Friends or Frenemies?

This is a second paper from Host Cell and Microbe describing how mouse gut residing commensal microbe's metabolic end-product, succinate, fuels the virulence of pathogenic Citrobacter rodentium (C. rodentium).

This study, led by Vanessa Sperandio at UT Southwestern Medical Center, Dallas, analysed virulence factor expression in mouse C. rodentium, in presence of mouse gut commensal Bacteroides thetaiotaomicron (Bt). The authors have used C. rodentium disease model that mimics E. coli infection in humans.

It appears that the authors' initial objectives were to study the mechanisms by which gut commensals were driving virulence factor expression in pathogenic microbes and only later diverted their attention towards the role of succinate metabolism in this process.

First, the authors showed that presence of Bt enhances expression of several virulence factors in E. coli and in an in vitro culture.  

Similar results were observed with C. rodentium  culture.

Interestingly, this enhancement was not observed in cra mutant E. coli that is incapable of sensing sugar fermentation products, like succinate (however, the authors did not show similar results with cra mutant C. rodentium).

In vivo experiments with either wild-type C. rodentium or mutant strains showed that reconstitution of antibiotic treated mice with Bt could enhance C. rodentium pathogenicity. The authors reported that severity of infection with cra mutant C. rodentium  was attenuated, though not abolished, it appears (implying that C. rodentium showed cra-succinate independent virulence).

Still, analysis of sugar fermentation products in the day 2 post infected mice cecum showed that there was selective increase in succinate in presence of Bt or C. rodentium.

Finally, addition of succinate to E. coli culture could enhance expression of virulence factors in the wild-type but not in a cra mutant E. coli strain (again, the authors did not show similar results with cra mutant C. rodentium).

In summary, this study and another one from Justin Sonnenburg's lab, highlighted the potential detrimental role of gut commensals in fueling the virulence of pathogenic microbes. We are thinking that the term gut commensal implies friendly microbe, however occasionally those friendly microbes could involuntarily provide support to pathogenic ones.

David Usharauli