The Klebsiella pneumoniae Operon Enhances Stress Tolerance.

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 operon, a genetic locus that confers tellurite oxide (KTeO) resistance, is associated with infection in colonized patients. Rather than enhancing fitness during infection, the 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 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 operon to identify the genes that are required to resist KTeO-induced and polymyxin B-induced stress, which suggested that KTeO-induced stress is experienced at the bacterial cell envelope. Finally, we confirmed that KTeO disrupts the Kp cell envelope, though these effects are independent of . Collectively, the results from these studies indicate a novel role for the operon as a stress tolerance factor, thereby explaining its role in enhancing fitness in the gut and bladder.