colonization in mice and the ryfA mutant also had reduced production of type 1 and P fimbriae (pili), adhesins which are known to be important for UTI. Furthermore, loss of ryfA also reduced UPEC survival in human macrophages. Thus, ryfA plays a key regulatory role in UPEC adaptation to stress, which contributes to UTI and survival in macrophages. Small regulatory RNAs play a critical role in bacterial adaptation, physiology, and metabolism. We investigated the role of the small RNA ryfA in uropathogenic E. coli, by using genetic, molecular and cell culture approaches, and mouse infection models. We demon-strate that RyfA is important for resistance to oxidative and osmotic stresses and affects the global transcription of multiple responses to stress. Deletion of ryfA also reduced production of type 1 and P fimbriae (pili) and increased swimming motility. RyfA also plays an important role in urinary tract infection (UTI) in the mouse model and for survival in human primary macrophages and cell lines. Elucidating a role for RyfA in adaptation to stress response and virulence provides insight into new regulatory mechanisms important for virulence in pathogenic E. coli and likely other Enterobacteria that may lead to development of targeted therapeutic or prophylactic approaches against these pathogens.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
5.7
作者：
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3.2
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影响因子：
3.1
作者：
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通讯作者：
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作者：
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