Whole genome sequencing (WGS) fails to detect antimicrobial resistance (AMR) from heteroresistant subpopulation of Salmonella enterica

Zwe, Ye Htut; Chin, Seow Fong; Kohli, Gurjeet S.; Aung, Kyaw Thu; Yang, Liang; Yuk, Hyun‐Gyun

doi:10.1016/j.fm.2020.103530

Cited by 20 publications

(14 citation statements)

References 43 publications

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“…For example, one S. Cerro isolate (BOV_CERO_35_10-02-08_R8-2685) was reported to be phenotypically resistant to nine antimicrobials but did not possess any acquired AMR determinants known to produce this phenotypic AMR profile. A recent case study in which WGS and phenotypic methods were used to characterize Salmonella isolates from raw chicken identified numerous AMR genotype/phenotype discrepancies resulting in both false negative and false positive predictions for in silico methods This is a provisional file, not the final typeset article (Zwe et al, 2020). In this case study, the authors attributed these discrepancies to heteroresistant Salmonella subpopulations (i.e., a subpopulation of bacteria that exhibits a range of susceptibility to a particular antimicrobial).…”

Section: Limitations Of the In Silico Amr Methods Evaluation Presented Here And Considerations For Future Amr Monitoring Efforts Among LImentioning

confidence: 94%

Monitoring the Antimicrobial Resistance Dynamics of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing

Carroll

Buehler

Gaballa

et al. 2021

Preprint

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Livestock represent a possible reservoir for facilitating the transmission of the zoonotic foodborne pathogen Salmonella enterica to humans; there is also concern that strains can acquire resistance to antimicrobials in the farm environment. Here, we use whole-genome sequencing (WGS) to characterize Salmonella strains (n = 128) isolated from healthy dairy cattle and their associated environments on 13 New York State farms to assess the diversity and microevolution of this important pathogen at the level of the individual herd. Additionally, the accuracy and concordance of multiple in silico tools are assessed, including: (i) two in silico serotyping tools, (ii) combinations of five antimicrobial resistance (AMR) determinant detection tools and one to five AMR determinant databases, and (iii) one antimicrobial minimum inhibitory concentration (MIC) prediction tool. For the isolates sequenced here, in silico serotyping methods outperformed traditional serotyping and resolved all un-typable and/or ambiguous serotype assignments. Serotypes assigned in silico showed greater congruency with the Salmonella whole-genome phylogeny than traditional serotype assignments, and in silico methods showed high concordance (99% agreement). In silico AMR determinant detection methods additionally showed a high degree of concordance, regardless of the pipeline or database used (≥98% agreement between susceptible/resistant assignments for all pipeline/database combinations). For AMR detection methods that relied exclusively on nucleotide BLAST, accuracy could be maximized by using a range of minimum nucleotide identity and coverage thresholds, with thresholds of 75% nucleotide identity and 50-60% coverage adequate for most pipeline/database combinations. In silico characterization of the microevolution and AMR dynamics of each of six serotype groups (S. Anatum, Cerro, Kentucky, Meleagridis, Newport, Typhimurium/Typhimurium variant Copenhagen) revealed that some lineages were strongly associated with individual farms, while others were distributed across multiple farms. Numerous AMR determinant acquisition and loss events were identified, including the recent acquisition of cephalosporin resistance-conferring blaCMY- and blaCTX-M-type beta-lactamases. The results presented here provide high-resolution insight into the temporal dynamics of AMR Salmonella at the scale of the individual farm and highlight both the strengths and limitations of WGS in tracking zoonotic pathogens and their associated AMR determinants at the livestock-human interface.

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Section: Limitations Of the In Silico Amr Methods Evaluation Presented Here And Considerations For Future Amr Monitoring Efforts Among LImentioning

confidence: 94%

Monitoring the Antimicrobial Resistance Dynamics of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing

Carroll

Buehler

Gaballa

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Yet a gold standard remains out of reach due to discrepancies. A major source of these discrepancies is hetero-resistant Salmonella, which cannot be predicted for using current WGS software [51]. Thus, no primary diagnostic tool (including WGS) currently exists for MDR Salmonella, although recent improvements in automated precommercialized SIR technologies (FASTinov ® ) could lead to better predictive accuracies in the future [67].…”

Section: Discussionmentioning

confidence: 99%

“…Upon exclusion of the VME rates for streptomycin and sulfamethoxazole, said values increased to 0.89 and 0.97. Notably, the WGS-based genotyping methods used in the study did not account for attenuation mechanisms or reliably predict for underlying temporary genetic features (tandem repeats) present in subpopulations (heteroresistance) during phenotypic testing [51].…”

Section: Automated Whole Genome Sequencingmentioning

confidence: 99%

Recent Advances in the Detection of Antibiotic and Multi-Drug Resistant Salmonella: An Update

Hulme

2021

IJMS

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Antibiotic and multi-drug resistant (MDR) Salmonella poses a significant threat to public health due to its ability to colonize animals (cold and warm-blooded) and contaminate freshwater supplies. Monitoring antibiotic resistant Salmonella is traditionally costly, involving the application of phenotypic and genotypic tests over several days. However, with the introduction of cheaper semi-automated devices in the last decade, strain detection and identification times have significantly fallen. This, in turn, has led to efficiently regulated food production systems and further reductions in food safety hazards. This review highlights current and emerging technologies used in the detection of antibiotic resistant and MDR Salmonella.

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“…For example, one S. Cerro isolate (BOV_CERO_35_10-02-08_R8-2685) was reported to be phenotypically resistant to nine antimicrobials but did not possess any acquired AMR determinants known to produce this phenotypic AMR profile. A recent case study in which WGS and phenotypic methods were used to characterize Salmonella isolates from raw chicken identified numerous AMR genotype/phenotype discrepancies resulting in both false negative and false positive predictions for in silico methods ( Zwe et al, 2020 ). In this case study, the authors attributed these discrepancies to heteroresistant Salmonella subpopulations (i.e., a subpopulation of bacteria that exhibits a range of susceptibility to a particular antimicrobial).…”

Section: Discussionmentioning

confidence: 99%

Monitoring the Microevolution of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing

et al. 2021

View full text Add to dashboard Cite

Livestock represent a possible reservoir for facilitating the transmission of the zoonotic foodborne pathogen Salmonella enterica to humans; there is also concern that strains can acquire resistance to antimicrobials in the farm environment. Here, whole-genome sequencing (WGS) was used to characterize Salmonella strains (n = 128) isolated from healthy dairy cattle and their associated environments on 13 New York State farms to assess the diversity and microevolution of this important pathogen at the level of the individual herd. Additionally, the accuracy and concordance of multiple in silico tools are assessed, including: (i) two in silico serotyping tools, (ii) combinations of five antimicrobial resistance (AMR) determinant detection tools and one to five AMR determinant databases, and (iii) one antimicrobial minimum inhibitory concentration (MIC) prediction tool. For the isolates sequenced here, in silico serotyping methods outperformed traditional serotyping and resolved all un-typable and/or ambiguous serotype assignments. Serotypes assigned in silico showed greater congruency with the Salmonella whole-genome phylogeny than traditional serotype assignments, and in silico methods showed high concordance (99% agreement). In silico AMR determinant detection methods additionally showed a high degree of concordance, regardless of the pipeline or database used (≥98% agreement among susceptible/resistant assignments for all pipeline/database combinations). For AMR detection methods that relied exclusively on nucleotide BLAST, accuracy could be maximized by using a range of minimum nucleotide identity and coverage thresholds, with thresholds of 75% nucleotide identity and 50–60% coverage adequate for most pipeline/database combinations. In silico characterization of the microevolution and AMR dynamics of each of six serotype groups (S. Anatum, Cerro, Kentucky, Meleagridis, Newport, Typhimurium/Typhimurium variant Copenhagen) revealed that some lineages were strongly associated with individual farms, while others were distributed across multiple farms. Numerous AMR determinant acquisition and loss events were identified, including the recent acquisition of cephalosporin resistance-conferring blaCMY- and blaCTX–M-type beta-lactamases. The results presented here provide high-resolution insight into the temporal dynamics of AMR Salmonella at the scale of the individual farm and highlight both the strengths and limitations of WGS in tracking zoonotic pathogens and their associated AMR determinants at the livestock-human interface.

show abstract

Whole genome sequencing (WGS) fails to detect antimicrobial resistance (AMR) from heteroresistant subpopulation of Salmonella enterica

Cited by 20 publications

References 43 publications

Monitoring the Antimicrobial Resistance Dynamics of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing

Monitoring the Antimicrobial Resistance Dynamics of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing

Recent Advances in the Detection of Antibiotic and Multi-Drug Resistant Salmonella: An Update

Monitoring the Microevolution of Salmonella enterica in Healthy Dairy Cattle Populations at the Individual Farm Level Using Whole-Genome Sequencing

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