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Published on: March 24, 2023
Plasmid-Coded Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus from Food and Livestock in Germany
Tobias Lienen1, Mirjam Grobbel1, Bernd-Alois Tenhagen1
1German Federal Institute for Risk Assessment (BfR), Department of Biological Safety, 10589 Berlin, Germany.
Abstract:
Resistance of methicillin-resistant Staphylococcus aureus (MRSA) from food and livestock to last resort antibiotics such as linezolid is highly concerning, since treatment options for infections in humans might be diminished. Known mechanisms of linezolid resistance include point mutations in the 23S rRNA gene and in the ribosomal proteins L3, L4 and L22 as well as an acquisition of the cfr, optrA or poxtA gene. The objective of our study was to characterize antimicrobial resistance (AMR) determinants and phylogenetic relationships among linezolid-resistant (LR-) MRSA from food and livestock. In total, from more than 4000 incoming isolates in the years 2012 to 2021, only two strains from 2015 originating from pig samples exhibited linezolid resistance in the antimicrobial susceptibility testing with MICs of ≥8 mg/L. These LR-MRSA were characterized in detail by whole-genome sequencing and phylogenetic analyses using cgMLST. The LR-MRSA strains showed resistances to ten and eight different antibiotics, respectively. Both strains harbored plasmid-coded cfr genes mediating the linezolid resistance. The cfr genes showed identical sequences in both strains. In addition to the cfr gene, genes for phenicol and clindamycin resistance were detected on the respective plasmids, opening the possibility for a co-selection. The LR-MRSA differed distantly in the phylogenetic analyses and also to other MRSA from pig samples in the year 2015. In conclusion, the occurrence of LR-MRSA in food and livestock seems to be very rare in Germany. However, carriage of plasmids with linezolid resistance determinants could lead to further linezolid-resistant strains by horizontal gene transfer.
Insights
Two linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) strains from pigs were identified in Germany. These strains carried plasmid-borne cfr genes, conferring resistance to last-resort antibiotics and raising concerns for public health.
Area of Science:
- Veterinary Microbiology
- Antimicrobial Resistance
- Food Safety
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat to human health, particularly when resistant to last-resort antibiotics like linezolid.
- Mechanisms of linezolid resistance in MRSA include specific gene mutations (23S rRNA, L3, L4, L22) or acquisition of mobile genetic elements (cfr, optrA, poxtA).
- The emergence of linezolid-resistant MRSA (LR-MRSA) in food-producing animals necessitates understanding resistance determinants and epidemiology to prevent transmission and safeguard therapeutic options.
Purpose of the Study:
- To characterize antimicrobial resistance (AMR) profiles and phylogenetic relationships of LR-MRSA isolated from food and livestock.
- To identify the genetic mechanisms conferring linezolid resistance in these strains.
- To assess the prevalence and potential spread of LR-MRSA in the German food production sector.
Main Methods:
- Antimicrobial susceptibility testing was performed on over 4000 MRSA isolates from 2012-2021.
- Whole-genome sequencing (WGS) was employed for detailed characterization of identified LR-MRSA strains.
- Phylogenetic analysis using core genome multilocus sequence typing (cgMLST) was conducted to determine evolutionary relationships.
Main Results:
- Only two LR-MRSA strains were detected between 2012-2021, both isolated from pig samples in 2015.
- These strains exhibited resistance to multiple antibiotics and harbored identical plasmid-coded cfr genes responsible for linezolid resistance.
- Phylogenetic analysis revealed distinct lineages for these LR-MRSA strains, differing from other contemporary MRSA from pigs.
Conclusions:
- Linezolid-resistant MRSA appears to be rare in German food-producing animals based on this study's findings.
- The presence of plasmid-mediated cfr genes highlights the risk of horizontal gene transfer and the potential for future emergence of LR-MRSA.
- Continuous surveillance of AMR in livestock is crucial to monitor and mitigate the threat of antibiotic resistance in the food chain.
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