Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization byKlebsiella pneumoniae

Abstract

Gastrointestinal (GI) colonization byKlebsiella pneumoniaeis a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. Thus, we aimed to study strain-specific requirements forK. pneumoniaeGI colonization by applying transposon insertion sequencing to three classical clinical strains: a carbapenem-resistant strain, an extended-spectrum beta-lactamase producing strain, and a non-epidemic antibiotic-susceptible strain. The transposon insertion libraries were screened in a murine model of GI colonization. At three days post-inoculation, 27 genes were required by all three strains for colonization. Isogenic deletion mutants for three genes/operons (acrA,carAB,tatABCD) confirmed colonization defects in each of the three strains. Additionally, deletion ofacrAreduced bile tolerancein vitro, while complementation restored both bile tolerancein vitroand colonization abilityin vivo. Transposon insertion sequencing suggested that some genes were more important for colonization of one strain than the others. For example, deletion of the sucrose porin-encoding genescrYresulted in a colonization defect in the carbapenemase-producing strain but not in the extended-spectrum beta-lactamase producer or the antibiotic-susceptible strain. These findings demonstrate that classicalK. pneumoniaestrains use both shared and strain-specific strategies to colonize the mouse GI tract.