Whole genome sequence analysis of Avian Pathogenic E. coli to assess their potential as reservoirs of antimicrobial resistance and as potential zoonotic pathogens

University of Technology Sydney. Faculty of Science.Antimicrobial resistance (AMR) is a complex, global health challenge requiring a One Health framework, acknowledging the interconnectedness of human, animal and environmental microbiospheres, in order to understand its reservoirs, transfer mechanisms and evolution. is a model ‘One Health organism’ as it is a gastrointestinal commensal of diverse vertebrate species, a common contaminant of foodstuffs and natural environments, increasingly multidrug resistant (MDR) and a major human pathogen. Within humans, extraintestinal pathogenic . (ExPEC) cause severe disease, including urinary tract infections (UTIs) and blood sepsis. Similarly, avian pathogenic . (APEC), a subset of ExPEC, cause significant economic losses in the poultry sector. Despite known phylogenetic and genotypic similarities between the two, it is still not possible to define them with genomic data alone and their transit between poultry and humans is poorly characterised. Genomic data on Australian APEC in particular is lacking, hampering efforts to assess and mitigate their threat to human and animal health. Accordingly, we characterised the genomes of 95 Australian MDR APEC sourced from four Australian states. ST117 and clonal-complex 350 were abundant, however pandemic human ExPEC lineages also featured, including ST95, ST73 and ST131. Almost all strains carried large ColV-like virulence plasmids, however no strains carried genes conferring resistance to critically important antimicrobials (CIAs), such as carbapenems, extended-spectrum β–lactams, fluoroquinolones and colistin, except one exhibiting a fluoroquinolone-resistance associated mutation. This attests to the value of strict antimicrobial use regulations in food animals in Australia. One strain carried a novel variant of genomic island 1 (SGI1) named SGI1-B-Ec1. SGI1 is an integrative mobilisable element that confers resistance to five different classes of antimicrobials and may confer pathogenicity traits. It was originally characterised in outbreak strains of serovar Typhimurium, however SGI1-related elements (SGI1-REs) have been reported in diverse genera, some carrying CIA-resistance genes. The first identification of an SGI1-RE in . is alarming as it indicates other more clinically significant SGI1-REs may exist within Australian food-animals. Subsequently, high-throughput analysis of 455,632 bacterial genomes revealed previously undescribed SGI1-REs in . , , and . This data provides valuable insight into the current AMR status of Australian MDR APEC, as well as the spread and evolution of SGI1 and SGI1-REs within Gammaproteobacteriaceae. Large-scale, One Health-oriented genomic epidemiological studies are urgently required into APEC and bacterial populations more broadly to identify and mitigate their threat to human and animal health