Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization by .

UNLABELLED

Gastrointestinal (GI) colonization by is 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 for GI 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 () confirmed colonization defects in each of the three strains. Additionally, deletion of reduced bile tolerance , while complementation restored both bile tolerance and colonization ability . 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 gene resulted 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 classical strains use both shared and strain-specific strategies to colonize the mouse GI tract.

IMPORTANCE

is a common cause of difficult-to-treat infections due to its propensity to express resistance to many antibiotics. For example, carbapenem-resistant (CR-Kp) has been named an urgent threat by the United States Centers for Disease Control and Prevention. Gastrointestinal colonization of patients with has been linked to subsequent infection, making it a key process to control in prevention of multidrug-resistant infections. However, the bacterial factors which contribute to colonization are not well understood. Additionally, individual strains exhibit large amounts of genetic diversity, begging the question of whether some colonization factors are strain-dependent. This study identifies the enteric colonization factors of 3 classical strains using transposon mutant screens to define a core colonization program for as well as detecting strain-to-strain differences in colonization strategies.