A genetic study of an outbreak of Enterococcus faecalis - a leading cause of drug-resistant bacterial infections - in a hospital has revealed how the organism became resistant to new antibiotics and adapted to infect the human bloodstream. The research sheds light on how this normally harmless bacterial species can evolve in response to environmental pressures such as antibiotic use, resulting in the rise of dangerous, drug-resistant strains. E. faecalis is one of the most abundant members of the human gut microbiome. Although these bacteria are usually benign, some strains have emerged that infect hospital patients and are resistant to antibiotics and disinfection protocols. However, the genetic adaptions that have allowed E. faecalis to transition from residing in the gut environment to infecting the human bloodstream remain unclear. Here, Daria Van Tyne and colleagues studied changes in the genome of E. faecalis strains that caused an outbreak of bloodstream infections in a Wisconsin hospital between 1984 and 1988. They compared the genomes of 62 outbreak strains isolated from patient blood samples with 27 non-outbreak-associated strains, and discovered that the outbreak strains acquired multiple mutations in a small set of genes, allowing them to better resist the host immune system and the use of antibiotics. The scientists confirmed that inducing these mutations in laboratory-grown E. faecalis enabled the bacteria to better resist antibiotics and innate immune defenses in human blood and a mouse model. Interestingly, Van Tyne et al. also observed a shift in mutation pattern that corresponded to the introduction of carbapenem antibiotics in 1987. The genetic variants identified could inform future studies on the transmission of drug-resistant E. faecalis in the hospital environment, they say.