A Cornell University food scientist has co-authored a paper titled, "Genome sequencing reveals diversification of virulence factor content and possible host adaptation in distinct subpopulations of Salmonella" which focuses on research that will help accelerate the identification of Salmonella outbreak strains.  As this research is well-timed given recent stories in the news, we talked to Henk den Bakker, the publication's lead author from Martin Wiedmann's lab, to get more information about the study.

Read the full publication

Dr. Hank den Bakker:

The paper describes how you used various methods to describe differences between S. enterica species and subclades.  Why is an understanding of the population structure important for human health?

In the case of S. enterica there seems to be a strong correlation between population structure, that is groups of closely related strains, and the distribution of virulence factors such as gene clusters involved in attachment to host tissues, gene clusters involved in the metabolism of host specific carbon sources and cytotoxins.  Now that we know that these subgroups differ in virulence factor content we can start to look for phenotypes of these two subgroups, first with in vitro studies in tissue culture, followed by studies in animal models, and subsequently look for specific clinical presentations that are potentially associated with infections of Salmonella of these different subclades. A better understanding of the relation between Salmonella subgroups and the types of disease they cause will provide a better understanding of how these subgroups impact human health and the food industry.

Could you describe why whole genome sequencing was needed to reach your conclusions?

By choosing whole genome sequencing combined with de novo assembly of the genomes we were able to get unique information that allowed us to get the ‘whole picture’.  We used the sequence information of a large number of genes of these de novo assemblies to infer the population structure and at the same compare these genomes for the presence/absence of all the genes in the complete genome, which makes it possible to see which genes are present or absent in certain subpopulations.  This is in contrast to reference based assemblies, which can help to get a detailed picture of the population structure based on SNP data, but lacks the ability to discover novel genes that are not in the reference genome. With other methods (e.g., serotyping, PFGE, MLST, MLVA, microarray) we never could have obtained this amount of information.

What evidence did you see that some S. enterica serovars are adapted to human hosts?

We currently have no evidence that certain serovars (except for Typhi and Paratyphi A) are more adapted to the human host, however we now know that certain virulence factors that are found in known ‘human restricted’ serovars such as Typhi and Paratyphi A are found in a much wider variety of serovars. Future research is needed to determine if and how these virulence factors may affect the ability of these serovars to interact  with human hosts.

What did you learn about virulence factors and are there any practical implications from it?

One of the things we learned about the evolution of virulence factors in this study was that certain virulence factors, that were assumed to be specific for S. Typhi, were possibly already present in the most recent common ancestor of S. enterica and were very unlikely to be acquired by recent horizontal gene transfer. We also learned that the two clades of Salmonella differ in some virulence factors, and this may have implications for clinical symptoms associated with disease caused by Salmonella enterica.

People will be want to learn about S. Typhi and its relationships to other S. enterica.  Does that explain any of its history and how it originated.

One of the things we established in this study was a good list of candidates of the serovars that are most closely related to S. Typhi.  Research on pathogenicity and the evolutionary origin of S. Typhi has mainly focused on comparisons of various strains representing S. Typhi and a distantly related serovar, S. Typhimurium.  Comparative genomic research of S. Typhi with a wider range of Salmonella serovars, allowed us to identify its nearest relatives. Further comparative analysis of S. Typhi with its closely related serovars will give us a more precise picture of how S. Typhi evolved into the severe human pathogen it is now.