The human interactome and molecular mimicry

The human interactome

Our human genes continually express hundreds of proteins and metabolites.  At the same time, the microbes in our bodies express millions of their own proteins and metabolites. Because they are created in a common space, it is inevitable that many of these microbial compounds interact with those created by our own bodies. The sum of these host/microbe metabolite interactions is referred to as the human interactome. Human metabolism is directly altered by these interactions. For example, the medication acetaminophen is metabolized differently depending on the presence or absence of particular microbial metabolites in the blood.

2014-Proal-Toxicology.010Human and microbial metabolites interact so often that the interactome is almost impossible to quantify. Consider that the genome of the pathogen HIV codes for nine genes, which generate 19 proteins. According to Fu and team, there are 1,443 direct interactions (3,300 total interactions) between just these 19 proteins and metabolites in the human body. Now consider that the average bacterial genome codes for hundreds or sometimes thousands of proteins. Factor in the proteins created by viruses and phages, and it’s easy to see how the scope of the interactome is huge!

Molecular mimicry

The structures of many microbial proteins and metabolites are identical or very similar to those expressed by their human hosts. This complicates the interactome. For example, the pathways that allow the bacterium Escherichia coli and humans to break down glucose are very similar. Both organisms subsequently generate nearly identical protein byproducts as they metabolize the sugar molecule.

In many cases, the human superorganism may have significant trouble distinguishing the proteins and metabolites created by microbes from those recognized as “self.” This dysregulation is called “molecular mimicry.” Molecular mimicry appears to be extremely common.  For example, tens of thousands of protein-protein interactions have been documented between the genomes of the bacterial species Salmonella, Escherichia coli, Yersinia and the human genome.