The Klebsiella pneumoniae ter Operon Enhances Stress Tolerance
Manuscript Description
In this study, we aim to determine the molecular function of the ter operon. Previously, we demonstrated that the ter operon is highly associated with infection and a microbiome-dependent gut fitness factor. Our original studies exploring the association between ter and infection included patients with pneumonia and bacteremia, but not urinary tract infection (UTI). As Klebsiella is an important cause of UTI, we tested the role of ter during UTI and found that it is a bladder fitness factor. After exploration of several hypotheses that would explain how ter is a fitness factor in both the bladder and gut, we determined that it aids in stress tolerance. Therefore, ter responds to stressors that are found in both the gut and bladder. Then, we used a transposon library in a strain that does not encode ter to explore the molecular function of ter. We found several genes that influence cell envelope stability are necessary for resistance to tellurite oxide, which is the model cognate stress used to measure the biological activity of ter. Together, these data advance our knowledge of the biologically relevant function of ter.
Link
https://journals.asm.org/doi/10.1128/iai.00559-22
Abstract
Healthcare-acquired infections are a leading cause of disease in patients that are hospitalized or in long-term-care facilities. Klebsiella pneumoniae (Kp) is a leading cause of bacteremia, pneumonia, and urinary tract infections in these settings. Previous studies have established that the ter operon, a genetic locus that confers tellurite oxide (K2TeO3) resistance, is associated with infection in colonized patients. Rather than enhancing fitness during infection, the ter operon increases Kp fitness during gut colonization; however, the biologically relevant function of this operon is unknown. First, using a murine model of urinary tract infection, we demonstrate a novel role for the ter operon protein TerC as a bladder fitness factor. To further characterize TerC, we explored a variety of functions, including resistance to metal-induced stress, resistance to radical oxygen species-induced stress, and growth on specific sugars, all of which were independent of TerC. Then, using well-defined experimental guidelines, we determined that TerC is necessary for tolerance to ofloxacin, polymyxin B, and cetylpyridinium chloride. We used an ordered transposon library constructed in a Kp strain lacking the ter operon to identify the genes that are required to resist K2TeO3-induced and polymyxin B-induced stress, which suggested that K2TeO3-induced stress is experienced at the bacterial cell envelope. Finally, we confirmed that K2TeO3 disrupts the Kp cell envelope, though these effects are independent of ter. Collectively, the results from these studies indicate a novel role for the ter operon as a stress tolerance factor, thereby explaining its role in enhancing fitness in the gut and bladder.
Citation
TBD