H2020Индивидуална стипендия2018–2020

SaRNAReg · Staphylococcus aureus sRNA targetomes and regulatory networks involved in fast adaptive responses: structure, mechanisms and dynamics

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-06-04 → 2020-06-03
Финансиране от ЕС: 174 752 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Малките регулаторни РНК при бактерията Staphylococcus aureus контролират синтеза на токсини и протеини, чрез които тя атакува организма. Разбирането на тези мрежи помага да се разбере как бактерията се адаптира и причинява инфекции, особено при резистентните към лекарства щамове.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Staphylococcus aureus sRNA targetomes and regulatory networks involved in fast adaptive responses: structure, mechanisms and dynamics

Although Staphylococcus aureus is a commensal bacterium of the human nose and skin, this opportunistic pathogen is responsible for a wide range of nosocomial and community-acquired infections. Due to the worldwide spread of hypervirulent multidrug-resistant strains, S. aureus infections are now considered as a major health issue. S. aureus has developed many strategies to regulate the synthesis of its various and redundant virulence factors in response to host and perceived stresses. These networks are coordinated by complex interactions between numerous two-component systems, transcription factors, and small regulatory RNAs (sRNAs). Since their discovery in the early 1980’s, accumulated results depict sRNAs as key actors in all aspect of bacterial physiology. Described as 50 to 500 nt-long RNA fragments, sRNAs generally form short and imperfect pairings with their target mRNAs, thus regulating their translation and/or stability. This limited complementarity enables them to modulate the expression of multiple mRNAs, forming their interactome. By directly targeting mRNAs, sRNA-dependent regulation provides a rapid and specific reprogramming of gene expression according to changing physiological conditions. Remarkably, several staphylococcal sRNAs are described as key virulence regulators. For instance, RNAIII is part of a regulatory network controlling the expression of numerous virulence factors such as cell surface proteins, exoproteins and toxins required for host immune evasion and survival. Hundreds of S. aureus sRNAs have been identified but little to no targets are known. Indeed, the identification of mRNA targets remains one of the biggest challenges in the sRNA field. The main goal of SaRNAReg project is to draw a comprehensive regulatory network of small RNAs involved in virulence and stress responses in S. aureus. This should notably bring the missing information to better understand the mechanisms of S. aureus survival and the existing relationships between virulence, metabolism adaptation, and stress responses.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Staphylococcus aureus is an opportunistic human pathogen responsible for severe nosocomial and community acquired infections. S. aureus has evolved a large number of strategies to regulate the synthesis of multiple virulence factors including the use of small regulatory RNAs (sRNAs). These sRNAs in combination with transcriptional regulators adapt cell growth in response to various stresses and environmental conditions. Hence, the identification of sRNAs regulatory networks is of crucial importance in the fight against emerging multidrug resistant strains. Using recent and innovative technologies (i.e. MS2-affinity purification coupled with RNA sequencing and ribosome profiling), we will investigate biological roles of sRNAs, elucidate their targetomes, and their mechanisms of action that was not possible to obtain with classical genetic and biochemical approaches. This project is aimed to draw comprehensive sRNA regulatory networks, which may contain many new targets regulated by unexpected mechanisms and unravel the deepest mysteries in sRNA field in this major opportunistic pathogen. Finally, sRNA-mediated regulation dynamics will be analyzed with unprecedented scrutiny in single-cell studies. The recent development of techniques to visualize RNA and to monitor gene expression in individual bacterium, offer the possibility to address specific questions related to the dynamics of sRNA regulation. Proposed single cell studies will be crucial to investigate the dynamics of sRNAs-dependent regulation, but also to monitor its impact on a monoclonal population behavior in response to a particular stress. Such analysis will open long term perspectives such as to monitor the influence of the microbiome on S. aureus physiology. It should also pave the way to the identification of novel targets for drug design and to the development of novel antimicrobial compounds. New findings will be commercially exploited through patenting and licensing before publications.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция