Bioinformatics, the study of biological data using various computational techniques, is a very important aspect of biology, and its integration would greatly benefit current high school curricula. However, because most bioinformatics tools have not been readily accessible until recently, most high school instructors were not exposed to them during their formative years. We describe a bioinformatics-based module that introduces the application of genome comparison in the identification of “pathogenic islands.” The module also introduces foundational concepts of horizontal gene transfer and the genetic basis of virulence, with a special focus on antibiotic resistance – a theme teachers and students alike can easily connect and relate to. The module takes students on a journey: from conceptualizing the perfect pathogen, to an immersive experience of being a pathogen, and finally the experience of being a research scientist identifying drug-resistant genes and other virulence factors using the bioinformatics tool of genome comparison.