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Research Themes Infectious diseases

Microbiome: The Dynamics of Infection

SBKB [doi:10.1038/sbkb.2012.160]
Technical Highlight - September 2013
Short description: A combination of systems approaches reveals how Salmonella displaces commensal gut bacteria to establish infections.

During the time-course of Salmonella infection, populations of host bacteria decrease, specific sugars change in abundance, and host inflammation is readily apparent through use of multiple omics technologies. Figure courtesy of Joshua Adkins.

Gastrointestinal infection by Salmonella enterica is a common form of food poisoning and a considerable public health concern. However, its pathogenic mechanism has been difficult to study in animal models, and there is little information on how Salmonella inoculation affects the endogenous microbiome. While commensal microbiota are known to serve a protective function—a phenomenon known as colonization resistance—the relevant interactions between resident and pathogenic bacteria are not clearly understood.

Now, Adkins and colleagues (Program for the Characterization of Secreted Effector Proteins) describe a combination of systems approaches that reveals how these pathogens compete with and displace commensal gut bacteria during infection. Using a mouse strain that is susceptible to gastrointestinal infection (unlike most research strains), the authors show that Salmonella enterica serovar Typhimurium induces inflammation and exploits the associated detrimental effects on the commensal gut population.

Mice were orally inoculated with Salmonella, and fecal samples collected over the course of infection were subjected to genomic, proteomic, glycomic and metabolomic analyses to monitor changes in organismal populations, sugars, metabolites and the host response concurrently.

Intestinal inflammation was revealed by changes in host immune factor expression, and an increase in proteins derived from Salmonella was accompanied by a concomitant decrease in microbiota-specific proteins, suggesting that the infection stimulates an immune response that disrupts the commensal population. Reciprocal changes in the bacterial populations were confirmed by 16s rDNA sequencing, which showed that Salmonella proliferates at the expense of multiple endogenous microorganisms. The combined changes in gut environment and its resident bacterial populations alter the metabolite profile of the intestine, as evidenced by the accumulation of sugars such as lactose and melibiose, which are readily digested by commensal enterics, but poorly metabolized by Salmonella. Conversely, Salmonella proteins involved in ethanolamine metabolism were observed, consistent with the pathogen's capacity for anaerobic growth, an advantage not shared by its fermentative competitors. Salmonella also profits from the altered environment by consuming fucose, which becomes more abundant in the infected gut.

This novel 'pan-omics' approach reveals that a complex network of interdependent changes in both bacterial populations and gut environment determines the success of Salmonella infection, and clearly illustrates how concurrently monitoring multiple parameters can provide the global view required to elucidate dynamic biological processes.

Beth Moorefield

References

  1. B.L. Deatherage Kaiser et al. A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection.
    PLoS ONE 8, e67155 (2013). doi:10.1371/journal.pone.0067155

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Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health