Intraspecies Competition for Niches in the Distal Gut Dictate Transmission during Persistent Salmonella Infection

This is in Salmonella, but an interesting PLoS Path paper about niche competition using different tagged Salmonella strains and seeing how they compete with one another for gut colonization.

Abstract

In order to be transmitted, a pathogen must first successfully colonize and multiply within a host. Ecological principles can be applied to study host-pathogen interactions to predict transmission dynamics. Little is known about the population biology of Salmonella during persistent infection. To define Salmonella enterica serovar Typhimurium population structure in this context, 129SvJ mice were oral gavaged with a mixture of eight wild-type isogenic tagged Salmonella (WITS) strains. Distinct subpopulations arose within intestinal and systemic tissues after 35 days, and clonal expansion of the cecal and colonic subpopulation was responsible for increases in Salmonella fecal shedding. A co-infection system utilizing differentially marked isogenic strains was developed in which each mouse received one strain orally and the other systemically by intraperitoneal (IP) injection. Co-infections demonstrated that the intestinal subpopulation exerted intraspecies priority effects by excluding systemic S. Typhimurium from colonizing an extracellular niche within the cecum and colon. Importantly, the systemic strain was excluded from these distal gut sites and was not transmitted to naïve hosts. In addition, S. Typhimurium required hydrogenase, an enzyme that mediates acquisition of hydrogen from the gut microbiota, during the first week of infection to exert priority effects in the gut. Thus, early inhibitory priority effects are facilitated by the acquisition of nutrients, which allow S. Typhimurium to successfully compete for a nutritional niche in the distal gut. We also show that intraspecies colonization resistance is maintained by Salmonella Pathogenicity Islands SPI1 and SPI2 during persistent distal gut infection. Thus, important virulence effectors not only modulate interactions with host cells, but are crucial for Salmonella colonization of an extracellular intestinal niche and thereby also shape intraspecies dynamics. We conclude that priority effects and intraspecies competition for colonization niches in the distal gut control Salmonella population assembly and transmission.

Author Summary

Salmonella enterica serovars infect various mammalian hosts, causing disease ranging from self-limiting diarrhea to persistent systemic infections such as typhoid fever. Here we investigated the impact of an established intestinal S. Typhimurium population on fecal shedding in the presence of another challenging strain. This scenario arises during host-to-host transmission, as well as during chronic host-adapted infections when systemic Salmonella reseed the intestinal tract to be transmitted in feces. In a mouse model of persistent Salmonella infection, we found that distinct subpopulations formed in intestinal and systemic tissues. Expansion of the intestinal subpopulation was responsible for increases in fecal shedding, rather than increased secretion of systemic Salmonella. Furthermore, the Salmonella that initially colonized the gut excluded challengers from the cecum, colon, and feces. A challenging systemic strain could only be shed upon ablation of the established intestinal strain. This intraspecies colonization resistance requires Salmonella hydrogenase-mediated invasion of the distal gut and is maintained by the virulence effectors SPI1 and SPI2. We describe novel observations indicating that Salmonella virulence effectors that have been shown to subvert the host immune response and microbiota, also play a role in intraspecies competition for colonization of transmission niches.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004527

Advertisements
This entry was posted in Uncategorized. Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s