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

ABSTRACT

Due to rapidly falling costs, whole genome sequencing (WGS) is becoming an essential tool in the surveillance of antimicrobial resistance (AMR) in Salmonella enterica. Although there have been many recent works evaluating the accuracy of WGS in predicting AMR from a large number of Salmonella isolates, little attention has been devoted to deciphering the underlying causes of disagreement between the WGS genotype and experimentally determined AMR phenotype. This study analyzed the genomes of six S. enterica isolates previously obtained from raw chicken which exhibited disagreements between WGS genotype and AMR phenotype. A total of five WGS false negative predictions toward ampicillin, amoxicillin/clavulanate, colistin, and fosfomycin resistance were presented in conjunction with their corresponding empirical phenotypic and/or genetic evidence of heteroresistance. A further case study highlighting the inherent limitations of WGS to detect the underlying genetic mechanisms of colistin heteroresistance was presented. These findings implicate heteroresistance as an underlying cause for false negative WGS-based AMR predictions in S. enterica and suggest that widespread use of WGS in the surveillance of AMR in food isolates might severely underestimate true resistance rates.