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    • Consistent with the sporadic reports in China characterizati

    2018-11-14

    Consistent with the sporadic reports in China, characterization of the blaKPC-2- and blaNDM-bearing plasmids recovered from CRE in this study indicated that IncX3 conjugative plasmids carrying blaNDM is the major gene involved in dissemination of blaNDM among clinical CRE strains (Yang et al., 2014, 2015; Zhang et al., 2016). Although other conjugative plasmids were also involved in the transmission of blaNDM, the core structure of such mobile elements remains highly similar, suggesting that horizontal transfer of such mobile elements is the major mechanism responsible for emergence and rapid transmission of blaNDM. Compared to blaNDM, blaKPC-2-bearing plasmids were structurally more divergent, as blaKPC-2-bearing plasmids of various types and sizes were detectable in both K. pneumoniae and E. coli. However, the major mobile element that harbored blaKPC-2 was also found to be highly conservative, suggesting that this mobile element plays an important role in the emergence and transmission of blaKPC-2 among clinical CRE strains. The fact that the blaKPC-2-bearing plasmids in K. pneumoniae were less conjugative (35% were conjugative), but such plasmids in E. coli could undergo conjugation in most cases, suggests that these plasmids most likely emerged in K. pneumoniae, and were transmitted to E. coli and other bacterial species through conjugation. In conclusion, this study reported the first nationwide surveillance of CRE in China, a largest scale of CRE surveillance that have ever been reported. Essential information obtained from this study include: 1) blaNDM and blaKPC-2 were the major carbapenemase genes harbored by clinical CRE strains, with blaKPC-2 being more prevalent in K. pneumoniae and blaNDM being more prevalent in E. coli; 2) ST11 was the dominant type of CRKP, while ST131, ST167 and ST410 were the dominant types of CREC; 3) Polymyxins remained effective for K. pneumoniae and E. cloacae, while a number of neomycin sulfate are still effective for treatment of E. coli infections; 4) IncX3 plasmid was the major type of plasmid mediating transmission of blaNDM among clinical CRE strains, whereas plasmids harboring blaKPC-2 were more diverse in structure; 5) regardless of the structural diversity of plasmids harboring carbapenemase genes, the core structures of mobile elements containing blaNDM and blaKPC-2 were highly conservative; 6) the horizontal transfer of core structure of mobile elements carrying blaNDM and blaKPC-2 responsible for the transmission of these two carbapenemase genes in clinical CRE in China.
    Financial Support This study was funded by grants provided by the National Basic Research (973) Program of China (2013CB127200) and Collaborative Research Fund from Research Grant Council (C7038-15G and C5026-16G).
    Conflicts of Interest
    Author Contribution
    Acknowledgements
    Introduction The recent West African Ebola virus (EBOV) outbreak was the largest outbreak in the history of Ebola virus disease (EVD) with >28,600 confirmed infections and over 11,300 fatalities (WHO Situation Report, March 2016). This dramatic health crisis was in part facilitated by the lack of licensed medical countermeasures. Following the WHO declaration of the outbreak as a Public Health Emergency of International Concern, clinical studies of Ebola vaccine candidates were accelerated (Pavot, 2016), including rVSV-ZEBOV (recombinant vesicular stomatitis virus-vectored Ebola vaccine). As part of the WHO-led VSV-Ebola consortium (VEBCON) we conducted a phase I trial to test rVSV-ZEBOV in 30 healthy subjects using three dosage levels (3×105, 3×106 and 2×107 plaque forming units (PFU). The vaccine subsequently proceeded into a phase III trial (Ebola ça suffit!) demonstrating high efficacy in reduction of human-to-human transmission following rVSV-ZEBOV immunization (Henao-Restrepo et al., 2017). The priority licensing process is currently underway with anticipated licensure in 2017. Nevertheless, no human immunological correlate of protection exists and mechanisms of immune responses elicited by rVSV-ZEBOV remain incompletely understood.