Abstract：
BACKGROUND: Vancomycin is frequently used as a last line of defence against infections due to multidrug-resistant Staphylococcus aureus (S. aureus). A recent finding described the acquisition of vancomycin-resistant S. aureus strains by the integration of an enterococcal plasmid containing the vanA operon into the S. aureus chromosome via homologous recombination involving a specific integration site called locus L2.
METHODS: To characterise all mechanisms of acquisition of vanA, this study analysed the 15 706 S. aureus genomes to look for vanA and described its genetic environment.
RESULTS: A complete vanA operon was found in 25 S. aureus strains isolated from 12 patients, including nine co-isolated with vancomycin-resistant Enterococcus strains. VanA was found within transposon Tn1546-like elements on 17 plasmids and eight chromosomes. VanA might be acquired through conjugation of enterococcal and staphylococcal plasmids, transposition of Tn1546 carrying vanA and plasmid integration into the chromosome. Further, L2 was detected in 2087 genomes (13.3%) of S. aureus strains across different continents. Six potential chromosomal hotspots for integration of the entire vanA-containing enterococcal plasmid were identified by homologous recombination via L2.
CONCLUSIONS: These findings suggest that the recently described scenario in a New York patient could be reproduced anywhere. Surveillance of this possibility is mandatory, especially in patients with vancomycin-resistant Enterococcus infection or colonisation.
METHODS: To characterise all mechanisms of acquisition of vanA, this study analysed the 15 706 S. aureus genomes to look for vanA and described its genetic environment.
RESULTS: A complete vanA operon was found in 25 S. aureus strains isolated from 12 patients, including nine co-isolated with vancomycin-resistant Enterococcus strains. VanA was found within transposon Tn1546-like elements on 17 plasmids and eight chromosomes. VanA might be acquired through conjugation of enterococcal and staphylococcal plasmids, transposition of Tn1546 carrying vanA and plasmid integration into the chromosome. Further, L2 was detected in 2087 genomes (13.3%) of S. aureus strains across different continents. Six potential chromosomal hotspots for integration of the entire vanA-containing enterococcal plasmid were identified by homologous recombination via L2.
CONCLUSIONS: These findings suggest that the recently described scenario in a New York patient could be reproduced anywhere. Surveillance of this possibility is mandatory, especially in patients with vancomycin-resistant Enterococcus infection or colonisation.
摘要：
万古霉素经常被用作抵抗多药耐药金黄色葡萄球菌感染的最后一道防线。最近的发现描述了通过将含有vanA操纵子的肠球菌质粒经由涉及称为基因座L2的特定整合位点的同源重组(HR)整合到金黄色葡萄球菌的染色体中来获得万古霉素抗性金黄色葡萄球菌(VRSA)菌株。为了描述获得vanA的所有机制，我们分析了寻找vanA的金黄色葡萄球菌的15,706个基因组，并描述了其遗传环境。我们在从12名患者中分离出的25个金黄色葡萄球菌菌株中发现了完整的vanA操纵子，其中9个与VRE菌株共分离。在转座子Tn1546样元件中发现了VanA，在十七个质粒和八个染色体上。VanA可能是通过肠球菌和葡萄球菌质粒的结合获得的，携带vanA的Tn1546转座和质粒整合到染色体中。我们在不同大陆的2,087个金黄色葡萄球菌菌株基因组（13.3％）中检测到L2，并确定了六个潜在的染色体热点，用于通过HR通过L2整合整个含vanA的肠球菌质粒。这表明最近在纽约患者中描述的情况可以在任何地方再现。监视这种可能性是强制性的,特别是在VRSA和VRE感染或定植的患者中。
