Sedative choice alters Klebsiella pneumoniae lung pathogenesis and dissemination

ABSTRACT Klebsiella pneumoniae makes up 85% of carbapenem-resistant Enterobacteriaceae, 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 widely used anesthetic induction agent propofol. Recent evidence obtained from rodent infection models indicates that propofol exposure can dramatically increase host susceptibility to microbial infections. Given that intensive care patients who are at a greater risk for K. pneumoniae lung infections are often given propofol during their hospitalization, we investigated the outcome of K. pneumoniae infections in mice briefly sedated with either propofol or ketamine/xylazine as a control. Propofol-sedated mice experienced more rapid dissemination from the lungs to secondary sites of infection, and their lungs exhibited more severe pathology. Based on these observations, we investigated bacterial factors involved in infection and dissemination in mice with propofol or ketamine/xylazine 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 characterized a mutant lacking the phospholipid retrograde trafficking chaperone MlaC and found that the degree of mutant attenuation was dependent upon the sedation method. These results highlight the importance of sedative choice when studying hospital-acquired microbial infections and suggest that sedation can influence the outcome of K. pneumoniae infection and dissemination in animal models.