Genomic epidemiology of third-generation cephalosporin-resistantEscherichia colifrom Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms

Abstract

AbstractControl measures are being introduced globally to reduce the prevalence of antibiotic resistant (ABR) bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in key opportunistic human pathogens such asEscherichia colion South American farms. Working with 30 dairy cattle farms and 40 pig farms across two provinces in central-eastern Argentina, we report a comprehensive genomic analysis of third-generation cephalosporin resistance (3GC-R) inE. coli. 3GC-R isolates were recovered from 34.8% (cattle) and 47.8% (pigs) of samples from faecally contaminated sites. Phylogenetic analysis revealed substantial diversity suggestive of long-term horizontal transmission of 3GC-R mechanisms. Despite this, mechanisms such as CTX-M-15 and CTX-M-2 were detected more often in dairy farms, while CTX-M-8 and CMY-2, and co-carriage of amoxicillin/clavulanate resistance and florfenicol resistance were more commonly detected in pig farms. This suggests different selective pressures of antibiotic use in these two animal types, particularly the balance of fourth-versus third-generation cephalosporin use, and of amoxicillin/clavulanate and florfenicol use. We identified the β-lactamase geneblaROBin 3GC-RE. coli, which has previously only been reported in the familyPasteurellaceae, including farmed animal pathogens.blaROBwas found alongside a novel florfenicol resistance gene –ydhC– also mobilised from a pig pathogen as part of a new plasmid-mediated composite transposon, which is already widely disseminated. These data set a baseline from which to measure the effects of interventions aimed at reducing on-farm ABR and provide an opportunity to investigate zoonotic transmission of resistant bacteria in this region.ImportanceLittle is known about the ecology of critically important antibiotic resistance among opportunistic human pathogens (e.g.Escherichia coli) on South American farms. By studying 70 farms in central-eastern Argentina, we identified that third-generation cephalosporin resistance (3GC-R) inE. coliwas mediated by mechanisms seen more often in certain species (pigs or dairy cattle) and that 3GC-R pigE. coliwere more likely to be co-resistant to florfenicol and amoxicillin/clavulanate. This suggests that on-farm antibiotic usage is key to selecting the types ofE. colipresent on these farms. 3GC-RE. coliwere highly phylogenetically variable and we identified thede novomobilisation of the resistance geneblaROB, alongside a novel florfenicol resistance gene, from pig pathogens intoE. colion a mobile genetic element that was widespread in the study region. Overall, this shows the importance of surveying poorly studied regions for critically important antibiotic resistance which might impact human health.