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The genetic factors responsible for daptomycin non-susceptible Staphylococcus aureus isolates in Australia

van der Made, Abigail (2021) The genetic factors responsible for daptomycin non-susceptible Staphylococcus aureus isolates in Australia. Honours thesis, Murdoch University.

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Daptomycin (DAP) is used as a last-line antibiotic to treat S. aureus infections. However, there has been an increase in the number of publications reporting DAP non-susceptibility (DNS). Extensive research on DNS has identified an association with an elevated DAP minimum inhibitory concentration (MIC) and the acquisition of single nucleotide polymorphisms (SNPs) in specific genes.

In this study, the reported SNPs in nine different genes (asp23, asp23a, cls, dsp1, mprF, pgsA, rpoB, rpoC, and walK) were investigated in 171 DAP non-susceptible (DAP-NS) S. aureus genomes to establish whether these SNPs were correlated to a particular DAP MIC value. The genetic diversity of S. aureus isolates was also investigated to determine whether DNS was linked to one specific sequence type. Screening for other antimicrobial resistance genes was also conducted. Lastly, the genomes of ST22 DAP susceptible (DAP-S) and DAP-NS isolates were compared to identify any significant differences in the genes associated with DNS. The results in this study demonstrated DNS was not associated with one particular sequence type. DNS, however, was observed in a genetically diverse population (47 sequence types), which had no impact on the MIC value. The majority of isolates (61.8%, n = 102/165) had one of the previously reported SNPs (S295L, P314L, S337L, L341S, T345A/I, V351E, I420N, and L826F) in the mprF locus. These SNPs, however, were not associated with one particular DAP MIC value. A cross-resistant relationship was not identified in this study. Distinct differences between DAP-S and DAP-NS ST22 isolates was observed. DAP-NS isolates had a more genetically diverse mprF gene compared to DAP-S isolates. All DAP-S isolates did not contain any of the previously
reported SNPs in any of the genes, including mprF, supporting the role of these SNPs in DNS.

This study has indicated DNS is highly variable regarding the acquisition of SNPs in genes previously associated with DNS. Evidence provided by this study also suggests DNS is not a result of clonal expansion in Australia, as seen by the genetically diverse population in the study.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): Medical, Molecular and Forensic Sciences
Supervisor(s): Coombs, Geoffrey and Mowlaboccus, Shakeel
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