Oral Presentation BACPATH 2019

The Emergence of Pandemic Fluoroquinolone-Resistant Uropathogenic Escherichia coli Clones in Australia (#46)

Rhys T. White 1 2 3 , Brian M. Forde 1 2 3 , Leah W. Roberts 1 2 3 , Minh Duy Phan 2 3 , Kate M. Peters 2 3 , Darren J. Trott 4 , Justine S. Gibson 5 , Joanne L. Mollinger 6 , Ben A. Rogers 7 , Nouri L. Ben Zakour 8 9 , Amanda Kidsley 4 , Jan Bell 4 , John Turnidge 5 , Mark A. Schembri 2 3 , Scott A. Beatson 1 2 3
  1. Australian Centre for Ecogenomics, The University of Queensland, Brisbane, Queensland, Australia
  2. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  3. Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland, Australia
  4. Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  5. School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia
  6. Department of Agriculture and Fisheries, Biosecurity Sciences Laboratory, Brisbane, Queensland, Australia
  7. School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
  8. Westmead Institute for Medical Research, Sydney, NSW, Australia
  9. The University of Sydney, Sydney, NSW, Australia

 

Introduction:

Increasing resistance to fluoroquinolone antibiotics amongst uropathogenic Escherichia coli is of critical concern to public health. Resistance is mainly driven by the sequence type (ST)131 C2/H30Rx sub-lineage, however national surveillance in Australia reports increasing cases of both fluoroquinolone-resistant ST131 and ST1193. Despite this, limited genomic investigations have been undertaken nation-wide.

 

Methods:

Here, we analysed whole-genome sequence data of ST131 (n=183) and ST1193 (n=65) isolates collected across Australia between 2001-2014. Long-read sequencing of several isolates enabled the genomic context of genes encoding antimicrobial resistance and virulence to be determined. We contextualised our Australian dataset with well-characterised published genomes to investigate spatial clusters and lineage diversity.

 

Results:

Most ST131 isolates were from clade C (n=193, 92.3%) and contained mutations in gyrA and parC conferring fluoroquinolone resistance (FQR). In comparison, FQR in ST1193 is mediated by different mutations in the same chromosomal genes. Bayesian analysis predicted that fluoroquinolone-resistant ST131 and ST1193 emerged in 1987 and 1989 (respectively), coinciding with increased usage of fluoroquinolones worldwide. Acquisition of fitness and uropathogenicity genes likely primed ST131 for success before the development of FQR. Conversely, ST1193 is characterised by recombination of a 30.4 kb region encompassing the capsular biosynthesis genes causing a switch from the K5 to K1 capsular antigen, associated with altered host immune evasion. This capsule switch in an already FQR background enhanced virulence and is associated with expansion of the major ST1193 sub-lineage. In comparison, six group two capsular polysaccharides are present across ST131, with the K5 capsular antigen the most prevalent (n=96, 45.9%). ST1193 and ST131 share a genomic island inserted at tRNA-asnT carrying the same siderophore-dependent iron uptake systems and putative adhesins.

 

Conclusion:

ST131 and ST1193 have disseminated across Australia following the independent acquisition of mutations in genes conferring FQR. ST131 underwent massive population expansion following the acquisition of FQR in 1987, while recombination in the capsular region appears to have driven the expansion of FQR ST1193.