Sedative choice alters Klebsiella pneumoniae lung pathogenesis and dissemination

Klebsiella pneumoniae make up 85% of Carbapenem-resistant Enterobacteriaceae (CRE), bacteria that have become an urgent threat to public health. K. pneumoniae is largely transmitted in healthcare settings, where inpatients and outpatients are often anesthetized with the ubiquitously-used anesthetic induction agent propofol. Recent evidence indicates that propofol exposure can dramatically increase host susceptibility to microbial infections. Given that intubated patients are often given propofol and are at risk for K. pneumoniae lung infections, we investigated the outcome of K. pneumoniae infections in mice briefly sedated with either propofol or ketamine/xylazine as control. Propofol-sedated mice experienced more rapid dissemination from the lungs to secondary sites of infection and developed more severe lung pathology. Based on these observations, we investigated bacterial factors involved in infection and dissemination in mice with and without propofol sedation using a high throughput insertion sequencing (INSeq) approach. We identified numerous novel potential virulence factors together with previously identified gene products, confirming the validity of our screen. We further identified insertion mutants with differing degrees of attenuation dependent upon sedation method. These results highlight the importance of sedative choice when studying hospital-acquired microbial infections and suggest that sedation can influence the arsenal of bacterial virulence factors required to promote K. pneumoniae infection and dissemination in animal models.