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.