This is a match-making section for OHAMR Call for proposals 2026.
H - Human Health
A - Animal Health E - EnvironmentAntimicrobial food residues; Acceptable Daily Intake; maximum Residue Limit
We are looking for centres that would like to work on any aspect of the evaluation of ADI/MRLs for antimicrobials in food. This could be Galleria mellonella, mouse model or ex vivo gut testing of the lowest dose of antimicrobials that can induce AMR/dysbiosis. It could be policy translation. Oiur work untill the present: In our first experiment, we found that a single dose of one-tenth of the EMA ADI dose of ciprofloxacin could select for de novo ciprofloxacin resistance in a Galleria mellonella model of chronic Klebsiella pneumoniae infection [18]. We did not test lower doses meaning that the MSC may be lower than this. Using a Streptococcus pneumoniae infection model of G. mellonella, we then found that 1/10th of the EMA ADI dose of erythromycin could induce de novo erythromycin resistance in S. pneumoniae [1]. Likewise, we found that 1/10th the EMA ADI dose of trimethoprim could induce trimethoprim resistance in a chronic E. coli infection of G. mellonella [2]. We then developed a murine model of chronic K. pneumoniae gut colonization [3]. The mice were given ADI and 1/10th ADI doses of enrofloxacin jellies daily. We found that enrofloxacin resistance emerged in K. pneumoniae in both groups receiving enrofloxacin but not the controls . Most recently, we have found similar results in humans. Using a randomised controlled trial design, we found that healthy volunteers randomized to daily ADI doses of ciprofloxacin, had significant increases in the ciprofloxacin MICs as well as fairly profound alterations to their gut microbiomes. The abundance of 179 taxa was significantly altered, as was the activity of 26 metabolic pathways [4]. References 1. Baranchyk Y, Gestels Z, Van den Bossche D, et al. Effect of erythromycin residuals in food on the development of resistance in Streptococcus pneumoniae : an in vivo study in Galleria mellonella. PeerJ 2024; 12:e17463. 2. Macleod JK, Gestels Z, Abdellati S, Vanbaelen T, Kenyon C, Manoharan-Basil SS. Determination of the De Novo Minimum Selection Concentration of Trimethoprim In Vivo for Escherichia coli Using Galleria mellonella: A Pilot Study. Microorganisms 2024; 13. 3. Gestels Z, Torfs B, Manoharan-Basil S, Kenyon C. “Acceptable” concentrations of enrofloxacin in food lead to reduced enrofloxacin susceptibility in a mouse model of gastrointestinal Klebsiella pneumoniae . Microbiol Spectr 2025; 4. Manoharan-Basil S, Gestels Z, Abdellati S, et al. Concentrations of ciprofloxacin in food defined as safe alter the gut microbiome and ciprofloxacin susceptibility in humans: an interventional clinical study. Sci Rep 2025; 15:34908.
We hypothesize that subinhibitory amoxicillin, CIP and tetracycline concentrations can induce or select for antimicrobial resistance in E. coli. We further hypothesize that these MSC values are below current MRL/ADI values. As a result, we hypothesize that the antimicrobial residues in food products, can induce or select for antimicrobial resistance in commensal and pathogenic bacteria. In this proposal, we aim to determine the lowest concentration of amoxicillin, CIP and tetracycline that can induce or select for antimicrobial resistance in E. coli in vitro and in vivo. Ultimately, we aim to establish safe ADI/MRLs that neither induce nor select for AMR. This will be accomplished through 5 specific objectives: 1. To determine the E. coli in vitro MSCdenovo for amoxicillin, ciprofloxacin and tetracycline and the MSCselect for ciprofloxacin 2. To determine the E. coli in vivo MSCdenovo for amoxicillin, ciprofloxacin and tetracycline and the MSCselect for ciprofloxacin in G. mellonella 3. To establish the E. coli MSCdenovo for ciprofloxacin and tetracycline in a mouse model 4. To establish the E. coli MSCdenovo for ciprofloxacin and tetracycline in an ex vivo human gut simulation model 5. To establish the E. coli MSCdenovo for ciprofloxacin and tetracycline in the human gastrointestinal tract
Submitted on 2026-01-12 07:51:49
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