TheKlebsiella pneumoniae teroperon enhances stress tolerance

Abstract

AbstractHealthcare-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 theteroperon, a genetic locus that confers tellurite oxide (K2TeO3) resistance, is associated with infection in colonized patients. Rather than enhancing fitness during infection, theteroperon 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 theteroperon 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 theteroperon to identify genes required to resist K2TeO3− and polymyxin B-induced stress, which suggested that K2TeO3-induced stress is experienced at the bacterial cell envelope. Finally, we confirmed that K2TeO3disrupts the Kp cell envelope, though these effects are independent ofter. Collectively, the results from these studies indicate a novel role for theteroperon as stress tolerance factor, therefore explaining its role in enhancing fitness in the gut and bladder.