Elucidating the factors that define host species ranges of Salmonella enterica serovars. / Hayward, Matthew.

2013. 247 p.

Research output: ThesisDoctoral Thesis

Unpublished

Documents

Abstract

Salmonella enterica is an important zoonotic pathogen of clinical and veterinary significance. The species is divided into seven subspecies; subspecies 1, enterica, is further divided in to over 1530 serovars based on different epitopes of two surface antigens. Clinical and veterinary isolations of Salmonella are frequently typed to the serovar level of classification. This epidemiological data shows that some serovars are isolated from distinct subsets of species.

In this study I have focused on two serovars, S. Derby and S. Mbandaka, which are frequently isolated from distinct subsets of livestock species in the UK. The majority of S. Derby isolations are from pigs and turkeys, whereas the majority of S. Mbandaka isolations are from cattle and chickens. To begin to identify potential mechanisms of host adaptation, I sequenced two strains of each serovar and compared their nucleotide sequences and functional annotations. This lead to the discovery of a new Salmonella pathogenicity island, SPI-23, in the chromosome sequence of S. Derby, that I go on to show is regulated in a tissue specific manner in a porcine IVOC model. Mutagenesis of the most highly up-regulated gene within SPI-23, potR, generated unique phenotypes that have enabled me to posit a role for SPI-23 in tropism to porcine jejunum.

To interrogate the role of metabolite utilisation in constraining colonisation of certain niches, I performed high-throughput phenotyping using Biolog phenotypic microarray technology, at ambient and body temperatures, under aerobic and anaerobic conditions. This, along with other phenotypic studies, lead me to propose a partitioned niche model between host adaptation in the case of S. Derby and adaptation to persistence in the environment on soybean based feed in the case of S. Mbandaka.

To identify the contribution of an environment composed of a complex set of metabolites to host adaptation, I produced genome-scale metabolic reconstructions for both serovars. The models were confronted with metabolites found in porcine colon and jejunum; these I identified through metabolomics of gut sections using NMR. These models were used to observe which transport and secondary metabolic reactions contribute most to the incorporation of biomass by S. Derby and S. Mbandaka when in a porcine host.

Finally I relate the findings of these studies to a representative population of isolates, for which I have produced a phylogenetic reconstruction. I discovered two distinct lineages of S. Derby each with a distinct set of genotypes and phenotypes. I postulate that one lineage is adapted to turkeys and environmental persistence, and the other adapted to pathogenicity in pigs. I also show that S. Mbandaka is clonal in the UK, and is adapted to growth in soybean based feeds, at ambient temperatures and is adapted to environmental persistence.
Original languageEnglish
QualificationPh.D.
Awarding Institution
Supervisors/Advisors
Thesis sponsors
  • Eng & Phys Sci Res Council EPSRC
  • Veterinary Laboratories Agency
Award date1 Jan 2014
Publication statusUnpublished - 2013
This open access research output is licenced under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

ID: 18197018