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Selection for florfenicol resistance at sub-MIC concentrations in Pasteurella multocida
Abigail Hughes1, Ludovic Pelligand1,2, Dan I Andersson3
1Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.
Abstract:
Antimicrobial resistance is a global threat to both human and animal health, and transfer of resistance between these spheres is recognised as a key concern for all species. Selection for resistance at sub-inhibitory antimicrobial concentrations has been characterised for some bacteria-antimicrobial combinations but there is little data from non-laboratory strains, and veterinary antimicrobials and bacterial species. Here, we demonstrate a minimum selective concentration of 0.06 mg/L (1/6 xMIC) for florfenicol in wild-type Pasteurella multocida, through competition experiments between a susceptible strain and a floR-resistant mutant. We also show that sub-inhibitory concentrations of florfenicol do not appear to significantly select for de novo resistance in P. multocida and present the challenges with adapting experimental protocols between bacterial species. These results have important implications for antimicrobial resistance selection at sub-inhibitory concentrations, method development for within-species differentiation in novel bacterial species, and application to policy regarding antimicrobial contamination in animal-feed.
Insights
Sub-inhibitory florfenicol concentrations can select for antimicrobial resistance in Pasteurella multocida at low levels. This study highlights challenges in developing resistance detection methods for veterinary bacteria.
Area of Science:
- Veterinary Microbiology
- Antimicrobial Resistance Research
- Molecular Biology
Background:
- Antimicrobial resistance (AMR) poses a significant global health threat, impacting both human and animal populations.
- The transfer of resistance genes between bacteria in different environments is a critical concern.
- Limited data exists on AMR selection by sub-inhibitory concentrations of veterinary antimicrobials in non-laboratory bacterial strains.
Purpose of the Study:
- To determine the minimum selective concentration (MSC) of florfenicol for Pasteurella multocida.
- To investigate whether sub-inhibitory florfenicol concentrations promote de novo resistance development.
- To identify challenges in adapting AMR experimental protocols across different bacterial species.
Main Methods:
- Competition experiments were conducted between a florfenicol-susceptible wild-type Pasteurella multocida strain and a floR-resistant mutant.
- Minimum Inhibitory Concentration (MIC) was determined for florfenicol against P. multocida.
- Sub-inhibitory concentrations were tested to assess selection for resistance.
Main Results:
- The minimum selective concentration for florfenicol in wild-type Pasteurella multocida was determined to be 0.06 mg/L (1/6 x MIC).
- Sub-inhibitory concentrations of florfenicol did not significantly select for the de novo development of resistance in P. multocida.
- Challenges were encountered when adapting experimental protocols for AMR selection studies between different bacterial species.
Conclusions:
- Low-level, sub-inhibitory concentrations of florfenicol can exert selective pressure for antimicrobial resistance in Pasteurella multocida.
- Developing standardized methods for detecting AMR in novel bacterial species requires careful consideration of inter-species protocol adaptation.
- Findings have implications for antimicrobial stewardship, policy on animal feed contamination, and AMR surveillance.
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