Genomic analysis of uropathogenic Escherichia coli from hospital patients in Australia

Li, Dmitriy

Genomic analysis of uropathogenic Escherichia coli from hospital patients in Australia

Li, Dmitriy

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Publication Type:: Thesis
Issue Date:: 2023

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Field	Value	Language
dc.contributor.author	Li, Dmitriy
dc.date.accessioned	2023-09-27T02:26:19Z
dc.date.available	2023-09-27T02:26:19Z
dc.date.issued	2023
dc.identifier.uri	http://hdl.handle.net/10453/172312
dc.description	University of Technology Sydney. Faculty of Science.	en_US.UTF-8
dc.description.abstract	Extraintestinal pathogenic Escherichia coli (ExPEC) are the leading cause of urinary tract and bloodstream infections ventilator-associated pneumonia, neonatal meningitis, and wound infections. In Australia, urinary tract infections (UTIs) inflict economic losses of >$AUD909M annually through ~70,000 hospitalisations and ~2.6 million general practitioner presentations and are a major driver for antibiotic prescriptions. Here we characterised 426 urine-sourced isolates (2006-2011) from Orange Base Hospital, a rural hospital in NSW, Australia. Chapter 4 presents analyses on 336 urine-sourced isolates that were not selected for phenotypic antibiotic resistances. A total of 91 sequence types (STs) were identified, but pandemic ExPEC lineages ST73, ST127, ST95 and ST131 dominated the collection ¬(146/336). F virulence plasmids carrying cjrABC-senB virulence genes cargo were a feature of the collection (15 STs), representing almost 40% (131/336) of the collection whereas UPEC carrying ColV F virulence plasmids (present in 16 STs) were limited in isolation frequency (10.4%; 35 isolates). Class 1 integrons were another feature of the study (n=88; 26.2%). Chapter 5 presents analyses on a collection of trimethoprim resistant isolates (n=67) because trimethoprim has been an important first line antibiotic for treating UTIs for over 40 years. Co-occurrence of trimethoprim-resistance genes with genes encoding extended-spectrum β-lactamases (ESBLs), heavy metals and quaternary ammonium ions was a feature of these ExPEC. ST131 dominated the collection (19/67; 28.4%) of trimethoprim resistant isolates and most carried a class 1 integron. We expanded our study of ST131 to include all isolates with suitable metadata that were of Australian origin. The study, presented in Chapter 6, comprised 284 Australian ST131 E. coli isolates from clinical sources, food and companion animals, wildlife, and the environment. Of these, 169 carried a class 1 integron. Forty-one isolates (14 %) contained the complete class one integron-integrase intI1. Notably, 45 % isolates harboured a truncated intI1 (462-1014bp). Frequently, these truncations occurred due to the insertion of IS elements, potentially impacting the integrons' capacity to obtain and activate genes. The ST131 H30Rx isolates often carried an antimicrobial gene profile comprising aac(3)-IIa, aac(6)-Ib-cr, aph(3')-Ia, aadA2, blaCTX-M-15, blaOXA-1 and dfrA12. Notably, dual parC-1aAB and gyrA-1AB fluoroquinolone resistant mutations were identified in some clade A isolates and this finding requires further monitoring. Although ST131 is an intensively studied ExPEC ST a thorough phylogenomic investigation of ST131 of Australian origin with a One Health perspective was undertaken here. Our study strongly suggests cross-species movement of ST131 strains across diverse reservoirs including humans, gulls, and companion animals.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/172312/1/thesis.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2023 Dmitriy Li
dc.rights	au.edu.uts.lib/cph
dc.title	Genomic analysis of uropathogenic Escherichia coli from hospital patients in Australia	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Extraintestinal pathogenic Escherichia coli (ExPEC) are the leading cause of urinary tract and bloodstream infections ventilator-associated pneumonia, neonatal meningitis, and wound infections. In Australia, urinary tract infections (UTIs) inflict economic losses of >$AUD909M annually through ~70,000 hospitalisations and ~2.6 million general practitioner presentations and are a major driver for antibiotic prescriptions. Here we characterised 426 urine-sourced isolates (2006-2011) from Orange Base Hospital, a rural hospital in NSW, Australia. Chapter 4 presents analyses on 336 urine-sourced isolates that were not selected for phenotypic antibiotic resistances. A total of 91 sequence types (STs) were identified, but pandemic ExPEC lineages ST73, ST127, ST95 and ST131 dominated the collection ¬(146/336). F virulence plasmids carrying cjrABC-senB virulence genes cargo were a feature of the collection (15 STs), representing almost 40% (131/336) of the collection whereas UPEC carrying ColV F virulence plasmids (present in 16 STs) were limited in isolation frequency (10.4%; 35 isolates). Class 1 integrons were another feature of the study (n=88; 26.2%). Chapter 5 presents analyses on a collection of trimethoprim resistant isolates (n=67) because trimethoprim has been an important first line antibiotic for treating UTIs for over 40 years. Co-occurrence of trimethoprim-resistance genes with genes encoding extended-spectrum β-lactamases (ESBLs), heavy metals and quaternary ammonium ions was a feature of these ExPEC. ST131 dominated the collection (19/67; 28.4%) of trimethoprim resistant isolates and most carried a class 1 integron. We expanded our study of ST131 to include all isolates with suitable metadata that were of Australian origin. The study, presented in Chapter 6, comprised 284 Australian ST131 E. coli isolates from clinical sources, food and companion animals, wildlife, and the environment. Of these, 169 carried a class 1 integron. Forty-one isolates (14 %) contained the complete class one integron-integrase intI1. Notably, 45 % isolates harboured a truncated intI1 (462-1014bp). Frequently, these truncations occurred due to the insertion of IS elements, potentially impacting the integrons' capacity to obtain and activate genes. The ST131 H30Rx isolates often carried an antimicrobial gene profile comprising aac(3)-IIa, aac(6)-Ib-cr, aph(3')-Ia, aadA2, blaCTX-M-15, blaOXA-1 and dfrA12. Notably, dual parC-1aAB and gyrA-1AB fluoroquinolone resistant mutations were identified in some clade A isolates and this finding requires further monitoring. Although ST131 is an intensively studied ExPEC ST a thorough phylogenomic investigation of ST131 of Australian origin with a One Health perspective was undertaken here. Our study strongly suggests cross-species movement of ST131 strains across diverse reservoirs including humans, gulls, and companion animals.

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http://hdl.handle.net/10453/172312