Carbapenem resistance in Enterobacteriaceae: diagnostic value of the small RNA landscapes

Carbapenem resistant Enterobacteriaceae (CRE) are one of the most important threats to the global public health today. In Ecuador, we currently face severe outbreaks of CRE infections but rapid responsiveness of the hospital laboratories is hampered by the lack of good diagnostics to detect CREs. Previous studies have shown that the small RNAs play a crucial role in the bacterial responses to changing conditions, such as antibiotic pressure. In this PhD project, I will profile the sRNA landscapes of carbapenem resistant and sensitive Enterobacteriaceae and translate specific sRNA markers into new CRE diagnostics. I will start with assessing the prevalence of CREs in nosocomial and systemic infections at two hospitals in Quito. I will generate a “CRE” biobank with clinical samples from patients with carbapenem resistant and sensitive bacteria. In a next phase, I will profile the sRNA landscapes of CRE isolates versus non-CRE isolates using state-of-the-art RNA sequencing techniques, select suitable sRNA biomarkers for CRE phenotypes and validate them in the CRE biobank. Finally, I will develop sRNA based diagnostics and evaluate the new tests in target populations in Ecuador. This project will be the first one that investigates the sRNA landscapes in CRE and will deliver the first RNA diagnostics for rapid detection of CRE in clinical samples. Importantly, this work will also provide the first insights in the role of sRNAs in carbapenem resistance mechanisms.

Project type:PhD project