Abstract
Monophasic Salmonella 4,[5]:12:i:- are a major public health problem because they are one of the top five Salmonella serotypes isolated from clinical cases globally and because they can carry resistance to multiple antibiotics. A total of 811 Salmonella 4,[5]:12:i:- and S. Typhimurium whole genome sequences (WGS) were generated. The various genetic lesions causing the Salmonella 4,[5]:12:i:- genotype were identified and assessed with regards to their distribution in the population of 811 Salmonella 4,[5]:12:i:- and S. Typhimurium isolates, their geographical and temporal distribution, and their association with non-human sources. Several clades were identified in the population structure, and the largest two were associated almost exclusively with a short prophage insertion and insertion of a mobile element carrying loci encoding antibiotic and mercury resistance. IS26-mediated deletions and fljB point mutants appeared to spread clonally. 'Inconsistent' Salmonella 4,[5]:12:i:- isolates associated with specific, single amino acid changes in fljA and hin were found in a single clade composed of water, shellfish, and avian isolates. Inclusion of isolates from different case clusters identified previously by PFGE validated some of the clusters and invalidated others. Some wgMLST clusters of clinical isolates composed of very closely related isolates contained an isolate(s) with a different genetic lesion, suggesting continuing mobility of the implicated element responsible. Such cases may need to be left out of epidemiological investigations until sufficient numbers of isolates are included that statistical significance of association with sources is not impaired. Non-human sources were frequently found in or near clinical case clusters. Prospective surveillance and WGS of non-human sources and retrospective analysis by WGS of isolates from existing culture collections provides data critical for epidemiological investigations of food- and waterborne outbreaks.
Highlights
Foodborne bacteria originate in animal and environmental niches, are amplified or lost during the processing of animals into food, and are introduced into human populations from food and water [1,2,3]
Typhimurium were obtained from Canadian provincial public health laboratories, FoodNet Canada, the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), the Canadian Food Inspection Agency (CFIA), Agriculture Canada, and provincial agriculture, veterinary, and animal health laboratories according to the selection criteria previously described [19]
We previously found SNPbased Maximum-Likelihood trees to be highly concordant with whole genome multi-locus sequence typing (wgMLST) UPGMA trees [19] and consider this to provide validation for use of the UPGMA dendrograms and Minimum Spanning Tree (MST) based on them in this work. wgMLST clusters were defined for this manuscript as groups of isolates that were distinguishable from the background of isolates in the UPGMA dendrogram or within ~10–12 alleles of each other [27] in BioNumerics wgMLST analysis
Summary
Foodborne bacteria originate in animal and environmental niches, are amplified or lost during the processing of animals into food, and are introduced into human populations from food and water [1,2,3]. The composition of bacterial populations infecting humans is not static, but frequently follows a pattern of establishment, rise to prominence, and subsequent decline. Typhimurium from disruptions in production of the second phase flagellar antigen locus (fljAB hin) associated with deletions, interruptions, or point mutations affecting all or part of this locus [8,9,10]. S. Typhimurium and Salmonella 4,[5],12:i:- populations appear to be in a dynamic state, with the monophasic variant either continuing to arise from S. Typhimurium re-acquiring a functional second-phase antigen locus [12]. Characterizing the multiple changes that disrupt the second-phase antigen locus may have practical value in surveillance, in outbreak and trace-back investigations, in public health risk assessments, and in developing interventions to reduce transmission of the organism through the food chain
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