The mechanisms underlying the biological activity of metformin, a widely prescribed drug to treat type 2 diabetes, remain elusive. In a recent issue of Cell, Cabreiro et al. report that in C. elegans, metformin indirectly impacts lifespan by altering the methionine metabolism of its microbial partner E. coli (Cabreiro et al., 2013).
In a paper in BMC Biology Virk et al. show that Caenorhabditis elegans lifespan is extended in response to a diet of folate-deficient Escherichia coli. The deficiencies in folate biosynthesis were due to an aroD mutation, or treatment of E. coli with sulfa drugs, which are mimics of the folate precursor para-aminobenzoic acid. This study suggests that pharmacological manipulation of the gut microbiome folate status may be a viable approach to slow animal aging, and raises questions about folate supplementation.
The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal morphogenesis of C. albicans. In this addendum we discuss these findings in the contest of other described bacterial-fungal interactions and recent data suggesting a potentially synergistic relationship between these two species in the mouse gut as well. We suggest that E. faecalis and C. albicans promote a mutually beneficial association with the host, in effect choosing a commensal lifestyle over a pathogenic one.
Iron plays many critical roles in human biology, such as aiding the transport of oxygen and mediating redox reactions. Iron is essential for life, yet little is known about how iron is taken up into mitochondria to impact the labile iron pool. Iron deficiency is one of the most prevalent human nutrient-deficiency diseases in the world and is a major cause of anemia that affects >25% of the world's population, but unfortunately the current treatment (oral iron supplementation) is inefficient and has many side effects. A greater understanding of iron uptake, and discovery of molecules that aid in this process, may lead to more effective treatments for iron deficiency. In this study, we uncovered a unique and surprising role for an <i>Escherichia coli</i>-produced siderophore enterobactin (Ent) that facilitates iron uptake by the host, observed in both <i>C. elegans</i> and mammalian cells. Although siderophores are well-known Fe<sup>+3</sup> scavengers, this activity has previously been described to only benefit iron acquisition by bacteria, not the host. This unexpected function is dependent on the binding of Ent to the host's ATP synthase -subunit but is independent of other subunits of the ATP synthase. This finding marks a major shift regarding the role of this siderophore in the "iron tug-of-war" paradigm, which is often used to describe the fight between the bacteria and the host for this essential micronutrient. Instead, this study presents <i>E. coli</i> as a commensal "friend" that provides a molecule that supports the host's iron homeostasis. This work reveals a novel, beneficial role of a bacteria-generated molecule in aiding the host's iron homeostasis, and points to surprising new benefits from commensal bacteria.