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Study Suggests Epidemic Salmonella Strain Rarely Swapped Between Animal, Human Populations

NEW YORK (GenomeWeb News) – A study appearing online today in Science suggests that a strain of Salmonella involved in a global epidemic of multi-drug resistant infections passes back and forth between humans and animal sources quite rarely.

An international team led by investigators at the Wellcome Trust Sanger Institute did genome sequencing on hundreds Salmonella Typhimurium isolates collected from humans and animals in Scotland over more than two decades. The group also sequenced another 111 isolates of the same Salmonella Typhimurium strain from other parts of the world.

As it turned out, sequences from isolates taken from animals and humans largely clustered into distinct groups, the researchers found, each containing somewhat different drug resistance gene profiles. In particular, human pathogens tended to show more pronounced genetic diversity within antimicrobial resistance genes, underscoring an apparent lack of extensive intermingling with pools of Salmonella Typhimurium that infect animals.

"Our data provide a very simple message, challenging the established view that local animals are the predominant source of Salmonella infections in Scotland," senior author Nicholas Thomson, a pathogen genomics researcher with the Sanger Institute, said in a statement. "This finding will reinvigorate discussions on the sources of antibiotic-resistant Salmonella infections in humans in other environments."

The Salmonella Typhimurium designation refers to isolates from the Salmonella enterica sub-species enterica that belong to the Typhimurium serovar. For the current study, researchers focused on a form of Salmonella Typhimurium known as definitive type 104, or DT104 — a strain found in both humans and animals that contributed to a spate of multi-drug resistant Salmonella outbreaks around the world in the 1990s.

"The DT104 epidemic was important because of its widespread prevalence and perceived zoonotic nature," the study's authors noted, "as well as the high frequency of resistance to a wide range of commonly used antimicrobials."

To delve into the details of an arm of the DT104 epidemic and its proposed animal source, the group sequenced the genomes of 373 Salmonella Typhimurium DT104 isolates. These included 142 human and 120 animal isolates collected in Scotland over 22 years. The remaining DT104 isolates came from other parts of the world.

Using SNPs found across core sequences shared by the newly sequenced isolates and the DT104 reference genome, the team was able to tease apart phylogenetic relationships between Salmonella Typhimurium isolates.

That, in turn, offered clues about DT104's spread during the Scottish epidemic as well as the relative genetic diversity of animal and human isolates collected from the same locales.

"For the first time we've determined in detail and on a large scale how Salmonella strains taken from humans and animals in the same setting and over the same time period relate to each other," the study's first author Alison Mather, a post-doctoral researcher at the Sanger Institute, said in a statement.

Results from their analysis revealed elevated genetic diversity amongst human isolates and their antimicrobial resistance genes compared with isolates collected from animals in the same areas, consistent with the notion that animal and human infections in the region may have stemmed from different sources.

In particular, the group pointed to the possibility that the Salmonella DT104 isolates spread between humans may have hitchhiked to Scotland on imported foods or with the unwitting help of international travelers.

Even so, those involved in the study noted that more research is needed to test that theory and emphasized that findings from the analysis do not warrant a lax view of potential exposures to microbes found in animal populations.

"This finding in no way undermines the importance of prudent antimicrobial use in all species," Royal Veterinary College researcher Stuart Reid, a co-author on the study, said in a statement. "But our study does demonstrate that greater effort needs to be focused on understanding the natural history of the pathogens and on identifying the major sources of resistance in our global ecosystems."