title: A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile.
abstract: In the last decade, Clostridium difficile infection (CDI) has reached an epidemic state with increasing incidence and severity in both health care and community settings. Vancomycin is an important first-line therapy for CDI, and the emergence of resistance would have significant clinical consequences. In this study, we describe for the first time a vanB2 vancomycin resistance operon in C. difficile, isolated from an Australian veal calf at slaughter. The operon was carried on an ~42-kb element showing significant homology and synteny to Tn1549, a conjugative transposon linked with the emergence and global dissemination of vancomycin-resistant enterococci (VRE). Notably, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly as a result of an aberrant vanRB gene. As observed for other anaerobic species of the animal gut microbiota, C. difficile may be a reservoir of clinically important vancomycin resistance genes. IMPORTANCE In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile.
authors.affiliation: Microbiology and Immunology, School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Knight
authors.affiliation: Microbiology and Immunology, School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Grace O
authors.initials: GO
authors.lastname: Androga
authors.affiliation: Microbiological Diagnostic Unit Public Health Laboratory and Doherty Centre for Applied Microbial Genomics, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Ballard
authors.affiliation: Microbiological Diagnostic Unit Public Health Laboratory and Doherty Centre for Applied Microbial Genomics, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Howden
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Riley
keywords: Clostridium difficile infection; antimicrobial resistance; mobile genetic element; vanB