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Despite some dissenting voices, the notion that antimicrobial use in food animals has important implications for human health has gained strong support in recent years. However, it remains unclear how antimicrobial-resistant bacteria associated with food animals are linked to bacteria found in humans, and to what extent the spread of antimicrobial resistance is driven by bacterial cross-colonization versus horizontal gene transfer.

Our research team investigated how the genes conferring resistance to third-generation cephalosporins (3GC) are transmitted among commensal Escherichia coli strains from food animals to humans. Transmission may occur through human colonization by animal-associated bacteria, through the transfer of plasmids from animal bacteria to human bacteria, or through the movement of transposable elements between plasmids. To determine whether these processes are occurring, we looked for identical DNA sequences in the chromosomes or plasmids of both animal and human bacterial isolates. Although in a few cases we detected genetically identical 3GC-resistant strains in humans and food animals, most strains were genetically diverse, and surprisingly, there were no identical plasmids. [1, 2] However, the DNA sequences surrounding the blaCTX-M genes including transposable elements were identical in E. coli from humans and food animals. [2] (Figure 1) 

Furthermore, these identical DNA sequences were found not only in human commensal E. coli in the communities, but also in E. coli from urinary tract infections around Quito.[3] This finding seems to indicate that these resistance genes were dispersed in the community by transposons, or “jumping genes”, similar to those whose discovery resulted in Barbara McClintock being awarded the Nobel Prize in 1983.  The most likely explanation is that these transposable elements (such as IS26) mobilised the blaCTX-M genes among different plasmids, which subsequently transferred the genes among different E. coli strains within the intestines of humans and food animals. [2,3]

The role of transposable elements in the dissemination of antimicrobial resistance has previously been recognised, and they have been described as one of the major mobile genetic elements involved in this process. [4] However, our team did not anticipate their contribution to be so extensive.  

Knowing that third-generation cephalosporin (3GC) resistance is being transferred between human and food animal bacteria raises another question. In which direction does this transfer primarily occur: from food animals to humans, or from humans to food animals? This question is difficult to answer, especially in countries like Ecuador, where wastewater released into the environment is largely untreated and where regulations to control the use of antimicrobials are not enforced. 

Our team has observed that the presence of 3GC resistant E. coli is much higher in chicken intestines than in humans in Ecuador, which may indicate that food animals are the source of these resistant bacteria. These bacteria and genes from food animals may end up in humans through cross-contamination of food, for example when the same utensils are used to cut raw meat and vegetables that are consumed uncooked, or by eating raw eggs. [5) If this is true, it would reinforce the need to control antimicrobial resistance in animals with the same rigor applied in hospital settings. Also, our studies, together with those of others, highlight the important role of transposable elements in the transmission of antimicrobial resistance. Similar transposable elements have been found to be associated with genes conferring resistance to carbapenems, colistin, and other antimicrobials. [6, 7, 8, 9]

Figure 1.  Graphical representation of the DNA sequences found around the blaCTX-M gene, the gene responsible for resistance to 3rd generation cephalosporins in E. coli from chickens and humans. The transposable element is the IS26. 

Transposable elements are pieces of DNA that can move from one location to another within a genome, appearing to “jump” and insert themselves in different regions of the genome. These elements contain a gene coding for a transposase, which is an enzyme responsible for this process.

References

  1. Salinas L, Loayza F, Cárdenas P, Saraiva C, Johnson TJ, Amato H, Graham JP, Trueba G. Environmental Spread of Extended Spectrum Beta-Lactamase (ESBL) Producing Escherichia coli and ESBL Genes among Children and Domestic Animals in Ecuador. Environ Health Perspect. 2021 Feb;129(2):27007. doi: 10.1289/EHP7729.
  2. Salinas L, Cárdenas P, Graham JP, Trueba G. 2024. IS26 drives the dissemination of bla CTX-M genes in an Ecuadorian community. Microbiol Spectr 12:e02504-23.https://doi.org/10.1128/spectrum.02504-23.
  3. Guilcazo, D., Salinas, L., Chavez, C., Vasquez, K., Mendez, G. I., Price, L. B., … Trueba, G. (2025). Tracking blaCTX-M transmission through transposable elements in uropathogenic and commensal E. coli. Future Microbiology, 20(4), 287–293. https://doi.org/10.1080/17460913.2025.2459526.
  4. Partridge SR, Kwong SM, Firth N, Jensen SO 2018. Mobile Genetic Elements Associated with Antimicrobial Resistance. Clin Microbiol Rev 31:10.1128/cmr.00088-17.https://doi.org/10.1128/cmr.00088-17.
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  6. Kieffer N, Nordmann P, Poirel L. Moraxella species as potential sources of mcr-like polymyxin resistance determinants. Antimicrob Agents Chemother. 2017;61(6):e00129–17. doi: 10.1128/AAC.00129-17.
  7. Tacão M, Araújo S, Vendas M, et al. Shewanella species as the origin of blaOXA-48 genes: insights into gene diversity, associated phenotypes and possible transfer mechanisms. Int J Antimicrob Agents. 2018;51(3):340–348. doi: 10.1016/j.ijantimicag.2017.05.014.
  8. Sheppard AE, Stoesser N, Wilson DJ, Sebra R, Kasarskis A, Anson LW, Giess A, Pankhurst LJ, Vaughan A, Grim CJ, Cox HL, Yeh AJ; Modernising Medical Microbiology (MMM) Informatics Group; Sifri CD, Walker AS, Peto TE, Crook DW, Mathers AJ. Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC. Antimicrob Agents Chemother. 2016 May 23;60(6):3767-78. doi: 10.1128/AAC.00464-16. PMID: 27067320; PMCID: PMC4879409.
  9. Cifuentes SG, Graham J, Trueba G, Cárdenas PA. Hi-C untangles the temporal dynamics of the children’s gut resistome and mobilome, highlighting the role of transposable elements. mBio. 2025 Sep 10;16(9):e0113425. doi: 10.1128/mbio.01134-25. Epub 2025 Aug 12. PMID: 40793781; PMCID: PMC12421864.