<i>Klebsiella pneumoniae</i> evolution in the gut leads to spontaneous capsule loss and decreased virulence potential

In hospitalized patients, gut colonization by the bacterial pathogen <i>Klebsiella pneumoniae</i> (<i>Kp</i>) is a major risk factor for the development of infections. The genome of <i>Kp</i> varies across isolates, and the presence of certain virulence genes is associated with the ability to progress from colonization to infection. Here, we identified that virulence genes encoding capsule and lipopolysaccharide, which normally protect bacteria from the immune system, are disrupted by mutations during murine gut colonization. These mutations occurred frequently in some isolates of <i>Kp</i> but not others, and these virulence gene mutants from the gut were defective in causing infections. An analysis of 245 human gut isolates demonstrated that this capsule loss also occurred in patients. This work highlights that mutations that decrease virulence occur during gut colonization, the propensity for these mutations differs by isolate, and that stability of virulence genes is important to consider when assessing infection risk in patients.