Distinct increase in antimicrobial resistance genes among Escherichia coli during 50 years of antimicrobial use in livestock production in China

Abstract

Antimicrobial agents have been used in meat production for decades and its consumption is considered an key driver for the emergence and dissemination of antimicrobial resistance (AMR). However, large-scale studies on AMR changes in animal isolates since the introduction of antimicrobial usage remain scarce. We applied whole genome sequencing analysis to 982 animal-derived Escherichia coli collected in China from 1970s to 2019 and found increasing trends for the presence of numerous antimicrobial resistance genes (ARGs), including those conferring resistance to critically important agents for veterinary ( orfenicol and nor oxacin) and human medicine (colistin, cephalosporins, and meropenem). Extensive diversity and increasing complexity of ARGs and their associated mobile genetic elements (MGEs) such as plasmids were also observed. The plasmids, IncC, IncHI2, IncK, IncI, IncX and IncF played a key role as highly effective vehicles for disseminating ARGs. Correlation analysis also revealed an association between antimicrobial production and emergence of ARGs at a spatial and temporal level. Prohibiting or strictly curtailing antimicrobial use in animals will potentially negate the current trends of AMR as the bacterial genome is highly changeable and using different drugs of the same class, or even unrelated classes, may co-select for MGEs carrying a plethora of co-existing ARGs. Therefore, limiting or ceasing antimicrobial use in animals to control AMR requires careful consideration.

A Review of Current Bacterial Resistance to Antibiotics in Food Animals

“…Approximately 75% of antibiotics are not absorbed by the animals and are excreted from the body via feces and urine, which can directly contaminate and harm the surrounding environment ( Mackie et al, 2006 ; Zhou et al, 2022 ). Meanwhile, the misuse or overuse of antibiotics in animal production has led to diverse antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs), which can be transferred in animals and humans ( Martin et al, 2015 ; Zhang et al, 2015 ; He et al, 2020 ; Liu et al, 2022 ; Yang et al, 2022 ). There is increasing evidence that antibiotic resistance in humans is mainly related to the wide application of nontherapeutic antibiotics in animals ( Martin et al, 2015 ).…”

“…Multidrug-resistant (MDR) bacteria (including Staphylococcus spp., Enterococcus spp., Salmonella spp., E. coli , etc.) and ARGs were transferred to workers and residents in the surrounding environment via inhalation, thus, posing the risk of diseases ( Bai et al, 2021 ; Jeżak and Kozajda, 2022 ; Yang et al, 2022 ).…”

Characterization of Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates That Cause Diarrhea in Sheep in Northwest China

“…Animals, particularly food animals, have long been recognized as important reservoirs for ESBL-producing E. coli isolates ( 21 ). However, little research has been reported about multiple-antibiotic- resistant E. coli in sheep.…”

“…We presumed that the ESBL gene-positive isolates were more likely to recruit the resistance genes than isolates without target ESBL genes. Considering that bla CTX-M-55 has become increasingly prevalent in ESBL-producing E. coli isolates of animal origin but is relatively rare in isolates of human origin, this finding might indicate that bla CTX-M-55 and a variety of drug resistance genes emerged and rose under antibiotic selective pressure in animal husbandry ( 21 ). Therefore, prohibiting or strictly curtailing antimicrobial use in animal husbandry is urgently needed to address the increasing threat of antimicrobial resistance.…”

The Molecular Mechanism of Chloramphenicol and Thiamphenicol Resistance Mediated by a Novel Oxidase CmO in Sphingomonadaceae

“…The misuse and overuse of antibiotics, as the key driving force in the evolution and propagation of antibiotic resistance genes (ARGs), has caused ecological and human health risks, attracting the global attention (1)(2)(3). As the selection pressure posed by antibiotics was not strictly specific, long-term exposure to single or several antibiotics, especially those used widely and extensively, could accelerate the co-evolution of multiple ARGs (4)(5)(6). Amphenicol antibiotics, include chloramphenicol (CAP), its congener thiamphenicol (TAP) and florfenicol.…”