title: Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden.
abstract: We characterized clinically occurring and novel mutations in the β subunit of RNA polymerase in Clostridium difficile (CdRpoB), conferring rifamycin (including rifaximin) resistance. The Arg505Lys substitution did not impose an in vitro fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling of CdRpoB. In general, most mutations lacked in vitro fitness costs, suggesting that rifamycin resistance may in some cases persist in the clinic.
authors.affiliation: Department of Biology, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Uyen T
authors.initials: UT
authors.lastname: Dang
authors.affiliation: Department of Biology, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Idalia
authors.initials: I
authors.lastname: Zamora
authors.affiliation: Biomedical and Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Meridian, Idaho, USA.
authors.forename: Kirk E
authors.initials: KE
authors.lastname: Hevener
authors.affiliation: Department of Biology, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Sudip
authors.initials: S
authors.lastname: Adhikari
authors.affiliation: Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, USA.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biology, University of Texas at Arlington, Arlington, Texas, USA Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, USA Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USA jhurdle@ibt.tamhsc.edu.
authors.forename: Julian G
authors.initials: JG
authors.lastname: Hurdle
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000235:genetics*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics*; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D012294:Rifamycins / Q000494:pharmacology*; D000078262:Rifaximin
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases; D000078262:Rifaximin