Uncovering the Role of Small RNAs in Staphylococcus aureus Infections Using Human-Derived RNA Sequencing Data

Description du projet

Le rôle des petits ARN régulateurs dans les infections à Staphylococcus aureus

Le Staphylococcus aureus est à l’origine de maladies pouvant entraîner des infections très graves. Le traitement de cette infection est complexe, en raison de ses souches hautement virulentes et résistantes aux antibiotiques, notamment MRSA, VRSA et VISA. La virulence et la résistance de cet agent pathogène sont en partie régulées par des petits ARN (sRNA). Cependant, leur rôle dans les infections humaines n’est pas clair en raison du manque d’études menées dans des conditions physiologiques réalistes. Soutenu par le programme Actions Marie Skłodowska-Curie, le projet URSRA va s’appuyer des données de séquençage d’ARN issues d’échantillons humains pour identifier et caractériser les sRNA. Il entend révéler des sARN inconnus liés à la virulence et à la résistance aux antibiotiques de Staphylococcus aureus, ce qui, à terme, améliorera notre compréhension de sa pathogenèse et ouvrira la voie à de nouvelles stratégies thérapeutiques.

Objectif

Staphylococcus aureus is a major human pathogen responsible for a wide range of infections, from mild skin abscesses to lifethreatening conditions such as sepsis, endocarditis, and pneumonia. It colonizes about a third of the human population and can cause infections in both hospital settings and the community. The emergence of antibiotic-resistant strains, particularly methicillinresistant S. aureus (MRSA), complicates treatment and increases healthcare costs. Alarmingly, vancomycin-resistant S. aureus (VRSA) and vancomycin-intermediate resistant S. aureus (VISA) have also been reported, leading to more severe infections and longer treatment durations.
The success of S. aureus as a pathogen is largely due to its wide array of virulence factors and its ability to develop antibiotic resistance. Regulation of these critical functions occurs at both transcriptional and post-transcriptional levels, involving mechanisms such as small-RNAs (sRNAs). sRNAs are small regulatory molecules that can quickly modulate gene expression by binding to messenger RNAs (mRNAs). Despite their potential significance, the role of sRNAs in S. aureus virulence and antibiotic resistance during human infection remains poorly understood. Most existing studies have been conducted under in vitro conditions that do not accurately mimic human physiological environments.
To address this knowledge gap, we propose to use RNA sequencing data from human-derived samples to identify and characterize sRNAs that are important during human infection. This approach will provide a more accurate representation of sRNA expression and function in vivo. We aim to uncover previously undiscovered sRNAs that contribute to the virulence and antibiotic resistance of S. aureus. Our findings will enhance the understanding of S. aureus pathogenesis and inform the development of novel therapeutic strategies to combat this pathogen.