The Good, the Bad and the Deadly: Characterisation of bacteria through DNA analysis

Sixty years have passed from the discovery of the DNA's double helix structure, and at the time it would have been impossible to imagine that today we could receive our own DNA with information about our ancestors, or potential diseases we could get, based on the analysis of the DNA sequences. High-throughput DNA sequencing started a revolution, which is still ongoing, in biology and medicine, bringing new ways of studying diseases that could not have been possible before.

Millions of people die every year from bacterial infections, and given the trends toward globalization of travel and commerce, with urbanization and an aging population, infectious diseases are coming back as a possible global threat. At present thousands of completely sequenced bacteria are publicly available, with many hundreds of genomes completed every year, also due to the constantly decreasing costs for sequencing a bacterial isolate.

Using this invaluable data, scientists are bringing a revolution in the way clinical microbiology is done and in the way infectious diseases are diagnosed and treated. My PhD project focused on the use of Bacterial Whole Genome Sequence (WGS) data for the prediction of pathogenic features, and the identification of bacterial species and subtypes, as well as phenotypic traits like antibiotic resistance.

The thesis starts with an introduction to the problems related to infectious diseases, as well as the history of DNA, DNA sequencing and its application in clinical microbiology are overviewed. The thesis continues with three chapters and concludes with a discussion on possible future applications of DNA sequence data in clinical and public health microbiology.

Chapter one introduces the challenges related to the use of WGS for the prediction of bacterial pathogenicity features. The manuscript included in this chapter describes a prediction method for bacterial pathogenicity, which was also the main topic of my PhD studies. Chapter two introduces the possibility to identify bacterial species and subtypes through DNA sequence analysis and includes two manuscripts about this topic.

In chapter three the problem of antibiotic resistance is discussed and a manuscript describing a method for identifying antimicrobial resistant genes from bacterial WGS data is included. The thesis terminates with a discussion on the possible future applications of sequencing technologies in clinical and public health microbiology.