Genomic Epidemiology of Escherichia coli in Human Blood-Stream Infections

Publication Type:
Thesis
Issue Date:
2021
Full metadata record
Blood-stream infections (BSI) are associated with high mortality and morbidity world-wide. The most common aetiological agent of these infections is 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪. The rise of multidrug resistant (MDR) 𝘌. 𝘤𝘰𝘭𝘪 is a major concern in clinical medicine and needs to be monitored for implementation of infection control strategies. The misuse of antimicrobials in clinical treatment, and as growth promotors in food-producing animals, is a key component of the rapid evolution of MDR 𝘌. 𝘤𝘰𝘭𝘪. MDR organisms spread antimicrobial resistance and virulence factors by lateral gene transfer via mobile genetic elements (MGEs). Despite this, there is limited knowledge of the origins and underlying mechanisms of BSI MDR 𝘌. 𝘤𝘰𝘭𝘪 infections in Australia. We conducted genomic epidemiological analyses of 𝘌. 𝘤𝘰𝘭𝘪 from human blood-cultures collected from a Sydney teaching hospital. The collection was dominated by 𝘌. 𝘤𝘰𝘭𝘪 causing community onset BSI, with clones carrying a plethora of virulence and antimicrobial resistance genes. Clinical class 1 integrons associated with IS26 were identified in a number of sequence types (ST), indicating that they are important drivers of evolution and spread of clinically important antimicrobial resistance genes. We identified IncFII-IncFIB plasmids in the majority of our collection. A number of STs harboured ColV like IncFII plasmids, carry a number of important virulence traits, were also identified. We observed a novel ST, ST8196, that clustered with globally disseminated 𝘌. 𝘤𝘰𝘭𝘪 ST131 isolates. We also identified an emerging ST, ST38, that exhibited resistance to a broad range of clinical beta-lactamases that have been identified in a number of pandemic 𝘌. 𝘤𝘰𝘭𝘪 isolates. Our study provides evidence that 𝘌. 𝘤𝘰𝘭𝘪 BSIs in Australia have a reservoir of antimicrobial resistance and virulence determinants that are potentially circulating not only in the community and hospital settings but across agricultural settings. These genes are not only present to clinical settings but can circulate within different ecosystems potentially via plasmids or other MGEs. Our findings also reveal that there are specific antimicrobial resistance genes such as ESBLs that are found in dominant 𝘌. 𝘤𝘰𝘭𝘪 clones in both humans and food producing animals. This is likely to occur due the overuse of antimicrobials in human and animal settings that is driving the increase in antimicrobial resistance among bacteria that cause diseases. It is therefore essential to rigorously monitor these infections to help manage the global problem of antimicrobial resistance, and to reduce or prevent disease outbreaks.
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