Microbiology and Immunology, School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia.
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.
mSphere. 2016 Aug 10;1(4). doi: 10.1128/mSphere.00177-16. eCollection 2016 Jul-Aug.
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.
在过去的十年中，艰难梭菌感染（CDI）在医疗保健和社区环境中都呈现出发病率和严重程度不断增加的流行状态。万古霉素是治疗 CDI 的重要一线药物，而耐药性的出现将产生重大的临床后果。在这项研究中，我们首次描述了从澳大利亚小牛屠宰场分离的艰难梭菌中的一个 vanB2 万古霉素耐药操纵子。该操纵子位于一个约 42kb 的元件上，与 Tn1549 具有显著的同源性和基因排列顺序，Tn1549 是一种与万古霉素耐药肠球菌（VRE）的出现和全球传播相关的可转移转座子。值得注意的是，该艰难梭菌菌株在体外对万古霉素没有表现出任何敏感性降低（MIC，1mg/L），这可能是由于 vanRB 基因异常。与其他动物肠道微生物群的厌氧物种一样，艰难梭菌可能是临床重要的万古霉素耐药基因的储库。
在新抗菌药物开发缓慢的时代，万古霉素仍然是治疗艰难梭菌感染（CDI）的首选抗菌药物，CDI 是当今世界最重要的与医疗保健相关的感染。对万古霉素的耐药性的出现将对治疗 CDI 患者产生重大影响。在本文中，我们首次在艰难梭菌中描述了一整套万古霉素耐药基因。这些基因与与万古霉素耐药肠球菌（VRE）相关的基因非常相似，而 VRE 与该生物体的出现和全球传播有关。幸运的是，该艰难梭菌菌株在体外对万古霉素没有表现出任何敏感性降低（MIC，1mg/L），这可能是由于一个基因的微小差异。然而，这一观察结果表明，我们可能很快就会看到完全对万古霉素耐药的艰难梭菌菌株。
