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Assessment of the global impact of MCR-1/MCR-3 mediated colistin resistance

Li, Mei 2023. Assessment of the global impact of MCR-1/MCR-3 mediated colistin resistance. PhD Thesis, Cardiff University.
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Colistin resistance mediated by mcr spread rapidly worldwide in only a few years. This thesis investigated factors influencing the colistin resistance transfer by conjugation for two of the most prevalent mcr variants - mcr-1 and mcr-3. Uniquely, the conditions carried out were to simulate real-life environmental conditions including conjugation temperatures, and the addition of colistin at mating. Furthermore, I used not only standard lab-based recipients (Escherichia coli J53) but significantly, wild-type isolates from different “one-health” sectors and presenting major clones/clades. Temperature and colistin did not significantly influence the conjugative frequency for mcr-1/-3. However, the genetic background of the recipient strains did have a significant effect on the transfer frequency. In addition, three mcr-1/-3 co-harbouring donors were included to examine whether there was a favourable transfer of different plasmids. Seemingly, each donor strain had a preference of which mcr plasmid to conjugate. The conjugation of mcr-3-harbouring IncHI2 plasmids produced unusual data and warranted further analysis. Plasmid pWJ1-mcr-3-IncHI2 was transferred to J53 and its frequency at 30℃ was significantly higher. All of the plasmids obtained at 30℃ were the same size as in donor strain, while plasmids identified at 37℃-42℃ showed significant differences to the original plasmid. These differences manifested as a fusion plasmid of pWJ1-mcr-3-IncHI2 with pWJ1-IncF, mediated by recombination at a homologous site of 5.4-kb; or a recombination plasmid of pWJ1-mcr-3-IncHI2 with pWJ1-IncF but only contained IncF replicons mediated by IS26 and IS3 Plasmid pWJ1-mcr-3-IncHI2 was further transferred into carbapenem-resistant strain YT3R at 30℃. YT3R harboured an IncHI2 plasmid, pYT3R-blaNDM-IncHI2. Two types of transconjugants were identified: a recombination plasmid of pWJ1-mcr-3-IncHI2 and pYT3R-blaNDM-IncHI2; and a fusion plasmid of pWJ1-mcr-3-IncHI2 and pWJ1-IncF mediated by IS15DI. Movement of blaNDM-ISCR1 was detected from pYT3R-blaNDM-IncHI2 to the fusion plasmid. Stability studies showed that blaNDM was rapidly lost yet mcr-3 was generally retained after a 24-day colistin-free treatment.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 19 July 2023
Last Modified: 19 Jul 2023 09:56

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