The host can be thought of as a growth medium for bacteria (Brown et al. 2008). Within the host, the availability of nutrients and the presence of immune system stressors is complex and dynamic. However, there is an incomplete understanding of how the host environment influences the ability of bacteria to grow and cause disease. One way that we are investigating this question is by using RNA-seq and machine-learning strategies to characterize the core gene expression profile of Pseudomonas aeruginosa in various human, mouse, and in vitro conditions. We are also using transposon insertion sequencing (Tn-Seq) and transgenic knock-out mice to explore how predisposing conditions, like diabetes, determine which genes P. aeruginosa requires to cause chronic wound infections. Finally, we are using Tn-Seq to examine how the site of infection (such as chronic wound, abscess, and osteomyelitis) determines which genes are essential for Staphylococcus aureus to cause infection (Ibberson et al. 2017). Ultimately, we aim to improve our understanding of how the host environment impacts the physiology of pathogenic bacteria.