Klebsiella pneumoniae (Kp) is an important cause of healthcare-associated infections, which increase patient morbidity, mortality, and hospitalization costs. Kp frequently colonizes the gut, and colonization is associated with subsequent urinary tract infection, bacteremia, and pneumonia. Our previous studies have identified a tellurite-resistance (ter) operon as strongly associated with infection. The ter operon is present in a subset of clinically important bacterial pathogens, wherein it has been shown to confer resistance to the toxic compound tellurite oxide. Tellurite oxideis extremely rare; thus, it is unlikely that resistance is clinically relevant, although it is a robust selective media additive for Kp containing the ter operon. In other bacterial systems, the ter operon has been suggested to play a role in resistance to stresses that are potentially encountered during gut colonization; however, the relationship between the ter operon and gut colonization has not been directly tested. Additionally, the role of the ter operon in stress resistance has not been assessed in Kp. To characterize the role of the ter operon, we compared a terC mutant to an isogenic wild-type strain. Next, we analyzed ter locus-encoding Kp plasmids to determine the genetic independence of the ter operon. Finally, we show that the ter operon is necessary for gut colonization using a murine model of gut colonization, and that this effect is alleviated upon disruption of the endogenous gut microbiome by antibiotics. Furthermore, our preliminary data suggest that the necessity of the ter operon during gut colonization is dependent on the composition of the gut microbiome. Together, these data indicate a novel role for the ter operon as a gut colonization factor. This work represents a substantial advancement in our molecular understanding of Kp pathogenesis and gut colonization directly relevant to Kp infections in healthcare settings.
