Tentative colistin epidemiological cut-off value for Salmonella spp
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Published on: July 21, 2023
Yvonne Agersø1, Mia Torpdahl, Camilla Zachariasen
1National Food Institute, Technical University of Denmark, Lyngby, Denmark. yvoa@food.dtu.dk
Abstract:
The objective of this research was to determine minimal inhibitory concentration (MIC) population distributions for colistin for Salmonella on subtype level. Furthermore, we wanted to determine if differences in MIC for colistin could be explained by mutations in pmrA or pmrB encoding proteins involved in processes that influence the binding of colistin to the cell membrane. During 2008-2011, 6,583 Salmonella enterica subsp. enterica isolates of human origin and 1931 isolates of animal/meat origin were collected. The isolates were serotyped, and susceptibility was tested towards colistin (range 1-16 mg/L). Moreover, 37 isolates were tested for mutations in pmrA and pmrB by polymerase chain reaction (PCR) and DNA sequencing. MIC distribution for colistin at serotype level showed that Salmonella Dublin (n=198) followed by Salmonella Enteritidis (n=1247) were less susceptible than "other" Salmonella serotypes originating from humans (n=5,274) and Salmonella Typhimurium of animal/meat origin (n=1794). MIC was ≤1 mg/L for 98.9% of "other" Salmonella serotypes originating from humans, 99.4% of Salmonella Typhimurium, 61.3% of Salmonella Enteritidis, and 12.1% of Salmonella Dublin isolates. Interestingly, Salmonella Dublin and Salmonella Enteritidis belong to the same O-group (O:1, 9,12), suggesting that surface lipopolysaccharides (LPS) of the cell (O-antigen) play a role in colistin susceptibility. The epidemiological cut-off value of >2 mg/L for colistin suggested by European Committee on Antimicrobial Susceptibility Testing (EUCAST) is placed inside the distribution for both Salmonella Dublin and Salmonella Enteritidis. All tested Salmonella Dublin isolates, regardless of MIC colistin value, had identical pmrA and pmrB sequences. Missense mutations were found only in pmrA in one Salmonella Reading and in pmrB in one Salmonella Concord isolate, both with MIC of ≤1 for colistin. In conclusion, our study indicates that missense mutations are not necessarily involved in increased MICs for colistin. Increased MICs for colistin seemed to be linked to specific serotypes (Salmonella Dublin and Salmonella Enteritidis). We recommend that Salmonella with MIC of >2 mg/L for colistin be evaluated on the serovar level.
Insights
Colistin resistance in Salmonella is linked to specific serotypes like Salmonella Dublin and Enteritidis, not necessarily mutations in pmrA or pmrB genes. Further evaluation of Salmonella with high colistin minimal inhibitory concentration (MIC) values is recommended.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Colistin is a critical antibiotic for treating multidrug-resistant Gram-negative infections.
- Salmonella species are significant foodborne pathogens with varying susceptibility to colistin.
- Understanding colistin resistance mechanisms in Salmonella is crucial for public health.
Purpose of the Study:
- To determine colistin minimal inhibitory concentration (MIC) population distributions for Salmonella at the subtype level.
- To investigate if mutations in pmrA or pmrB genes explain observed differences in colistin MICs.
- To assess the role of serotype and O-antigen in colistin susceptibility.
Main Methods:
- Analysis of 6,583 human and 1,931 animal/meat-origin Salmonella enterica subsp. enterica isolates collected between 2008-2011.
- Serotyping of isolates and antimicrobial susceptibility testing for colistin (1-16 mg/L).
- Polymerase chain reaction (PCR) and DNA sequencing to detect mutations in pmrA and pmrB in 37 selected isolates.
Main Results:
- Salmonella Dublin and Salmonella Enteritidis exhibited lower susceptibility to colistin compared to other serotypes.
- MICs ≤1 mg/L were observed in 12.1% of Salmonella Dublin and 61.3% of Salmonella Enteritidis isolates.
- No significant correlation was found between increased colistin MICs and mutations in pmrA or pmrB; all tested Salmonella Dublin isolates had identical sequences for these genes.
Conclusions:
- Increased colistin MICs in Salmonella are primarily associated with specific serotypes, notably Salmonella Dublin and Salmonella Enteritidis.
- The findings suggest that surface lipopolysaccharides (LPS), specifically the O-antigen, may play a role in colistin susceptibility.
- Further evaluation of Salmonella isolates with MIC >2 mg/L at the serovar level is recommended.
