Infectious Diseases and Whole-Genome Sequencing:The “One Day in Denmark” project

Infectious diseases are responsible for approximately 15% of all deaths worldwide. From the more than one thousand organisms able to cause human disease identified so far, 38% correspond to bacteria. Although bacterial species are intrinsically resistant to particular antimicrobial agents, they are able to acquire and transmit new mechanisms of resistance to drugs that have, in the past, been effective for treatment. This acquisition and dissemination of new antimicrobial resistance (AMR) mechanisms is currently one the of most concerning public health threats, not only due to the depletion of effective antimicrobial agents but also due to the more severe outcomes of infections caused by resistant organisms, when compared with their susceptible counterparts. In clinical microbiology laboratories different diagnostics methods are used to characterize these organisms. Species identification, antimicrobial susceptibility testing and typing are frequently performed, either through phenotypic methods or molecular methods. These methods vary in cost, turnover time, accuracy and discriminatory power. Whole-genome sequencing (WGS) technologies are a promising diagnostics tool due to the large amount of data produced by one single laboratory protocol, which can be analysed to completely characterize bacterial isolates, instead of the multiple routine protocols currently in place. The increase of sequencing accuracy, decrease in cost and improvement of bioinformatics tools and databases make the application of these technologies in clinical settings a possibility, but there are still significant gaps in research impeding their implementation. The most important shortcoming of current literature is that the majority of benchmarking and comparative studies only focus on pre-selected bacterial taxa, thus not truly reflecting the variety of organisms processed in clinical settings. The main aim of this PhD project and thesis was to resolve that important gap in scientific knowledge through the comparison of routine ...