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铁定的事实:体内转录组学和体外机制研究如何塑造我们对淋病奈瑟菌黏膜感染期间基因调控的理解。

The ironclad truth: how in vivo transcriptomics and in vitro mechanistic studies shape our understanding of Neisseria gonorrhoeae gene regulation during mucosal infection.

作者信息

Moreau Matthew R, Massari Paola, Genco Caroline A

机构信息

Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA 02111, USA.

出版信息

Pathog Dis. 2017 Jul 31;75(5). doi: 10.1093/femspd/ftx057.

DOI:10.1093/femspd/ftx057
PMID:28520925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5808646/
Abstract

Neisseria gonorrhoeae is one of the most prevalent sexually transmitted infections worldwide. This obligate human pathogen has been extensively studied in vitro, where bacterial factors that are known to contribute to gonococcal disease and their regulation are relatively well defined. However, these in vitro experimental conditions only loosely replicate the host specific environment encountered by the bacteria in vivo. We recently reported on the complete gonococcal transcriptome expressed during natural human mucosal infection using RNA-seq analysis. Gene transcripts expressed in vivo (in vivo expressed factors) included genes encoding antibiotic resistance determinants, and a large number of hypothetical genes. A comparison of the gonococcal transcriptome expressed in vivo with the corresponding strain grown in vitro identified sets of genes regulated by infection, including those regulated by iron and the transcriptional regulatory protein Fur. We highlight here the role of Fur and gonococcal-specific regulatory processes important for infection and pathogenicity. We have determined that the genes controlled by Fur follow the same expression pattern in vivo as described previously in vitro, confirming Fur's regulatory role during infection. Collectively, these studies provide new insights into how bacterial fitness and pathogenicity are modulated during human mucosal infection.

摘要

淋病奈瑟菌是全球最常见的性传播感染病原体之一。这种专性人类病原体已在体外进行了广泛研究,已知有助于淋病发病的细菌因子及其调控机制在体外相对明确。然而,这些体外实验条件只是大致模拟了细菌在体内遇到的宿主特异性环境。我们最近利用RNA测序分析报道了在人类自然黏膜感染期间表达的完整淋病奈瑟菌转录组。体内表达的基因转录本(体内表达因子)包括编码抗生素抗性决定因素的基因以及大量假设基因。将体内表达的淋病奈瑟菌转录组与体外培养的相应菌株进行比较,确定了受感染调控的基因集,包括受铁和转录调节蛋白Fur调控的基因。我们在此强调Fur以及对感染和致病性重要的淋病奈瑟菌特异性调控过程的作用。我们已经确定,Fur控制的基因在体内遵循与先前体外描述相同的表达模式,证实了Fur在感染期间的调控作用。总体而言,这些研究为人类黏膜感染期间细菌适应性和致病性的调节提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f71f/5808646/343d12278d9b/ftx057fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f71f/5808646/477ba0f8191a/ftx057fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f71f/5808646/343d12278d9b/ftx057fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f71f/5808646/477ba0f8191a/ftx057fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f71f/5808646/343d12278d9b/ftx057fig3.jpg

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沙眼衣原体和淋病奈瑟菌引起的生殖器外感染:文献综述
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