TheKlebsiella pneumoniae teroperon 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 ter operon, a genetic locus that confers tellurite oxide (K 2 TeO 3 ) 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 ROS-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 genes required to resist K 2 TeO 3 − and polymyxin B-induced stress, which suggested that K 2 TeO 3 -induced stress is experienced at the bacterial cell envelope. Finally, we confirmed that K 2 TeO 3 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 stress tolerance factor, therefore explaining its role in enhancing fitness in the gut and bladder.