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

Descrizione del progetto

Il ruolo dei piccoli RNA regolatori nelle infezioni da Staphylococcus aureus

Lo Staphylococcus aureus provoca malattie che possono determinare la comparsa di infezioni molto gravi; il trattamento di tali infezioni non è semplice, poiché comprende ceppi altamente virulenti e resistenti agli antibiotici tra cui MRSA, VRSA e VISA. La virulenza e la resistenza dell’agente patogeno sono regolate in parte dai piccoli RNA (sRNA); ciononostante, il loro ruolo nelle infezioni umane è tuttora poco chiaro a causa della mancanza di studi condotti in condizioni fisiologiche realistiche. Sostenuto dal programma di azioni Marie Skłodowska-Curie, il progetto URSRA mira a utilizzare i dati di sequenziamento dell’RNA provenienti da campioni umani per identificare e caratterizzare gli sRNA, consentendo di scoprirne di finora sconosciuti legati alla virulenza e alla resistenza agli antibiotici dello Staphylococcus aureus e migliorando in ultima analisi la nostra comprensione in merito alla sua patogenesi, nonché fornendo le basi per lo sviluppo di nuove strategie terapeutiche.

Obiettivo

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.