Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden

We characterized clinically occurring and novel mutations in the β subunit of RNA polymerase inClostridium difficile (Cd RpoB), conferring rifamycin (including rifaximin) resistance. The Arg505 Lys substitution did not impose anin vitro fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling ofCd RpoB. In general, most mutations lackedin vitro fitness costs, suggesting that rifamycin resistance may in some cases persist in the clinic.