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Development of enhanced methods for outbreak investigation and source attribution of Salmonella. - OZ0347

The Salmonella strain collection held by APHA is a unique and irreplaceable resource of national and international importance. Maintaining a representative collection of well characterised field and reference Salmonella enterica isolates fulfils the need to conserve reference strains for quality control, development of new typing schemes and source that provides a historic context for prospective studies aimed at understanding this important zoonotic pathogen. Furthermore, the application of new low-cost high-throughput technological approaches to study archived strain collections provides the opportunity to retrospectively analyse old collections providing fresh insights into the epidemiology, transmission and disease patterns. A case in point is the opportunity provided by the emergence of next-generation sequencing technology that has in the last few years made whole genome sequencing (WGS) of thousands of bacterial isolates financially viable.

In collaboration between the APHA, the Wellcome Trust Sanger Institute (WTSI) and PHE, we propose to take a methodical approach to evaluate the potential for retrospective analysis of the APHA Salmonella strain collection. The isolates span over 20 years and the majority are of serotypes that have zoonotic potential. Thus investigating this collection in detail will provide data and context relevant not only to animal health, but also human health. The massive strain collection and related epidemiological and spatio-temporal data will be scrutinised using statistical, Bayesian and phylogenetic methods which will then be used to inform selection of strains for comparative WGS to investigate the genetic properties of key Salmonella strains that are associated with their emergence and decline within certain livestock sectors and environmental niches. DNA based methods have been recommended to replace serotyping for strain discrimination. Sequencing a comprehensive background collection of Salmonella isolates of different serovars will facilitate the development of MLST typing scheme for routine use at APHA, which supplemented by even more discriminatory sequence-based typing methods based on entire genomes will increase strain discrimination and provide a clearer picture of long-term transmission.

The proposed study will provide:

(1) Context for future control programmes and potentially identify genetic markers for low- cost surveillance tests to identify potentially significant new strains at an early stage.

(2) This work will generate algorithms, validated by the sequence data that can be used to select representative strains, allowing a rationalisation of current strain storage and consequent cost savings for selection of representative strains from future surveillance.

(3) Work on the genetic stability of strains during different storage conditions will lead to optimisation of long-term storage and maintenance of strains in a manner that minimises losses in viability and genetic change making them more valuable to Government and commercial interests for future work.

(4) The findings will also feed into Defra components of future EFSA/ECDC initiatives on molecular typing of zoonotic pathogens, particularly in replacement of the reference laboratory serotyping of Salmonella spp. with WGS based typing by defining MLST derived clonal complexes and replacement of the current reference laboratory methods such as phage typing and MLVA/PFGE with SNP based phylogenies for strain resolution.
Objective 01 - In silico analysis: Assessment and analysis of the full collection of epidemiological metadata to inform sequencing studies and strain selection

Objective 02 - Microbiological: Triage of Salmonella stock cultures

Objective 03 - Molecular studies and whole genome sequencing

Objective 04 - Sequence data storage
Time-Scale and Cost
From: 2014

To: 2017

Cost: £535,308
Contractor / Funded Organisations
A H V L A (Animal Health and Veterinary Laboratories Agency - AHVLA)
Animal Diseases              
Animal Health              
Public Health              
Fields of Study
Animal Health