miRs4Staph · Functional high-throughput analysis of the role of microRNAs in regulating Staphylococcus aureus infection
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-10-15 → 2022-10-14
- EU contribution
- €147,815
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Functional high-throughput analysis of the role of microRNAs in regulating Staphylococcus aureus infection
Staphylococcus aureus is a bacterium commonly found on the skin and nares of both humans and animals. However, it can become an opportunistic pathogen, causing a variety of clinical manifestations, from minor skin infections to life-threatening diseases, including pneumonia, osteomyelitis and endocarditis. The treatment of S. aureus infections has become increasingly difficult due to the emergence of antibiotic-resistant strains in clinical context and the spreading of these strains in the community. Nowadays, it is known that S. aureus can live inside host cells and this intracellular lifestyle is crucial for infection dissemination and persistence. Also, intracellular bacteria may be protected from the activity of antimicrobials, leading to treatment failure and post-therapy relapse. In order to successfully invade and survive inside host cells, S. aureus needs to modulate host cell functions through several mechanisms. MiRNAs are small molecules present in host cells, which are capable of regulating cellular gene expression and, thus, influence the outcome of S. aureus infection. In this context, the goal of this study was to discover miRNAs that regulate S. aureus invasion, survival, and replication within host cells. The knowledge of these factors may potentially reveal novel therapeutical targets to control S. aureus infection.
Data: CORDIS, © European Union
Project objective
Staphylococcus aureus is an opportunistic bacterial pathogen that causes acute and chronic infections responsible for a broad spectrum of human diseases. The high prevalence of antibiotic-resistant strains in clinical context and the spreading of these strains in the community, make S. aureus infections a leading cause of morbidity and mortality in developed countries. A better understanding of the factors contributing to bacteria resistance and host-pathogen interaction is essential to counteract S. aureus infection and, ultimately, to develop more effective therapeutic approaches. MicroRNAs (miRNAs) are genome-encoded small non-coding RNAs, which play a pervasive role in the post-transcriptional control of eukaryotic gene expression. Emerging evidence supports a determinant role for miRNAs in the interplay between bacterial pathogens and host cells, as part of the immune response, or as a molecular strategy exploited by pathogens to subvert host cellular functions. However, a comprehensive analysis of host miRNAs function during infection by S. aureus is still missing.The main goal of this project is to identify and characterize host miRNAs, which are critical for S. aureus-host interaction at the cellular level. This will be achieved through interdisciplinary and innovative strategies, such as large-scale genome-wide miRNAs screenings and high-content analysis. To increase the biological relevance of the study, the effect of selected miRNAs will be validated in S. aureus clinical isolates obtained from osteomyelitis patients. The identification and characterization of miRNA molecular targets will be based on computational and experimental approaches. Through the application of cutting-edge techniques, this project will reveal previously unappreciated factors/pathways essential for S. aureus infection, providing insights into the complex host-pathogen interplay. Additionally, the identified novel factors/pathways may be explored for therapeutic intervention.
Original text from CORDIS.
Participants
- CENTRO DE NEUROCIENCIAS E BIOLOGIACELULAR ASSOCIACAO · COIMBRACoordinatorPortugal
Links
Data: CORDIS, © European Union